Authors: Sarvesh Kumar Mishra, Tapojyoti Sanyal, Pritha Kundu, Rupesh Kumar, Dipanjan Ghosh, Gopal Chakrabarti, Nilabja Sikdar, Sayan Bhattacharya, Santanu Paul, Amlan Das
Categories: Review, Microplastics, Nanoplastics, Cancer, Tumor Microenvironment, NF-κB, PI3K/Akt/mTOR, Wnt/β-catenin, P53 signaling
Source: Molecular Cancer
Authors: Sarvesh Kumar Mishra, Tapojyoti Sanyal, Pritha Kundu, Rupesh Kumar, Dipanjan Ghosh, Gopal Chakrabarti, Nilabja Sikdar, Sayan Bhattacharya, Santanu Paul, Amlan Das
The widespread environmental pollution of microplastics (MPs) and nanoplastics (NPs) has become a major public health issue, with increasing evidence associating their bioaccumulation with cancer onset. This review offers a thorough examination of the etiological contributions of MPs/NPs in carcinogenesis, clarifying their mechanistic roles in in vitro, in vivo, and patient-derived evidences. Relevant studies were systematically identified and screened following the PRISMA 2020 guidelines to ensure methodological transparency and quality. We highlighted recent discoveries that emphasize the varied accumulation of MPs in several human cancer tissues, including lung, colorectal, gastric, cervical, breast, pancreatic, prostate and penile malignancies. These particles induce harmful biological effects by chronic inflammation, oxidative stress, genotoxicity, disturbance of lipid metabolism, and alteration of the tumor immunological microenvironment. Significantly, MPs/NPs disrupt various oncogenic signaling pathways, particularly NF-κB, PI3K/Akt/mTOR, Wnt/β-catenin, and p53, therefore facilitating tumor initiation, development, and metastasis. In vitro and in vivo studies have corroborated the carcinogenic potential of MPs/NPs, illustrating their capacity to cause cellular transformation, augment metastatic characteristics, and modify drug resistance pathways in cancer cells. Furthermore, the detection of MPs in human biological matrices, including blood, placenta, and tumor tissues, highlights direct human exposure and potential systemic effects. This review emphasizes the mechanistic insights with therapeutic significance, addressing current knowledge gaps in the field. Future research must prioritize biomarker identification, patient-centered investigations, therapeutic targeting, and the formulation of regulatory policies to alleviate the health hazards linked to microplastic exposure. Understanding the intricate relationship between MPs/NPs and cancer biology could facilitate the development of novel cancer prevention and management strategies related to environmental contamination.
The ongoing and extensive pollution of the environment, largely due to the unsustainable practices associated with plastic usage and disposal, has become increasingly critical in recent years. From 1950 to 2015, global production of plastic surged from 5 megatons to over 300 megatons. In 2015 alone, between 60 and 99 Mt of plastic ended up as waste, and projections suggest that by 2060, this number may rise to between 155 and 265 Mt each year [1]. Even though global plastic production has surged, many regions still have low recycling rates. For instance, in 2012, only 26.3% of plastic waste in all of Europe was recycled [2].
The most widely used and plentiful polymers in everyday life are PVC (Polyvinyl chloride), PS (Polystyrene), PP (Polypropylene), PET (Polyethene terephthalate), HDPE (high-density polyethene), and LDPE (low-density polyethene)(Fig. 1). About 75% of the plastic demand in Europe and approximately 90% of the demand worldwide [3]is met by these polymers. According to [4], half of these plastic products, which include packaging, plastic bags, and cutlery, are single-use items. Generally, the most prevalent plastic polymer found is polyethylene [3, 4].
Fig. 1Literature review of the microplastics for cancer. A: Bar diagram of the published documents about microplastics and cancer, B: Number of published documents about the different polymers for microplastics responsible for cancer
Plastics found in the environment can be categorised into five types based on their size, like nanoplastics (NP) (< 1 μm), microplastics[MP] (≥ 1 μm to < 5 mm), mesoplastics (≥ 5 mm to 5 cm), macroplastics (> 5–50 cm), and megaplastics (> 50 cm) [1]. Small-sized plastics are referred to as contaminants to the environment because of their tendency and magnitude of complexity, diversity, persistence, and accumulation [5]. Microplastics are fine fragments of plastic of approx. 1–5 mm in size [6–8]. These emerging contaminants are classified depending on their sizes, forms, shapes, sources, polymeric structures, and combinations. Microplastics are classified as primary and secondary microplastics. Primary MPs are produced during the manufacturing of different plastic materials; secondary microplastics are formed by the degradation and fragmentation of large plastic pieces [9, 10].
Considerable evidence showed that microplastics are worrisome emerging pollutants, executing detrimental impacts on ecosystems and human health. They can be found in diverse types of ecosystems and environments, including freshwater, estuaries, wetlands, oceans, mountains, soil, groundwater/surface water, and air [11, 12]. The presence of microplastics in the aquatic environment is a major concern because of their behemoth effects on aquatic ecosystems and food chains [11].
MPs are likely to be found in a wide range of environments, such as soil, air, freshwater, and the ocean [13]. Crucially, the accumulation of MPs in the food chain is one way that MPs can enter the human body. MPs have reportedly been found in human tissue and organs, as well as the digestive tracts of marine animals [14]. It has been demonstrated that consuming MPs can trigger an inflammatory reaction, affecting the gastrointestinal tract, disrupting gut microbes, damaging organs, and having considerable impacts on metabolism and reproduction [15]. Inhaling MPs can expose the body to harmful microbes, trigger chemical toxicity, and induce inflammation. MPs that encounter the skin can lead to cellular toxicity and local inflammation of the skin [16]. Humans begin consuming MPs at a young age [17, 18] and continue to do so throughout their lives [19, 20].
In young children, the average daily consumption of MPs from plastic infant feeding bottles was 1,580,000 particles, corresponding to an infant exposure 2600 times greater than adult consumption from water, food, and air combined [21]. In adults, MP exposure is estimated to be between 0.1 and 5 g/week [22]. In contrast, an unrelated study calculated that an adult’s annual MP consumption is between 48,000 and 52,000 MP, rising to 94,000–114,000 MP when considering all particles inhaled [23].
Microplastics have significant impacts on different environmental media. Microplastics are considered physical contaminants of the soil [24], capable of decreasing the bulk density of the soil [25]. Microplastics can impart new characteristics to soil surfaces, such as hydrophobicity. Certain contaminants, especially those that are hydrophobic, may accumulate on these particles and may remain stable for extended periods [26]. Microplastic particles have the potential to carry phytotoxic substances into the soil with them if they are already present in the microplastics before their arrival (for example, when added during the manufacturing process) [27]. The diversity of the soil biota, in particular the nitrogen-fixers, pathogens, and mycorrhizal fungi, is crucial for the physiological activities of plants [28, 29]. If soil structure is altered by microplastics, this may have an impact on microbial communities in the soil [30], which may have an impact on mineralisation rates and communities of symbionts that colonise roots. Recentstudies highlighted the significant impacts of microplastics on several aquatic species worldwide. The impact of MP on benthic marine and freshwater invertebrates, such as annelids, arthropods, ascidians, sea urchins, bivalve mollusks, and rotifers, is investigated [31]. A serious risk to human health arises from MPs found in seafood. A vital component of the human diet is seafood. There is a significant chance that MPs contamination of the digestive system will spread to other parts of the body. Two of the most popular routes by which MPs enter the human body are endocytosis and phagocytosis. According to in vitro experiments, MPs cause adverse cellular changes in fish and concentrate in the gills, stomachs, and metabolic systems of crabs [32, 33]. Additionally, MP exposure can lead to oxidative stress and cytotoxicity, thereby affecting tissues and organs. The toxicological effects of microplastics can impact fish populations and can affect fish harvesting and aquaculture activities [34–36].
The history of plastics is a narrative of scientific ingenuity, marked by a series of groundbreaking discoveries that have transformed material science. The journey began in 1839, when Eduard Simon, a German apothecary, first discovered polystyrene, a polymer that would later become a cornerstone of modern packaging and insulation materials [37]. This discovery set the stage for the development of synthetic polymers, with Alexander Parkes introducing Parkesine, the first manufactured plastic, in 1862, which was subsequently patented [38].
The evolution of plastics continued with the synthesis of polyvinyl chloride (PVC) in 1872 by German chemist Eugen Baumann, a versatile polymer later used in pipes, packaging, and numerous industrial applications. Polyethylene (PE), another ubiquitous plastic, was accidentally synthesized in 1898 by Hans von Pechmann, a German chemist, laying the foundation for the development of low-density polyethylene (LDPE) and high-density polyethylene (HDPE) [39]. These versatile materials would dominate consumer and industrial products in the decades that followed. By the early 20th century, advancements in polymer chemistry accelerated. Poly Lactic Acid (PLA), a biodegradable polymer derived from renewable sources like corn starch, was developed in the 1920s by Wallace Carothers, providing an early example of sustainable polymer design [40]. Polymethyl methacrylate (PMMA), known for its optical clarity and strength, was introduced in the 1930s by Rowland Hill and John Crawford, further expanding the range of plastic applications [41]. During the same era, Low-Density Polyethylene (LDPE) was first produced in 1933 by John C. Swallow and M.W. Perrin, followed by the first usable acrylic resin dispersion developed by BASF in 1934 [42]. The discovery of polyamide (PA), commonly known as Nylon, in 1935 by Wallace Carothers at DuPont, revolutionized the textile industry, providing a durable synthetic fiber that became a household name [42]. Shortly thereafter, polyurethane (PU) was developed in 1937 by Otto Bayer and his team at IG Farben, offering versatile applications in foams, coatings, and elastomers. The era of polymer innovation continued with the invention of Polyethylene Terephthalate (PET) in 1941 by John Rex Whinfield and James Tennant Dickson, a polymer now widely used in beverage bottles and textile fibers [43]. The commercialization of Polystyrene Foam (STYROFOAM™) by Ray McIntire in 1944 further demonstrated the adaptability of synthetic polymers for insulation and packaging [44]. By the 1950s, polymer science saw further advancements, with Polypropylene (PP) being discovered in 1951 by J. Paul Hogan and Robert Banks at Phillips Petroleum Company, a polymer known for its lightweight and chemical resistance. The decade concluded with the development of High-Density Polyethylene (HDPE) in 1953 by Karl Ziegler and Erhard Holzkamp, a durable plastic that remains widely used in packaging and piping .
The term “microplastics” was first coined in 2004 by Professor Richard Thompson of the University of Plymouth, marking a pivotal moment in environmental science as researchers began to recognize the pervasive presence of microscopic plastic particles in natural ecosystems. Notably, microplastics were first identified in human placenta samples, raising serious concerns about their potential impact on human health [18]. These polymers, once celebrated for their durability and versatility, have now become a global environmental challenge. As they degrade, they transform into microplastics, which persist in ecosystems, accumulate in water bodies, and infiltrate soil. These tiny particles pose a significant threat to marine life, terrestrial organisms, and human health, primarily due to their ability to absorb and transport toxic chemicals. The historical timeline of the evolution and impact of microplastics is comprehensively depicted in Fig. 2.
Fig. 2Schematic illustration of the timeline of the remarkable events on microplastic and its polymers
The frequent discovery of MPs(< 5 mm) in environmental media and human meals has raised worries about their contamination across the globe [45]. Microplastics (MPs) found in humans exhibit significant variation in size, shape, and type of polymers. Smaller particles, measuring less than 50 μm, are primarily located in internal organs such as the placenta and liver, while larger particles exceeding 100 μm, are more commonly found in fecal matter and skin samples [46]. Research has identified over 45 different types of polymers, with polypropylene (PP), polyethylene terephthalate (PET), and polyethylene (PE) being the most frequently observed [47]. Notably, some unique polymers like polyoxymethylene (POM) and ethylene vinyl acetate (EVA) indicate various exposure sources, including food packaging and cosmetics. For example, PET and PP are widely used in textiles and drink containers, while polyvinyl chloride (PVC) is typically sourced from pipes and medical equipment [48, 49].
Microplastics (MPs) have been detected in over 15 human biological matrices, indicating their widespread presence and potential health implications. These include blood, placenta, liver, lungs, spleen, breast milk, and faeces [50, 51]. The pyrolysis–gas chromatography-mass spectrometry (Py-GC–MS), of human blood samples revealed an average MP-concentration of 1.6 µg/mL, with PET, PE, and PS as predominant polymers [19]. Also, in other studies, an alarming detection of 3 MPs/g was reported in the placenta and meconium, critical indicators of prenatal exposure [17, 18]. A recent study also revealed that in 39 individuals of 45 pregnant women subjects, a diverse collection of MPs was detected in the amniotic fluid [52]. Moreover, another recent study revealed the presence of MPs in human respiratory samples, including pleural fluid, sputum and bronchoalveolar lavage fluid [46].
Recently, there has been alarming evidence that indicates that prolonged exposure to MPs can cause human carcinogenesis [53]. Two recent reviews have examined the carcinogenic potential of MPs and have both concluded that there is probably a connection [54, 55]. But as Domenech and colleagues note, most of the research has involved short-term rodent studies or in vitro models, making it impossible to draw firm conclusions. Carcinogenesis may be broadly classified as genotoxic and non-genotoxic [14]. Genotoxic carcinogenesis is the direct result of mutagen-induced DNA damage. MPs belong to the category of hazardous chemicals that are surface-associated and acquired through environmental means, such as hydrophobic organic compounds (HOCs), polycyclic aromatic hydrocarbons (PAHs), and persistent organic pollutants (POPs) [14, 56].
Errors during cell division may result in non-genotoxic carcinogenesis. Within this context, MPs have the potential to induce inflammation and/or transfer estrogenic compounds that interact with cell surface estrogen receptors, increasing cell division and initiating non-genotoxic carcinogenesis [14]. Microplastics allow heavy metals like cadmium, PFAS, flame retardants, and bisphenols, as well as additives like phthalates, to seep out of them. Many are endocrine-disrupting chemicals (EDCs), which may raise the risk of breast cancer by acting, at low concentrations, like estrogen [14]. Exposure to microplastics damages the alveolar structure, impairs the function of the airway barrier, and interferes with the biophysical function of pulmonary surfactants. Lung epithelial cells exposed to microplastics undergo both apoptosis and inhibition of proliferation, which eventually results in lung cancer [57]. Humans ingest microplastics at an increasing age and in greater quantities. As MPs move through the digestive system, they come into contact with the body’s regular physiological processes, especially in the colon and rectum, where they may interact with the mucus layer that protects the colon from damage and result in colon cancer [14].
Heavy metal pollution has garnered international attention in recent decades. Despite being seen as new pollutants of worldwide concern in recent years, plastic polymers have been utilized for many years; therefore, MPs/NMPs and heavy metals have most likely always coexisted in large quantities in the environment. Though their interaction mechanisms and combined impacts are not well known, MPs pollution and their interaction with heavy metal ions have recently drawn international attention [58]. Interaction between MPs and heavy metal was first reported by Ashton et al. in 2010 and after that a few enrichments of interplay between types of MPs and heavy metals such as Ni, Co, Zn, Pb, Cr, Ag and Hg [59–63]. At the same time, it is noted that the uptake of heavy metals on unmodified original MPs is nearly insignificant, while beached/eroded/weathered MPs, as well as those altered by the addition of organic matter, are capable of accumulating heavy metals. The direct engagement between MPs and heavy metals primarily pertains to the interaction between MPs and heavy metals in conditions of free contact, typically taking place in a liquid environment. The mechanism of direct interaction primarily encompasses three (1) Electrostatic attraction along with surface A primary mechanism for the adsorption of heavy metal ions. Heavy metals engage with polar (or charged MPs via coulombic interaction [64, 65]; (2) MPs create new complexes through sorption and/or bioaccumulation by biofilms and natural organic matter, leading to altered surface area [66–69]; (3) MPs’ interactions include precipitation/coprecipitation with heavy metal ions or their complexes, co-precipitate alongside hydrous oxides of Fe and Mn. Nonetheless, there are few studies available [70]. In all biological systems, exposure to MPs can lead to particle toxicity, oxidative stress, and inflammation when concentrations are high or individual susceptibility is elevated; furthermore, their persistent nature hinders removal from the organism, resulting in chronic inflammation and an increased risk of neoplasia and cancer [71]. It has been determined that the harmfulness of MPs is mainly affected by exposure levels, particle composition, trapped pollutants, organs affected, and personal vulnerability; therefore, the essential dose that enters the systemic circulation, as well as bioavailability and bioaccessibility, produces negative effects. The interplay between the two kinds of pollutants can activate synergistic, antagonistic, or potentiating influences on organisms. Due to the challenges in assessing the real risks of coexposure to MPs and heavy metals in humans, their impacts remain unclear [72–74]. MPs can move through the food chain, increasing the toxicity of heavy metals, which negatively affects organisms and ultimately results in cytotoxicity, genetic mutations, cancers, and even the transfer of mutated genes to the next generation. Thus, co-exposure of heavy metals and MPs could affect communities and further affect the whole ecosystem.
Environmental aging and weathering significantly transform the physicochemical properties of MPs, often enhancing their bioactivity and ecological toxicity. Aging processes including ultraviolet (UV) irradiation, thermal oxidation, mechanical abrasion, and microbial colonization—introduce oxidized functional groups (e.g., hydroxyl, carbonyl, carboxyl) and increase surface roughness, which in turn elevate hydrophilicity and the capacity to adsorb environmental pollutants [75, 76]. The altered physicochemical properties of aged microplastics (MPs) significantly influence their bioactivity and ecological interactions, with critical implications for environmental and organismal health. Aged MPs can act as carriers for pollutants, including heavy metals, persistent organic pollutants (POPs), and engineered nanoparticles, enhancing contaminant bioavailability and transport in ecosystems [76]. Their modified surface properties also affect microbial colonization, promoting the formation of diverse plastisphere communities that may include plastic-degrading microbes or pathogens, with potential consequences for nutrient cycling in aquatic systems [77].
Recent studies have demonstrated that aged microplastics exhibit considerable alterations in their morphology and surface characteristics, such as specific surface area, hydrophobicity, and functional groups, which can affect their capacity to adsorb organic contaminants. However, the mechanisms through which the aging of microplastics influences the sorption of these contaminants remain poorly elucidated, particularly regarding their bioavailability in environmental systems [78]. The aging process of microplastics was simulated by employing a combination of UV irradiation and persulfate oxidation methods. This aging resulted in notable modifications to the surface properties of microplastics, including a reduction in hydrophobicity and an increase in specific surface area and oxygenated functional groups. The changes are primarily attributed to electrostatic interactions between the microplastics and the products of aging. Consequently, aging significantly enhanced the adsorption capacity of microplastics, with hydrogen bonding and π-π interactions identified as the principal mechanisms driving this adsorption. Future research should prioritize the long-term effects of microplastic aging on bioaccumulation and the ecotoxicological consequences of organic contaminants [79]. Microplastics exposed to UV irradiation on soil surfaces showed the most pronounced changes in particle size, surface morphology, functional groups, and thermal stability, indicating that photo-oxidative degradation plays a critical role in the weathering of microplastics. Challenges in microplastic weathering studies arise from the density differences between microplastics and soil, along with the high static charges created during abrasion. Ultraviolet radiation is known to initiate free radical attacks in polymer matrices, leading to chain scission followed by hydrolysis and oxidation. The environmental conditions and weathering processes can significantly modify the toxicity profiles of microplastics. Hence, it is essential that ecotoxicological evaluations utilize aged microplastics to accurately assess their impact on organisms. While microplastics are prevalent in the human body and experience aging through prolonged exposure to both indoor and outdoor conditions, Lee et al. (2025) suggested that prolonged environmental exposure to microplastics may have significant detrimental effects on cancer patients by influencing both cancer cells and immune responses. Although recent research has highlighted the role of microplastics in cancer growth and metastasis in animal models, the specific properties of microplastics that contribute to these effects are still poorly understood [80, 81].
The physicochemical characteristics of micro- and nanoplastics, particularly particle size, surface charge, and polymer composition, profoundly influence their biological interactions, including cellular uptake, biodistribution, and cytotoxicity. Smaller particles, particularly in the nanoscale range (< 100 nm), exhibit enhanced cellular internalization due to their greater surface area and capacity to traverse biological barriers, as demonstrated in multiple in vitro studies employing epithelial and immune cell models [82, 83]. Surface charge further modulates uptake dynamics; positively charged (amine-modified) polystyrene nanoplastics (PS-NPs) exhibit markedly higher cellular adhesion and internalization compared to neutral or negatively charged counterparts, often resulting in elevated oxidative stress and apoptosis [15, 84]. The toxicity of MPs/ NPs is closely linked to their polymer composition, with different materials exhibiting distinct biointeractions and pathological effects. Hydrophobic polymers like polyethylene (PE) and polystyrene (PS) readily interact with cell membranes, enhancing cellular uptake and inducing oxidative stress and inflammatory responses, particularly in the gastrointestinal tract and lungs [85, 86]. Smaller nanoplastics (< 100 nm), such as PS, can cross biological barriers, entering systemic circulation and potentially reaching sensitive organs [87]. Polyvinyl chloride (PVC), commonly released as respirable particles from industrial sources, is associated with lung inflammation and oxidative damage, while polyurethane (PU) fibres, which are frequently detected in lung tissue and sputum, have demonstrated significant respiratory toxicity [87]. Polyethylene terephthalate (PET) and polypropylene (PP) are prevalent in human samples, including placenta and breast milk, raising concerns about developmental and long-term health impacts. Surface modifications (e.g., oxidation) further influence bioavailability and toxicity by altering particle-cell interactions. Collectively, these findings underscore the need for polymer-specific toxicological assessments to better understand the carcinogenic and systemic risks posed by MPs in humans.
Recently, there has been alarming evidence that indicates that prolonged exposure to MPs can cause human carcinogenesis [88]. Two recent reviews [89, 90] have examined the carcinogenic potential of MPs and have both concluded that there is probably a connection [91, 92]. But as Domenech and colleagues note, most of the research has involved short-term rodent studies or in vitro models, making it impossible to draw firm conclusions. Carcinogenesis may be broadly classified as genotoxic and non-genotoxic [93]. Genotoxic carcinogenesis is the direct result of mutagen-induced DNA damage. MPs belong to the category of hazardous chemicals that are surface-associated and acquired through environmental means, such as hydrophobic organic compounds (HOCs), polycyclic aromatic hydrocarbons (PAHs), and persistent organic pollutants (POPs) [94, 95].
Errors during cell division may result in non-genotoxic carcinogenesis. Within this context, MPs have the potential to induce inflammation and/or transfer estrogenic compounds that interact with cell surface estrogen receptors, increasing cell division and initiating non-genotoxic carcinogenesis [14]. Microplastics allow heavy metals like cadmium, PFAS, flame retardants, and bisphenols, as well as additives like phthalates, to seep out of them. Many are endocrine-disrupting chemicals (EDCs), which may raise the risk of breast cancer by acting, at low concentrations, like estrogen [14]. Exposure to microplastics damages the alveolar structure, impairs the function of the airway barrier, and interferes with the biophysical function of pulmonary surfactants. Lung epithelial cells exposed to microplastics undergo both apoptosis and inhibition of proliferation, which eventually results in lung cancer [96]. Humans ingest microplastics at an increasing age and in greater quantities. As MPs move through the digestive system, they come into contact with the body’s regular physiological processes, especially in the colon and rectum, where they may interact with the mucus layer that protects the colon from damage and result in colon cancer [14].
In 2020, the global cancer burden manifested with 9,958,133 deaths and 19,292,789 newly reported cases across all ages and genders, as per Globocan 2020 [97]. Breast cancer is placed in the highest ranking in occurrence with 2,261,419 cases (11.7%), while lung cancer is closely followed with 2,206,771 cases (11.4%). Mortality reflected a different pattern, with lung cancer leading to 1,796,144 deaths (18%), surpassing breast cancer-induced mortality. Colorectal, prostate, and stomach cancers also contributed significantly to the morbidity and mortality landscape. Notably, cervical uterine cancer reported 604,127 cases (3.1%), while pancreatic cancer accounted for 466,003 deaths (4.7%). These findings underscore the urgent need for targeted prevention and intervention strategies.
Although there is a considerable amount of literature available on the toxicological implications of micro- or nanoparticles, only a few reports are available highlighting the role of microplastics in cancer or the underlying mechanism. In this review, we have discussed in detail the etiological roles of MPs/NPs in different cancers and also the different oncogenic signalling activated in in vitro and in vivo experimental models due to the MP exposure.
The published documents were retrieved electronic databases including PubMed, Scopus, Web of Science, Science Direct databases etc. We included the studies published from 2008 to 2025. The keywords query terms were ‘Microplastics and cancer’, ‘Polyamide microplastics for cancer’, ‘Polyethylene microplastics cancer’, ‘Polyethylene terephthalate microplastics for cancer’, ‘Polylactic acid microplastics for cancer’, ‘Polymethyl methacrylate microplastics for cancer’, ‘Polypropylene microplastics cancer’, ‘Polystyrene microplastics cancer’, ‘Polyurethane microplastics for cancer’, ‘Polyvinyl Chloride microplastics cancer’, for retrieving the data from the PubMed database. Papers highlighting microplastics/nanoplastics (MP/NP)- induced toxicity were not considered in this review. The data structures were depicted as bar diagrammatic representations in Fig. 1. The selection of studies adhered to the PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to ensure methodological rigor, transparency, and reproducibility of the review process [98, 99]. Studies were included based on the following (i) original research articles investigating the association between microplastic (MP) or nanoplastic (NP) exposure and cancer-related outcomes; (ii) studies employing in vitro, in vivo, or human systems; (iii) availability of quantifiable biological or molecular endpoints pertinent to carcinogenesis, such as oxidative stress, inflammation, genotoxicity, or tumor formation; and (iv) publications in English with full-text availability.
Exclusion criteria (i) studies unrelated to MPs/NPs or cancer; (ii) conference abstracts, editorials, perspectives, or commentaries lacking original data; (iii) duplicate records; (iv) articles lacking methodological clarity or outcome specificity; (v) studies that did not report cancer-relevant endpoints; and (vi) insufficient information on the physicochemical characteristics of pollutants.
All references were imported into EndNote (version 21.5) for deduplication and a blinded screening of titles and abstracts were performed using the Rayyan QCRI platform.
All eligible studies underwent detailed screening, and relevant data were systematically extracted using a standardized Microsoft Excel template to ensure consistency and comparability. The extracted parameters author(s), year of publication, experimental design (in vitro, in vivo, ex vivo), model system employed (human, animal, or cell-based), microplastic or nanoplastic type, polymer composition, particle size, exposure concentration, duration and route of exposure, target cell or tissue, and reported cancer-related endpoints (e.g., reactive oxygen species [ROS] generation, DNA damage, inflammatory markers, cellular proliferation, or tumorigenesis). To facilitate meaningful interpretation, the biological responses observed in each study were categorized into five distinct toxicity non-toxic, slightly toxic, toxic, size-dependent toxic, and concentration-dependent toxic. This classification allowed for comparative insights into how physicochemical properties and exposure parameters modulate the oncogenic potential of MPs/NPs across diverse biological systems.
A total of 4,705 articles were rigorous screening and filtering; literature search yielded through different databases and additional searches. Subsequently removing 1,268 duplicates, 3,437 records were screened based on title and abstract. Among them, 2,982 were excused because of partial coverage, lack of relevant to cancer or microplastics, or inadequate data on pollutants. The remaining 455 full-text articles were evaluated for suitability. Subsequently, 172 articles were excluded for being reviewed, contained no cancer-related information, and/or did not address micro/nanoplastics or were filtered out because of language/accessibility reasons. A final set of 283 articles were deemed potentially relevant, out of which 223 studies met the full inclusion criteria and were included in this review, as shown in Fig. 3. All these studies analyzed the oncogenicity of microp/nanoplastics using different models with the following mechanisms that were highlighted, including oxidative stress, DNA damage, persistent inflammation, and an altered signaling pathway. The evidence shows the increasing interest in the carcinogenic consciousness of micro/nanoplastics and refers to the necessity to concentrate further research in the direction of this upcoming field of environmental oncology.
Fig. 3PRISMA Flow Diagram of Study Selection Process
The multistage process of carcinogenesis is comprised of three successive progression, promotion, and initiation. A typical cell experiences an irreversible genetic alteration that allows for independent development at the initiation step. Then, during the promotion step, the started cell experiences aberrant clonal growth. The last step, known as progression, involves the neoplastic lesion changing to a fully invasive malignant tumor [100]. Carcinogens can function as initiators or promotors, depending on their ability to cause mutations in an ordinary cell. Initiators can also work as enhancers of the carcinogenic process without necessarily causing mutagenic activity [101]. As a result, carcinogens are divided into two those that are genotoxic and those that are not [102].
Chemicals and agents have two potential mechanisms of primary, where the molecule acts on the target cell, and secondary when the target cell has an inflammatory response resulting in secondary consequences. The main mechanism may be a direct contact between the material and DNA or it may be an indirect impact that is transmitted through other molecules (such as; inhibition of DNA repair mechanisms, production of reactive oxygen species, etc.) [52, 103]. However, there are a variety of mechanisms including immunological suppression, receptor-mediated endocrine regulation, mitogenicsignalling, and epigenetic modifications that underlie non-genotoxic carcinogenicity, some of which are currently unknown [92, 102, 104].
In cancer, various cellular processes and signalling pathways play crucial roles in tumorigenesis and disease progression (Fig. 4**).** The cell cycle, regulated by numerous checkpoints and control mechanisms, can become dysregulated, leading to uncontrolled cell proliferation, a hallmark of cancer [105]. Hippo signalling, involved in cell growth, differentiation, and organ size control, is frequently altered in cancer, impacting tissue homeostasis and tumour development [106].
Fig. 4Dysregulated Oncogenic Signalling Pathways in Cancer Initiation and Progression. This figure illustrates the intricate network of oncogenic signalling pathways contributing to cancer initiation, progression, and metastasis. The PI3K/AKT/mTOR pathway is shown to regulate cell survival, proliferation, and metabolism through intermediates such as PDK1, mTOR, AKT, GSK-3β, FOXO, and S6K1. The DNA damage response pathway, involving ATM, ATR, and MDM2, plays a crucial role in genomic stability and tumor suppression. The JAK-STAT pathway, activated by cytokine receptors, promotes inflammation-driven tumorigenesis through JAK and STAT phosphorylation cascades. The RAS-RAF-MEK-ERK signalling axis, frequently dysregulated in cancer, is shown driving cell proliferation and differentiation through sequential phosphorylation events. Meanwhile, the Notch signalling pathway is depicted, highlighting the activation of Notch receptors by JAGGED I/II ligands, followed by ADAM and γ-secretase cleavage to release the Notch Intracellular Domain (NICD), which translocates to the nucleus to regulate target genes. Exposure to microplastics (MPs) and nanoparticles (NPs) is linked to uncontrolled cellular proliferation, inflammatory cytokine production (IL-1β, IL-6, IL-8, TNF-α), and cancer stem cell activation (Oct3/4, Notch2, Nanog, Klf4, CD44). The figure also illustrates the potential impact of MPs/NPs on chemotherapeutic drug responses, with implications for cancer treatment resistance
Mycsignalling, a key regulator of cell growth and proliferation, is often overexpressed or deregulated in cancer cells, driving aberrant cell division and survival [94]. Notch signalling, essential for cell fate determination and tissue patterning, is frequently dysregulated in cancer, contributing to tumour growth and metastasis. Oxidative stress response mediated by the NRF2 pathway becomes dysregulated in cancer, affecting cellular redox balance and promoting tumour progression. PI-3-Kinase signalling, involved in cell growth, survival, and metabolism, is frequently hyperactivated in cancer, promoting tumour growth and resistance to therapy.
Receptor tyrosine kinase (RTK) signalling, along with the downstream RAS/MAPK pathway, plays a critical role in regulating cell proliferation, survival, and differentiation, frequently dysregulated in cancer through mutations or overexpression. TGFβ signalling, regulating various cellular processes including cell growth, differentiation, and apoptosis, can exhibit dual roles in cancer depending on the tumour stage and microenvironment [107]. P53, known as the “guardian of the genome,” is a tumour suppressor protein crucial for maintaining genomic stability and inducing apoptosis or cell cycle arrest in response to DNA damage or cellular stress. Dysfunctional P53 signalingis a hallmark of many cancers. β-catenin/WNT signalling, crucial for embryonic development and tissue homeostasis, is often dysregulated in cancer, promoting tumour initiation, progression, and metastasis. These pathways represent intricate networks that contribute to cancer development and progression, offering potential targets for therapeutic intervention [95].
The JAK-STAT pathway plays a significant role in cancer progression by facilitating communication between cell surface receptors and the nucleus, leading to the expression of genes that promote tumour growth and metastasis. This pathway can act as a driver of cancer, influencing various malignancies, including prostate cancer, breast cancer, leukaemia, and cervical cancer, to name a few [96]. The RAS-RAF-MEK-ERK signalingpathway, also known as the MAPK pathway, is crucial for cell proliferation and survival. Aberrant activation of this pathway is implicated in many cancers, with approximately 33% of tumorsharboring RAS mutations that lead to its dysregulation [107]. The MAPKs (mitogen-activated protein kinases) are serine/threonine kinases that play crucial roles in cellular responses to various external and internal stimuli, including mitogens, osmotic stress, heat shock, and proinflammatory cytokines. These kinases are key regulators of several essential cellular processes, such as proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis. In mammals, there are four major MAPK (1) ERK1/2, (2) c-Jun N-terminal kinases (JNK1–3), (3) p38, and (4) ERK5 [95]. MAPK signalling operates through a cascade of phosphorylation events involving three sequentially activated a MAPK kinase kinase(MAPKKK, also known as MAP3K), a MAPK kinase (MAPKK or MEK), and the MAPK itself. These cascades are often triggered by cell-surface receptors through cytoplasmic signalling intermediates and are tightly regulated by phosphorylation events. Dysregulation of MAPK pathways is frequently observed in various human cancers [51].
Among the MAPK families, ERK1 and ERK2 are extensively studied due to their pivotal roles in promoting cell proliferation and survival. Conversely, the JNK and p38 pathways are primarily associated with cellular stress responses and the regulation of apoptosis. Notably, the RAS/RAF/MEK/ERK signalingaxis is the most extensively investigated pathway, as it plays a central role in controlling cell proliferation and differentiation, positioning it as a critical component of the cellular signal transduction network [15].
Another extensively studied, highly deregulated signalling cascade is the Notch signalling pathway, which plays a pivotal role in the pathogenesis of numerous human cancers, including lung, cervical, colon, pancreatic, and renal carcinomas, among others [108].
Notably, elevated expression levels of Notch-1 and its ligand Jagged-1 have been strongly correlated with adverse clinical outcomes, including poor prognosis, reduced survival rates, and the development of chemoresistance in these cancers. The activation of Notch signalingis initiated by the interaction between Notch receptors and their ligands, such as Jagged-1 or Jagged-2, followed by a cascade of proteolytic events. Notch receptors are transmembrane proteins composed of three distinct an extracellular domain, a transmembrane domain, and a cytoplasmic domain. The first cleavage event, termed S1, occurs within the Golgi apparatus and is mediated by a furin-like convertase. This cleavage generates a heterodimeric receptor that is subsequently transported to the cell surface. Upon ligand binding, the receptor undergoes a second cleavage, S2, catalysed by ADAM (a disintegrin and metalloproteinase) family proteases or TACE (tumour necrosis factor-α–converting enzyme) [109].
This cleavage occurs at an extracellular site between the Ala (1710) and Val (1711) residues, resulting in the release of the Notch extracellular domain. The remaining transmembrane fragment is then subjected to a third cleavage, S3, mediated by the γ-secretase complex. This intramembrane proteolysis releases the Notch intracellular domain (NICD), which translocates to the nucleus to regulate gene expression of downstream target genes, including Hes-1, Hey-1, Akt, and PTEN, which are integral to cell proliferation, survival, and differentiation [110]. The Fig. 4 summarises the intricate network of oncogenic signalling pathways that are highly dysregulated in cancer and play a pivotal role in cancer initiation, progression, and metastasis.
Microplastic and nanoplastic particles can enter cells through several pathways, depending largely on particle size and cell type [15]. Key uptake mechanisms
Specialized immune cells (e.g. macrophages, neutrophils, dendritic cells) can engulf larger microplastics (generally > 0.5 μm) via phagocytic receptors [111]. This active process internalizes big particles into phagosomes, which often fuse with lysosomes for attempted degradation.
Smaller particles (< 0.5 μm) are readily internalized by non-phagocytic cells via endocytic pathways [15, 111]. This encompasses clathrin-mediated endocytosis and caveolin-mediated endocytosis (sometimes termed micropinocytosis), which form 100–150 nm vesicles that take up nanoplastics along with extracellular fluid. Such receptor-mediated endocytosis is a common route for nanoplastics in epithelial and other somatic cells.
Cells can also engulf fluid and particles non-selectively through actin-driven ruffles (macropinosomes). This pathway can internalize sub-micron plastics in bulk. (Notably, in one intestinal cell model, macropinocytosis was considered but largely ruled out in favor of other routes [112]. However, many cancer cells exhibit micropinocytosis [113], so it may contribute to MP uptake in tumors.
Nanoplastics at the tens-of-nanometers scale can sometimes penetrate cell membranes directly. For example, ~ 20 nm particles have been observed crossing lipid bilayers via passive permeation [111]. Such diffusion (driven by van der Waals and electrostatic forces) is only efficient for very small (< 50 nm) particles [111].
Once inside, these particles tend to accumulate rather than being expelled. Studies show that micro/nanoplastics are sequestered in endosomal-lysosomal compartments and are not readily eliminated from cells [82]. For instance, fluorescent polystyrene beads under 1 μm have been found co-localized in lysosomes of human gastrointestinal cancer cells. During cell division, internalized particles partition into daughter cells, meaning the plastic burden can persist and even propagate as cells proliferate [82]. Importantly, particle size influences the extent of uptake and subsequent smaller nanoplastics (e.g. 0.25 μm) are taken up more efficiently and have been shown to significantly increase cancer cell migratory ability, potentially promoting metastasis [114]. In summary, MPs/NPs employ both active endocytic (phagocytic and pinocytic) pathways and passive diffusion to infiltrate cells, leading to their accumulation in cellular compartments.
Laboratory studies with cultured cancer cells and 3D tumor spheroids allow high-resolution tracking of microplastic localization at the cellular level. For example, the human colorectal cancer cell lines (e.g. HCT116, HT29) have v internalized polystyrene particles inside cells up to 1 μm and even 10 μm, but 0.1–0.5 μm nanoplastics are absorbed most efficiently [82]. Once internalized, these particles reside predominantly in endosomes/lysosomes vesicular compartment in the cytoplasm and activate certain cellular functions [15]. Interestingly in 3D multicellular tumor spheroids (which mimic avascular tumor nodules), microplastics showed a non-uniform spatial distribution, they tended to accumulate in the spheroid core, which is the nutrient-deprived, non-proliferating region. Cells at the periphery (actively proliferating) internalized particles and, as they divided, passed some on to their progeny, but a significant fraction of particles ended up retained in the central cells that had ceased dividing. This resulted in a higher concentration of MPs in the spheroid interior [82]. One hypothesis is that limited diffusion and lack of cell division-mediated dilution in the core cause particles to get “trapped” there. Notably, the presence of 0.25 μm nanoplastics induced migratory and invasive behavior in these cancer cells, consistent with EMT-like changes that could facilitate metastasis. This suggests that beyond simply localizing in cells, micro/nanoplastics might actively perturb cellular functions (through oxidative stress or signaling pathway interference). In co-culture experiments, immune cells (like macrophages) can readily phagocytose microplastics and in turn interact with cancer cells, potentially transferring some particles or releasing inflammatory signals. For example, human macrophages exposed to MPs adopt a pro-inflammatory, metabolically active state, which in a tumor context could influence tumor-associated macrophage (TAM) behavior and thus tumor inflammation [115]. In summary, in vitro models demonstrate that MPs/NPs can penetrate cancer cells and organoids, localize primarily in vesicular compartments (especially lysosomes), and concentrate in certain cellular sub-populations (quiescent or migratory cells).
Emerging evidence indicates that microplastics can disseminate throughout the human body and even preferentially accumulate in certain diseased tissues. Researchers have detected microscopic plastics in numerous human organs – from the lungs and liver to the placenta and even the bloodstream [15, 56, 57]. Notably, recent studies have focused on cancerous tissues, revealing measurable microplastic burdens in human tumors [116–122]. Deng et al. (2024) provided the first quantitative analysis of microplastics in human cancer tissue by comparing prostate tumor and adjacent normal (para-tumor) tissues [122]. Using scanning electron microscopy (SEM) and laser direct infrared (LDIR) imaging spectroscopy, they identified at least four polymer types – polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), and polystyrene (PS) – embedded in prostate tissues. Strikingly, tumor samples contained a higher load of microplastics (~ 290 µg per gram of tissue) than the surrounding non-tumorous prostate (~ 181 µg/g). The particles ranged from 20 to 100 μm in size, with tumor tissues tending to harbor larger fragments (50–100 μm) whereas the normal tissue fragments were mostly 20–30 μm. This suggests not only a greater abundance but also a retention of bigger microplastics in the tumor microenvironment. Although causality is unproven, the prostate study demonstrates that MPs do localize in human tumor tissues and at higher concentrations than in surrounding tissue. One hypothesis is that the leaky vasculature and poor lymphatic drainage of tumors (the enhanced permeability and retention effect) allow more MPs to extravasate and remain in tumors compared to healthy tissue. Additionally, tumour-associated inflammation may “trap” particles, analogous to findings that atherosclerotic lesions accumulate more microplastics than normal vessel walls [123]. Similarly, Wang et al. analyzed human penile cancer tissues and adjacent normal tissues, finding microplastics in 85% of tumor samples [121]. The cancerous tissue had a significantly higher particle count and greater polymer diversity than normal tissue from the same patients. On average ~ 6.4 microplastic particles per gramtissue, were present in the tumors, indicating that malignant tissue can serve as a sink for the MPs. The similar size distributions in tumour vs. normal (unlike the prostate case) suggest that all particle size classes were elevated in the tumours. All these observations potentially reflect a general increase in exposure or uptake in the tumor microenvironment rather than selective retention of larger particles. This study confirms qualitatively and quantitatively that human cancers (even in internal, well-vascularized tissues like penile corpora) can harbourmicroplastics at higher concentrations than adjacent healthy tissue [121].
These findings illustrate that inhaled or ingested microplastics can translocate across organ barriers (gut, air-blood barrier, placental barrier, blood-brain barrier) and lodge in distant tissues. Inflammatory or fibrotic lesions might preferentially accumulate MPs, for example, the concentration of microplastics in diseased cardiac tissues and atherosclerotic plaques is higher than in normal heart and artery tissue [124]. Extrapolating to cancer, the chronic inflammation and abnormal vasculature of tumors likely facilitate microplastic deposition in the tumor stroma. Indeed, both prostate and penile cancer studies support that cancerous lesions contain more microplastics than surrounding tissue, echoing a pattern that injured or abnormal tissues tend to sequester these particles. Some reports have even linked elevated microplastic exposure to higher incidence of certain conditions like inflammatory bowel disease, fibrotic lesions, and possibly cancers [123].
Rodent studies have shown that ingested or inhaled microplastics distribute systemically, with highest accumulation often in filtering and immune organs. For example, mice fed fluorescent polystyrene MPs accumulated particles in the gut, liver, and kidneys, with distribution patterns depending on particle size (smaller 5 μm vs. larger 20 μm showing different organ tropism) [125]. Over time, these particles persisted in tissues and elicited oxidative stress and metabolic disturbances. Crucially, some animal experiments have directly examined microplastics in the context of the tumour-microenvironment. For example, Chen et al. demonstrated that in mice, exposure to nanoplastics accelerated the growth of implanted ovarian cancer tumours [126] and the polystyrene nanoplastics appeared to stimulate a pro-tumour environment, leading to faster tumour progression [126]. Several studies also revealed that zebrafish exposed to aqueous environments containing MPs/NPs had significant changes in the expression of certain genes associated with tumorigenesis [127, 128]. Moreover, Accumulation of microplastics in critical organs like bone marrow, the primary site of hematopoiesis, poses significant risks. Microplastics entering the bone marrowmay disrupt normal hematopoietic processes, potentially leading to aberrant proliferation and differentiation of blood cells (red blood cells, white blood cells, platelets) and elevating the risk of hematological malignancies such as leukemia and lymphoma [129]. Given that bone marrow is a well-vascularized niche with sinusoidal blood flow, it underscores how small plastic particles in circulation can lodge in niche microenvironments.
Tumors are complex ecosystems composed of malignant parenchymal cells and a dynamic stroma that includes immune cells, fibroblasts, blood vessels, and extracellular matrix (ECM) components [130, 131]. A. Interaction with TME components.
MPs are efficiently phagocytosed by macrophages, which can undergo immunometabolic reprogramming upon exposure, marked by increased glycolysis, surface co-stimulatory molecule expression, and cytokine release [115]. MPs once inside tumour tissue are not evenly distributed but appear to accumulate in stromal compartments preferentially [132]. This is partially due to the active phagocytic behaviour of immune cells, such as tumour-associated macrophages (TAMs), which internalize MPs and become metabolically reprogrammed [115]. Yang et al. demonstrated that polyethene-NPs and polystyrene-NPs promoted colorectal tumor growth by activating IL-1β in colonic macrophages, driving regulatory T-cell differentiation and T-cell exhaustion [132]. Merkley et al. further showed that MP phagocytosis by macrophages triggered a glycolytic shift and cytokine production, supporting an immunologically active but dysfunctional TME [115]. Wolff et al. observed M1 polarization of dendritic cells and macrophages after MP exposure, potentially contributing to a pro-inflammatory TME [133].
Fibroblasts internalize MPs, triggering ROS generation, ER stress, and upregulation of profibrotic genes like PAI-1 and collagen I [134]. MPs also induce fibroblast-to-myofibroblast transition (α-SMA, pro-collagen Iα), altering ECM dynamics [135].
MPs disturb ECM homeostasis by upregulating MMP-1 and downregulating structural and adhesive molecules (e.g., elastin, laminins, integrins), compromising tissue integrity [136, 137].
MPs promote endothelial inflammation and dysfunction, marked by adhesion molecule upregulation and cytokine secretion [138]. These changes can initiate tumor angiogenesis and coagulopathy via pathways like JAK1/STAT3 [139].
Collectively, MPs disrupt multiple TME components, shaping a niche that may favor cancer progression.
MPs are predominantly found in lysosomes and endosomes within cells. Larger particles do not enter nuclei but can cause lysosomal swelling or rupture. Extracellularly, MPs may embed in the ECM, where irregular shapes can cause mechanical damage, inflammation, or fibrosis [140].
(a) Epithelial Linings: MPs frequently accumulate near epithelial surfaces. In colon or lung cancers, MPs can settle at tumor–lumen interfaces, especially where the mucus barrier is compromised [14]. Donkers et al. confirmed trans-epithelial movement of MPs in human organoid models [141].
(b) Direct Luminal Exposure:Tumors protruding into the gut or airway lumen are continually exposed to ingested or inhaled MPs. Pan et al. identified microplastics on the luminal side of colorectal tumors and observed higher MP concentrations within tumor cores, facilitated by elevated clathrin-mediated endocytosis [20, 142].
(c) Stem Cell Niches:Tumor and physiological stem cell niches, like the intestinal crypt or perivascular regions, are vulnerable to MP deposition. MPs have been detected in bone marrow [129], and Rafazi et al. showed that polyethene and polypropylene MPs accumulate around, though not within, cancer stem-like spheroids in AGS-derived 3D spheroid models [143].
Thus, the spatial distribution of microplastics in tumours is not random. MPs tend to localize at epithelial interfaces, in the stromal and immune compartments, and near stem cell niches, regions with high biological activity or compromised barriers. These interactions can alter the tumor microenvironment, potentially influencing tumor progression and therapy response.
Emerging evidence has demonstrated the presence and differential accumulation of microplastics (MPs) in various human tumor tissues, highlighting a potential environmental factor contributing to cancer development and progression. A recent landmark study by Zhao et al. (2024) provided the first comprehensive quantification and characterization of MPs in multiple human cancer tissues using pyrolysis-gas chromatography-mass spectrometry (Py-GCMS) [116]. The study analyzedtumor samples from 61 patients diagnosed with lung, gastric, colorectal, cervical, pancreatic, and esophageal cancers, revealing distinct patterns of MPs accumulation across cancer types. Some additional recent studies, most of which were published in 2025, also revealed the abundance of MPs in various cancers, such as breast, penile, colitis-associated cancer (CAC), etc., to name a few. Examples of cancer tissues from patient samples that have been found positive for MP-accumulation are summarized as
As reported by Zhao et al., lung cancer tissues showed the highest detection rate of MPs, with 80% of the analyzed samples being positive for MPs [116]. Polystyrene microplastics(PS-MPs) was the most predominant polymer detected, with concentrations ranging from 7.89 to 72.31 ng/g of tissue. The higher abundance of MPs in lung tissues is likely attributed to the respiratory tract being a primary route for MP inhalation exposure. According to Kelly et al., microparticles are commonly classified into four categories based on their particles larger than 10 μm, those smaller than 10 μm, particles smaller than 2.5 μm, and ultrafine particles less than 0.1 μm. When inhaled, particles greater than 10 μm generally deposit in the upper airways due to their size. In contrast, particles smaller than 10 μm can reach the bronchioles, while those under 2.5 μm, including ultrafine particles, are capable of penetrating deep into the lungs, reaching the alveolar regions [144]. In the study of Vattanasit et al., particles measuring 5–30 mm can enter through the nose and mouth, settling in the upper respiratory tract. Particulate matter (PM) between 1 and 5 μm tends to deposit in the smaller airways, whereas ultrafine MPs (< 0.1 μm) may penetrate deeper into the lungs, potentially crossing the respiratory barrier into the bloodstream and accumulating in lung tissue [145].
Pancreatic cancer tissues demonstrated a 70% detection rate for MPs, with PS being the dominant polymer, showing the highest tissue concentration among all cancer types (up to 356 ng/g) [116]. Importantly, the study provided evidence of MPs disrupting the tumor immune microenvironment (TIME) in pancreatic cancer, marked by reduced infiltration of cytotoxic immune cells such as CD8 + T cells, NK cells, and dendritic cells, and increased neutrophil presence, suggesting a pro-tumorigenic immunosuppressive environment.
Colorectal cancer tissues exhibited a 50% detection rate of MPs, predominantly comprising PS and polyethylene (PE), with concentrations varying from 10.22 to 41.57 ng/g tissue. These findings are significant given that dietary intake is considered a major route of MP exposure, and the colon is directly exposed to ingested MPs [116]. Interestingly, another seminal study by Pan et al. (2025) investigated the role of microplastics (MPs) in colorectal cancer (CRC) progression and oxaliplatin resistance, employing clinical samples, in vitro assays, and in vivo models [142]. Using laser direct infrared (LDIR) imaging and scanning electron microscopy (SEM), MPs were detected for the first time in human CRC tissues, with polymer types including polyethylene (PE), polystyrene (PS), and polyvinyl chloride (PVC), which indicated a positive correlation between the quantity of MPs and tumor malignancy, particularly with advancing Dukes’ stages of CRC, suggesting a potential role of MPs in tumor progression. The study also revealed that MP-exposure induces protective autophagy in CRC cells through the activation of the mTOR/ULK1 signaling axis. The in vivo experiments using xenograft and azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC mouse models corroborated the in vitro findings. Oral administration of MPs promoted tumor growth, enhanced autophagy markers in tumor tissues, and diminished the antitumor efficacy of oxaliplatin. Moreover, MP-treatment resulted in intestinal inflammation, disruption of the gut barrier, and significant alterations in gut microbiota composition, characterized by an increase in harmful bacteria such as Clostridiales sp. and Lachnoclostridiumsp [142]. These findings highlight MPs as emerging risk factors for CRC aggressiveness and chemoresistance. As mentioned by Maciel-Fiuza et al., exposure to MNPL in the intestine can trigger an inflammatory cascade that disrupts mucosal immunity, alters the gut microbiota, and impairs the function of intestinal immune cells. These disturbances may collectively contribute to the development of gastrointestinal disorders, including inflammatory bowel diseases (IBDs) such as Crohn’s disease (CD) and ulcerative colitis (UC), as well as colorectal cancer (CRC) [146].
As reported by Zhao et al., gastric cancer tissues showed a 40% MP detection rate, with PS and polyvinyl chloride (PVC) being the primary polymers identified [116]. Concentrations ranged between 8.93 and 37.61 ng/g tissue. The presence of MPs in gastric tissues underscores the potential for ingestion-related MP accumulation within the gastrointestinal tract. The lumen of the gastrointestinal (GI) tract poses a significant challenge in studying the absorption rates of nanoplastics. Upon ingestion, nanoparticles undergo various transformations, which can affect their ability to be absorbed and the rate at which this occurs. Within the GI tract, nanoparticles may interact with several molecules, including proteins, lipids, carbohydrates, nucleic acids, ions, and water, all of which can influence their behavior and absorption. The ability of nanoplastics to penetrate the gut epithelium, potentially leading to systemic exposure in humans, is a major concern. Traditionally, research has utilized polystyrene nanoparticles in both in vivo and in vitro studies across various animal models. Walczak et al., estimated oral bioavailability of 50 nm polystyrene nanoparticles is between ten and one hundred times higher than that of microplastics (2–7%). However, much like with microplastics, there is no simple or direct relationship between the size and structure of nanoplastics and their absorption rates [147].
Zhao et al. reported that the cervical cancer tissues demonstrated the lowest detection rate among the positive cases, with 17% of samples containing MPs [116]. PS was the primary polymer detected, although at lower concentrations (6.48–20.77 ng/g tissue) compared to other cancer types. Additionally, two complementary studies in 2024 and 2025, by Xu et al., have revealed significant insights into the accumulation of microplastics (MPs) in cervical cancer tissues, highlighting their potential role in disease progression [118, 119]. Reported by Geyer et al., Polyethylene (PE) and polypropylene (PP) are plastic particles frequently detected in human cervical cancer samples. Notably, these two polymers are also among the most widely produced plastics, with PE being the most commonly manufactured, often used in disposable containers [148]. This widespread use and production likely contribute to their high detection rates in cervical cancer tissues. In a pioneering 2024 study, Xu et al. detected MPs in cervical tumors, adjacent normal tissues, and blood samples using Raman spectroscopy. Thirteen polymer types were identified, with polyethylene (PE, ~ 26%) and polypropylene (PP, ~ 19%) dominating, alongside polyethylene-polypropylene copolymers. MPs were consistently higher in cancerous tissues compared to adjacent normal tissues, and blood samples exhibited the highest abundance and diversity, suggesting systemic circulation [118]. Notably, MPs < 50 μm predominated across all samples, indicating their capacity to penetrate tissues uniformly. Lifestyle factors, particularly frequent consumption of bottled water and plastic-packaged beverages, correlated with elevated MP levels, implicating dietary exposure as a critical source. A follow-up 2025 study by the same group further linked MP accumulation to cervical cancer progression [119]. Analyzingtumors across stages, invasive carcinomas harbored significantly higher MP counts (2.24 ± 1.61 particles/g) than early lesions, with PE and PP remaining predominant. Metabolomic profiling revealed altered carbohydrate metabolism in high-MP tumors, marked by dysregulation of D-mannose and perturbations in amino sugar and nucleotide sugar pathways [116] These metabolic shifts suggest MPs may influence tumor microenvironment dynamics, potentially driving metabolic reprogramming associated with disease advancement. Collectively, these studies establish cervical cancer as a site of MP accumulation, with implications for both disease etiology and progression. The prevalence of PE and PP underscores the role of ubiquitous plastic pollutants, while metabolic findings hint at novel mechanisms by which MPs could modulate cancer biology. Further research is needed to unravel causal relationships and assess long-term health impacts of MP exposure in gynecologic malignancies.
A recent study by Tian et al. (2025) offers essential insights into the formation of microplastics (MPs) in breast cancer (BC) tissues and their mechanistic significance in disease progression [149]. The authors identified substantial accumulation of MPs in BC patient tissues relative to surrounding non-neoplastic tissues by laser direct infrared spectroscopy and scanning electron microscopy. The primary MPs observed were chlorinated polyisoprene and polypropylene particles, with sizes above 100 μm. This discovery highlights the possibility of environmental and nutritional microparticles permeating human cells, especially in cancers. The research also indicated that MPs, particularly 0.5 μm and 60 nm polystyrene particles, infiltrate BC cells (MCF7 and MDA-MB-231) by annexin A2 (ANXA2)-mediated endocytosis. Upon internalization, MPs caused mitochondrial dysfunction, characterized by increased reactive oxygen species (ROS), calcium excess, and reduced mitochondrial membrane potential. The disturbances initiated mitophagy—a selective autophagic mechanism for impaired mitochondria—by upregulating markers including LC3B-II/LC3B-I, PINK1, and Parkin, while concurrently decreasing TOMM20 and P62 levels. Significantly, MPs binding to ANXA2 suppressed IL-17 cytokine exocytosis, hence stimulating the IL-17 signalingpathway. This route, via downstream TRAF6, intensified mitochondrial stress and prolonged mitophagy [149]. Although limitations encompass a limited clinical sample size (3 breast cancer patients) and technological difficulties in identifying sub-20 µmmicroplastics, the study innovatively identifies MPs in human BC tissues and clarifies the ANXA2/IL-17 axis as a new pathway connecting MPs exposure to mitochondrial dysfunction.
The first direct evidence of microplastic (MP) accumulation in human penile cancer (PeC) tissues has been provided by recent pioneering research by Wang et al. (2025), highlighting a potential environmental exposure link in cancer pathogenesis [150]. Laser Direct Infrared (LDIR) spectroscopy was used to evaluate tissue samples from 17 PeC patients to find and characterize MPs in both malignant tissue (CT) and adjacent normal tissue (ANT). The predominant polymer types identified were polyethylene (PE), polypropylene (PP), and polyvinyl chloride (PVC), predominantly within the 20–50 μm size range. The findings showed a far higher abundance and diversity of MPs in the malignant tissue than in the non-cancerous tissue. CT reported an average MP abundance of 7.43 particles/g, compared to ANT’s 5.07 particles/g. This implies that MPs not only penetrate human tissues but could also selectively gather in malignant areas. Interestingly, even if the size distribution of MPs in both CT and ANT was constant, CT showed significantly more diversity and abundance, suggesting a possible involvement of MPs in the tumor microenvironment or carcinogenic progression [150]. In this study, Wang et al. examined the presence and characteristics of microplastics (MPs) in human penile cancer tissues using LDIR spectroscopy to analyze both cancerous and adjacent normal tissue samples. The results revealed a greater abundance and diversity of MPs in the cancerous tissues, with polyethylene (PE), polyamide (PA), and polyvinyl chloride (PVC) being the most commonly detected types, predominantly within the 20–50 μm size range. Importantly, MPs were not only more prevalent in cancerous tissues but also differed in type and distribution compared to the adjacent normal tissues. These findings suggest that MPs may preferentially accumulate in cancerous tissues, raising concerns about their possible involvement in carcinogenesis [121].
Microplastics (MPs) have recently been found and measured in human prostate cancer tissues, suggesting a potential connection between exposure to MPs and the development of prostate cancer. Deng et al. (2024) conducted an important study analysing paired para-tumor and tumor tissues from 22 prostate cancer patients to evaluate the presence, features, and abundance of MPs [122]. With the help of the advanced analytical techniques, including Laser Direct Infrared (LDIR) spectroscopy, Scanning Electron Microscopy (SEM), and Pyrolysis-Gas Chromatography-Mass Spectrometry (Py-GC/MS), various types of microplastics, namely polyamide (PA), polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), polyvinyl chloride (PVC), and polystyrene (PS), were identified in the cancer tissues. Polystyrene (PS) was exclusively identified in tumor tissues, indicating a possible correlation with tumorigenic processes. A positive association was identified between the prevalence of PS in tumor tissues and the frequency of take-out food consumption, underscoring lifestyle-related exposure pathways of MPs. The research indicated that MPs might penetrate the genitourinary system, evading intestinal clearance and accumulating in the prostate, potentially affecting cancer development through mechanisms including oxidative stress, inflammatory signalling, and alteration of androgen receptor pathways. In this study Demirelli E et al., is the first to demonstrate the presence of microplastics in human prostate tissue. The detected microplastics predominantly appeared as pellets, with spherical and fibrous forms observed less frequently. Among the 12 patients analyzed, microplastics were identified in half of the cases, revealing four different types of plastics. Polyamide (Nylon 6) was the most commonly detected, followed by polypropylene, polyacrylic acid, and polydimethylsiloxane [151]. The widespread occurrence of microplastics in various environments and now in multiple organs and systems of the human body is cause for concern. This emerging issue highlights significant knowledge gaps and potential public health risks that warrant further investigation.
These accumulating lines of evidence strongly suggest that Mps may differentially accumulate across diverse cancer types, potentially influencing tumor biology through immunomodulation, metabolic reprogramming, and cell stress responses. Notably, studies have employed a range of detection methodologies, such as pyrolysis-GCMS, Raman spectroscopy, laser direct infrared (LDIR) imaging, and scanning electron microscopy (SEM), to identify and characterize MPs in human tissues. While these techniques provide valuable insights into MP burden, polymer type, and localization, they often face challenges in detecting particles below 20 μm or quantifying trace-level exposures. Given the clinical and environmental significance, there remains an urgent need to develop more sensitive, standardized, and high-throughput MP detection methods tailored for cancer tissues. The selection of cancer types analyzed in this section was based on peer-reviewed clinical studies in which microplastics were detected in patient-derived tumor tissues using the above-mentioned validated techniques. Another major challenge is the limited availability of epidemiologically derived relative risk (RR) or odds ratio (OR) estimates that directly link MP/NP exposure to human cancer outcomes. Hence the cancer types discussed were selected based on published reports that confirmed the detection of micro- or nanoplastics in patient-derived tumor samples. Although direct epidemiological evidence quantifying RR is still emerging, multiple studies have noted higher MP loads in tumor compared to non-tumor tissues, and a positive correlation with disease stage and tumor aggressiveness. These findings suggest a potential dose–response relationship, warranting future long-term cohort studies to determine definitive risk estimates. Such advances will be instrumental in deciphering exposure–effect relationships and establishing MPs as potential oncological risk factors or diagnostic indicators. The detailed summary of the MP/NP-induced cancer incidences is tabulated in Table − 1.
Table 1Accumulation of Microplastics in Different Cancer TypesSL No.Type of CancerTypes of MPs/NPsReferences1Lung CancerPolystyrene (PS)Zhao et al., 2024 [116]2Pancreatic CancerPolystyrene (PS)Zhao et al., 2024 [116]3Colorectal CancerPolystyrene (PS), Polyethylene (PE), Polyvinyl Chloride (PVC)Zhao et al., 2024[116]Pan et al., 2025 [117]4Gastric CancerPolystyrene (PS), Polyvinyl Chloride (PVC)Zhao et al., 2024 [116]5Cervical CancerPolyethylene (PE), Polypropylene (PP), Polyethylene-Polypropylene CopolymersZhao et al., 2024 [116]Xu et al., 2024, 2025 [118,119]6Breast CancerChlorinated Polyisoprene, Polypropylene (PP), Polystyrene (PS)Tian et al., 2025[120]7Penile CancerPolyethylene (PE), Polypropylene (PP), Polyvinyl Chloride (PVC)Wang et al., 2025 [121]8Prostate CancerPolyamide (PA), Polyethylene (PE), Polypropylene (PP), Polyethylene Terephthalate (PET), Polyvinyl Chloride (PVC), Polystyrene (PS)Deng et al., 2024 [122]
A recent World Health Organization report [97] emphasised how commonplace microplastics are in the natural environment and expressed worries about their susceptibility to and their effect on the health of humans [100– [102, 152, 153]. The production of pro-inflammatory cytokines is prompted to rise when NMs come into contact with immunological and epithelial cells [154]. Leukocyte recruitment into the wounded tissue is one way that the inflammatory response accomplishes its dual goals of removing destructive agents and repairing the damaged tissue or lacerations [155]. This would result in the production of ROS and reactive nitrogen species (RNS), which would negatively impact DNA, proteins, and lipids, ultimately causing tissue damage.
ROS and RNS may eventually harm stem cells that have been activated for tissue regeneration, and gene mutations may accumulate to become cancer stem cells [156]. If the injury is prolonged, chronic inflammation may result in damaging and repairing the injured tissue and leading to fibrosis and cancer [155]. Additionally, indicators to avoid autoimmunity and worsen immunological reactions, in addition to the epithelial-mesenchymal transition, would be elevated, along with other signalingpathways that promote infiltration and pro-metastatic immune responses [154, 157]. Moreover, as previously mentioned, DNA damages that are beyond repair can result in mutations that are critical to the start of carcinogenesis [158]and serve as an early indicator of the carcinogenic potential [103].
The role of microplastics and nanoplastics in cancer initiation and progression is an emerging field of research. Despite their widespread environmental presence, the cellular mechanisms by which MPs and NPs influence carcinogenesis remain poorly understood. Recent studies have primarily focused on understanding how these particles enter cancer cells, the pathways they trigger, and their impact on gene expression. However, there is still a limited understanding of how MPs and NPs influence key oncogenic processes, including cell proliferation, inflammation, oxidative stress, and metastasis. This section aims to provide an overview of in vitro studies that have explored these mechanisms across various cancer cell lines (Fig. 5).
Fig. 5Schematic Representation of Microplastics (MPs) and Nanoplastics (NPs) Interacting with Different Cancer Cells and Their Associated Proteins. This figure illustrates how microplastics (MPs) and nanoplastics (NPs) interact with various cancer cell types, mediating multiple cellular processes through specific protein interactions. In breast cancer cells, MPs/NPs promote metastasis and cancer progression by upregulating ANXA2 (Annexin A2), TMBIM6 (Transmembrane BAX Inhibitor Motif Containing 6), and PTP4A2 (Protein Tyrosine Phosphatase 4A2). In skin cancer, the activation of inflammatory responses is facilitated through IL-1β (Interleukin-1 beta) and NLRP3 (NLR Family Pyrin Domain Containing 3). In liver cancer, oxidative stress is triggered due to the dysregulation of SOD2 (Superoxide Dismutase 2) and mTOR (Mammalian Target of Rapamycin), while autophagic mechanisms are influenced by Ulk1 (Unc-51 Like Autophagy Activating Kinase 1). In colon cancer cells, MPs/NPs enhance autophagy via the mTOR/Ulk1 signaling pathway, promoting cellular survival. In gastric cancer, ASGR2 (Asialoglycoprotein Receptor 2) facilitates the internalization of MPs/NPs, contributing to carcinogenesis. In lung cancer, MPs/NPs upregulate TNF-α (Tumor Necrosis Factor Alpha), integrin α5β1, and NF-κB (Nuclear Factor Kappa B), leading to increased cell proliferation and metastasis. Centrally, the figure highlights the role of MPs/NPs in triggering multiple oncogenic signaling pathways, including NF-κB, mTOR, Wnt/β-catenin, and PI3K/Akt, which collectively enhance cancer cell survival, proliferation, and metastatic potential. The crystal structures of the interacting proteins were retrieved from the Protein Data Bank (PDB), including IL-1β (PDB: 1HIB), NLRP3 (PDB: 2NAQ), NF-κB (PDB: 1A3Q), integrin α5β1 (PDB: 4WK2), TNF-α (PDB: 1TNF), ASGR2 (PDB: 8URF), Ulk1 (PDB: 6QAS), mTOR (PDB: 4JSV), SOD2 (PDB: 8VJ8), PTP4A2 (PDB: 5K22), ANXA2 (PDB: 1W7B), and TMBIM6 (AlphaFold AF-P55061-F1). Abbreviations: ANXA2: Annexin A2, TMBIM6: Transmembrane BAX Inhibitor Motif Containing 6, PTP4A2: Protein Tyrosine Phosphatase 4A2, mTOR: Mammalian Target Of Rapamycin, NLRP3: NLR Family Pyrin Domain Containing 3, TNF-α: Tumor Necrosis Factor Alpha, ASGR2: Asialoglycoprotein Receptor 2, Ulk1: Unc-51 Like Autophagy Activating Kinase 1
Forte et al. first reported that gastric adenocarcinoma (AGS), when exposed to polystyrene nanoplastics (PS-NPS, 10 µg/ml, 44 nm) for one hour, resulted in the upregulation of the proinflammatory cytokines, namely IL-8, IL-6 and IL-1β [159]. Furthermore, the PS-NPs also slightly elevated the expression of the c-Myc oncogene. It should be noted that c-Myc has a strong connection to the metabolic changes carried out by transformed cells, such as glycolysis stimulation, biosynthesis of rRNA and protein, and mitochondrial biogenesis [126]. Furthermore, it was reported that PS-NPs can promote the oncogenic properties in several gastric cancer cell lines, such as AGS, MKN1, MKN45, NCI-N87, and KATOIII [160]. Moreover, the PS-exposed NCI-N87 cells were found to induce tumors in BALB/c mice. The whole transcriptomic analysis of the gastric tissues from the mice exposed to PS-NPs revealed the overexpression of Asialoglycoprotein Receptor 2 or ASGR2, and depletion of this gene in GC cell lines resulted in the increased susceptibility to certain anticancer drugs like bortezomib, trastuzumab and paclitaxel. Thus, ASGR2 emerged as a convincing marker that can induce oncogenic properties as well as multidrug resistance in MP-induced gastric cancer.
In a comprehensive study with human lung alveolar epithelial cells, A549, Xu et al. (2019), reported that the PS-NPs (25 nm and 50 nm sizes) significantly up-regulated the levels of proinflammatory cytokines such as IL-8, NF-κB, and TNF-α [160]. In an interesting finding, Han et al., revealed that integrin α5β1 facilitates the internalization of PS-NPs in lung cancer cells, which in turn triggers oxidative stress and inflammation [161]. The study by Cheng W et al., revealed the adverse effects of PS NPs in in vitro 3D model, using the liver organoids (LOs) generated from human pluripotent stem cells [162]. Additionally, after 48 h of exposure, the organoids made from H1 stem cells of human embryos treated with polystyrene microplastics (PS-MPs) demonstrated a dose-dependent rise in inflammatory biomarkers COL1A1 and IL-6 [163]. In the study Cox et al., 2019 the exposure doses of microplastics (MPs) in drinking water were set at 100 µg/L and 1000 µg/L. Based on the recorded water consumption and body weight, both the low-dose and high-dose groups of mice had similar daily water intake (5–7 mL) and body weight (27 g). Taking 5 mL of water and 27 g of body weight as an example, the estimated MPs intake for the low-dose and high-dose groups was 0.5 µg/day and 5.0 µg/day, respectively. These amounts correspond to exposure doses of 18.5 µg/kg/day and 185 µg/kg/day. The higher dose approximates the lower end of human MPs consumption (175 µg/kg/day) in everyday life [23]. The enhanced oxidative stress and inflammatory response caused by PSMPLs, together with other study results, led the scientists to identify distinct adverse outcome pathways (AOP 220 and AOP 38, respectively) that indicated liver cancer risk and fibrosis risk. Because synthetic particles smaller in size than 150 μm may penetrate the gastrointestinal epithelium of mammals and cause systemic exposure, human beings can absorb these particles after consuming them. A smaller fraction (0.1%) of the aforementioned particles, which contain particles larger than 10 μm, are thought to be able to navigate through the blood–brain barrier and placenta as well as organs and cellular membranes [164]. Scientists estimate that only 0.3% of the particles in question will be absorbed. The analytical and technical difficulties in the extraction, characterisation, and quantification of micro-plastics and nano-plastics from ambient matrices have resulted in a paucity of evidence regarding their presence in the environment.
Three studies that employed cell transformation techniques to examine the possible carcinogenic risk of MNPLs in vitro were reported. In two of these, the mouse embryonic fibroblasts (MEF Ogg1-/-) were subjected to a scenario of chronic exposure aimed at repairing oxidised DNA base lesions. The experiments involved the exposure of relatively low doses of PS-NPs (0.05 μm; 25 µg/mL) over durations of 12 and 24 weeks [165, 166]. An array of cancer-related hallmarks, including the colonies developed in the anchorage-independent growth assay along with the acquiring of migration and invasion abilities, were reported by the authors to have increased synergistically following a period of twelve weeks of chronic exposure to the concurrent treatment with arsenic (2 µMAsIII), a known cancer-causing agent in humans [166]. In a study reported lower doses of PS-NPs (1 and 3 mg/kg body weight/day) were selected to represent environmentally relevant concentrations of nanoplastics. In addition, higher doses (6 and 10 mg/kg body weight/day) were included for investigation due to their association with large-scale industrial production [167]. Rafiee et al., did not observe neurobehavioral effects after oral exposure to PS (25 and 50 nM) at oral doses of 1, 3, 6, and 10 mg/kg/day for 35 days [168].
The same group also showed that early tumoral phenotypic biomarkers might be changed by being subjected to the same NPs over a longer duration of time (24 weeks) [165]. Significant alterations in stress-response-related genes were detected, including the notable upregulation of Gstp-1 and downregulation of Sod1, Sod2, Pgp, Nrf2 and Keap. Furthermore, a disruption in a cluster of microRNAs closely associated with the oncogenic process was observed, encompassing miR-203, miR-34a, miR-502, miR-218, miR-210, miR-200a, miR-199b, miR-155, miR-148b, miR-135b, miR-96, miR-30c, miR-30d, miR-25, miR-23a, and miR-2, respectively. The cells treated with PS-NPs for 24 weeks resulted in an aggressive tumoral phenotype, which included elevated capacity of invasion, alterations in pluripotency markers (downregulated Sox2 and upregulated Oct3/4, Notch2, Nanog, and Klf4), and the creation of tumorspheres. Moreover, a notable increase was observed in the number of colonies capable of proliferating in soft agar, alongside enhanced cellular migration capability. Conversely, Kim et al. investigated carcinogenicity-associated endpoints in human gastric cancer cell lines KATO III, NCI-N87, MKN1, and AGS following a 4-week subjection with 8.61 × 10^5^ particles/mL of PSMPLs (9.5–11.5 μm) [169]. All of the cell lines saw enhanced rates of migration and proliferation after being exposed, and all but NCI-N87 cells experienced induction of invasion. Following the PSMPLs treatment, the examined cell lines showed an increase in the expression of the CD44 marker. It has been suggested that CD44 + cells are human gastric cancer stem cells. Additionally, the scientists showed that all of the chosen cell lines developed resistance to various anticancer medications as a result of exposure to PSMPLs.
In a recent study, Park et al.(2023) demonstrated that polypropylene MPs induce metastatic features in human breast cancer cells [169] and also pointed out the differential gene expression in MP-treated cells using a whole transcriptomic approach. They reported that after 24-hour incubation with PP-MPs in MDA-MB-231 cells, there was a notable alteration in cell cycle-related genes, and additionally, a significant increase in the secretion of the pro-inflammatory cytokine IL-6 from the cancer cells was observed. The RNA-Seq analysis of PPMP-treated MDA-MB-231 cells revealed that the expression of proliferation-related markers such as TMBIM6, AP2M1, and PTP4A2 were significantly up-regulated, while the expression of the antitumor gene FTH1 was markedly reduced [170]. TMBIM6 and PTP4A2 are well known for their tumor-prmoting roles in several carcinomas [171, 172]. They came forward with another interesting finding, that the noncancerous breast epithelial cells MCF-10 A did not acquire any oncogenic trait upon exposure to the PPMPs. A study conducted by Schnee et al. examined the cellular absorption and biological impacts of PS-MPs and NPs in human breast epithelial cells (M13SV1) and human breast cancer cell lines, encompassing triple-negative breast cancer (TNBC) cells (HS578T and MDA-MB-231) [150]. The research revealed that PS-MPs of different sizes (0.5 μm, 1.0 μm, and 4.5 μm) were absorbed by both normal and malignant breast cells depending on dosage, size, and cell lines. The most significant absorption was recorded in the aggressive MDA-MB-231 TNBC cells, whereas the minimal uptake was noted in normal breast epithelial cells. The absorption of MPs was not influenced by cell size, suggesting the participation of active endocytic mechanisms. Functionally, although PS particle treatment did not markedly affect colony or mammosphere formation (indicators of stemness), it did elicit moderate yet consistent effects on cell proliferation and migration in breast cancer cells, particularly at elevated particle concentrations. The effects were more apparent in MDA-MB-231 cells than in normal breast epithelial cells. The enhanced migratory ability of breast cancer cells in the presence of MPs raises concerns regarding their potential function in facilitating metastasis.
In the offspring of pregnant and female nursing mice, Maternal exposure to PS-NPs during gestation and lactation was found to impact neural stem cell function, alter neural cell composition, and affect brain histology. The findings indicated that PS-NP particles transferred from mother to offspring resulted in increased brain and body weight in postnatal progeny at doses ranging from 10 to 500 µg/day, with the most pronounced effects observed at 500 µg/day. However, at higher exposure levels (500–1000 µg/day), there was a significant reduction in the number of proliferating cells and nestin-positive progenitor cells—nestin being a specific marker for neural stem cells. Additionally, neurotoxic effects were evidenced by acetylcholinesterase (AChE) inhibition and elevated lipid peroxidation (LPO) in the brain, highlighting the potential of microplastics to induce oxidative stress and impair neurological function [173].
The selective oncogenic modulatory effects of the MPs were further demonstrated by Y Wang et al., in their recent findings [174]. Two types of skin squamous cell carcinoma cell lines (SCL-1 and A431) were employed to examine microplastics’ effects on skin cancer. Results revealed that microplastics infiltrated the carcinoma cells, accelerated cancer cell proliferation, and elevated mitochondrial reactive oxygen species (ROS), leading to the subsequent activation of NLRP3 inflammasome. Additionally, normal skin cell models (HaCaT cells) exposed to microplastics exhibited NLRP3-mediated inflammation and cell death. This study underscores the potential of microplastics to act as a double-edged sword as they can promote tumor proliferation of skin cancer cells and also induce damage to healthy skin cells [174].
A series of investigations have shown the genotoxic consequences of exposure to MPs utilising a variety of genotoxicity endpoints, pertinent cell lines, varying MP sizes and concentrations, and varying exposure durations. After PS-NPs were added to human hematopoietic cell lines, the comet assay was used to evaluate DNA damage (which might have been caused by oxidative processes or not) in a cell-line-specific, time- and concentration-dependent manner [175]. It was shown that after 24 and 48 h of exposure, Raji-B cells underwent treatment with PS-NPs (50 nm, 5–50 µg/mL) had a noticeable increase in a dose-dependent manner in DNA damage; however, oxidative DNA damage (ODD) was only seen at the highest dosage (50 µg/mL) and following exposures spanning 24 h. In TK6 cells, solely ODD was found in a time- and dose-dependent manner. In contrast, PS-NP-treated THP1 cells did not exhibit any DNA damage, regardless of the doses or time intervals used. The varying absorption of PS-NPs and the possible production of ROS may be connected to the varying cell susceptibility to genotoxic chemicals. Comparably, another study used the comet assay to sort different cell types from whole blood cells (WBC) such as PMNs (polymorphonuclear cells), monocytes, and lymphocytes acquired from various donors and evaluated the DNA damage specific to individual cells caused by ex vivo exposure to varying concentrations of PS-NPs (0.05 µM) [176]. After 24 h of exposure, PS-NPs significantly increased the proportion of DNA in the tails of monocytes (100 µg/mL) and PMNs (50 and 100 µg/mL), but not in lymphocytes or the whole WBC population.
In the in vitro human intestinal barrier models (consisting of a culture of differentiated Caco-2/HT29 intestinal cells and a triculture containing Caco-2/HT29/Raji-B cells), exposure to various concentrations (ranging from 1 to 100 µg/mL) of PS-NPs (with an average size of approximately 50 nm) did not result in a significant increase in cellular-specific DNA damage. This was determined through comet assay analysis after 24 h of exposure. Despite the findings showing a clear absorption of PS-NPs, the absence of DNA-damaging effects may be explained by the negligible formation of ROS [93]. The sole in vitro investigation showcasing findings on the formation of MPs during an extended exposure used undifferentiated Caco-2 cells subjected to pristine PS-NPs (50 nm; 0.26 µg/cm^2^) for 24, 48, 72, and 96 h, as well as on a weekly basis until week 8. After two weeks of exposure, internalisation peaked, and PS-NPs continued to accumulate inside the cells at a steady rate throughout the next weeks [82]. Nevertheless, the comet test did not reveal any DNA damage in undifferentiated Caco-2 cells treated with PS-NPs (50–100 nm; 10 and 100 µg/mL) for eight weeks. However, the expression of a couple of genes linked to oxidative stress (HO1 and SOD2) increased in proportion to the dosage. In an alternate study, the comet assay was used to assess the genotoxic effects of PS-NPs (0.05 μm, 25 µg/mL) and co-exposure of PS-NPs with sodium arsenite (AsIII) (25 µg/mL / 2 µM) on mouse embryonic fibroblasts that are susceptible to oxidative damage (Ogg1 /π) [166]. After a 12-week chronic treatment with PS-NPs alone, the findings indicated a considerable increase in DNA damage caused by both oxidative and non-oxidative processes.
A pivotal work by Brynzak-Schreiber et al. provided insight into the dynamics of MPs in human colorectal cancer cell lines, emphasizing essential factors pertinent to cancer progression [177]. This study emphasizes the dual difficulties related to MPs in cancer (i) their capacity to persist and bioaccumulate in cancerous tissues, and (ii) their possible function as pro-metastatic agents via influencing cancer cell migration and intercellular dispersion during proliferation. The study revealed that PS particles of varied dimensions (0.25 μm, 1 μm, and 10 μm) are efficiently absorbed by various CRC cell lines (HT29, HCT116, SW480, and SW620), with smaller particles exhibiting increased cellular uptake. The uptake was significantly influenced by particle size, concentration, exposure duration, and specific properties of the cell line, with HCT116 cells exhibiting the greatest internalization efficiency [177]. Also, in 3D tumor spheroid models, MPs preferentially concentrated in non-proliferative zones and necrotic cores, whereas proliferative regions exhibited a reduced presence of particles, presumably due to dilution from cellular division. Vascular endothelial damage is a significant toxic effect associated with microplastics and nanoplastics (MPs/NPs). Research has shown that 100 nm PS-NPs are internalized by vascular endothelial cells, where they induce autophagosome formation and disrupt autophagy flux. In contrast, 500 nm PS-NPs primarily adhere to the cell membrane, leading to structural damage of the membrane [178].
Mice and rats exposed to MNPLs were observed to have in vivo inflammatory reactions in various investigations. Every three days for up to twenty-four days, Lu and colleagues administered PSMPLs (1–5 μm; 300 µg in 20 µL of saline for each animal) or a solution of saline (control) to intranasally healthy Female BALB/c mice with allergic asthma, induced by House Dust Mite (HDM) [179]. In lung portions of the MPLs-exposed groups, a buildup of plastic particles was seen co-localising with macrophages. Together with MPL-loaded macrophages, it was also shown that the airspace of the lungs of HDM-induced allergic asthmatic mice, whether or not they received MPL treatment, had a significant attraction of inflammatory cells, including macrophages, plasmocytes, neutrophils, lymphocytes, and eosinophils. Furthermore, compared to healthy mice who received saline, there were more eosinophils in the bronchoalveolar lavage (BAL) of mice subjected to MPLs. As a result, MPL exposure increased the degree of inflammation in allergic mice and caused the migration of inflammatory cells to the lungs of healthy mice. Additional tests were carried out using plasma and BAL to ascertain the levels of immunoglobulin E (IgE) and IgG1, as well as the cytokines TNF-α, IFN-γ, IL-33, IL-17 A, IL-13, IL-10, IL-5, and IL-4. When healthy mice were exposed to MPLs, their levels of TNF-α were higher than those of the control group. When compared to the healthy control group, asthmatic mice exposed to both MPLs and those not exposed had considerably higher levels of IgE and IgG1; however, there were no distinctions observed among the asthmatic groups. Crucially, in contrast to the non-treated control, healthy mice exposed to MPLs had higher IgG1 levels. PSMPL administration generally causes proinflammatory effects in healthy mice but does not change the expression of immunoglobulins and cytokines in asthmatic animals. Moreover, the transcriptome analysis showed that the injection of MPLs changed immune activation, cell cycle regulation, and signalling pathways like the MAPK cascade. The ASC-inflammasome pathway involving NLRP3, ASC, and cleaved Caspase-1 (Cas-1) was also shown to be upregulated in the mid colon of ICR mice following oral treatment of PSMPLs (0.5 μm; 10, 50, and 100 µg/mL; 0.5 mL/day) every day for two weeks. This observation was made by Choi and colleagues [179]. Additionally, the scientists connected the reaction to the production of proinflammatory genes through the activation of NF-κβ. The expression of TNF-α, IL-1, IL-6, IL-10, TGF-β1, NF-κβ, and IL-1 was measured to demonstrate that. In comparison to the untreated control group, the data clearly demonstrated dose-dependent increases in mRNA levels for all the cytokines in the PSMPLs-treated mouse groups. Li and colleagues conducted a study on the blood levels of several cytokines, such as RANTES, IP-10, IL-9, IL-6, IL-5, IL-2, G-CSF, and IL-1α, in C57BL/6 mice that were fed diet containing polyethenemicroplastics (10–150 μm; 6, 60, and 600 µg per animal) daily for a period of five weeks [180]. The groups of mice administered PEMPLs showed a considerable rise in IL-1α expression. After the PEMPLs were exposed, the expression of the other cytokines under analysis either remained unchanged or even reduced. Additional indicators of inflammation, such TLR4, AP-1, and IRF5 expression, or the presence of plasma cells and lymphocytes in the mice duodenum given 600 µg PEMPLs, demonstrated the production of intestinal inflammation.
Liver inflammation was detected in C57BL/6 mice under both normal diet and high-fat diet (HFD) conditions, following administration of PS-NPs (41.54 nm; 10 and 50 µg/mL in 100 µL of PBS per mouse) via the tail vein every 3 days for a duration of 15 days [92]. IFN-γ, IL-2, IL-12, IL-1β, and TNF-α expression levels showed that PS-NP-treated mice in the HFD mouse groups had more significantexpression of the inflammatory genes. Interestingly, liver tissue from HFD animals given 10 µg/mL PS-NPs showed substantial collagen deposition. The noteworthy ability of PS-NPs to cause fibrosis in the HDF group of mice was validated by the enhanced expression of COL1a and α-smooth muscle actin (α-SMA), both of which are significant players in fibrogenesis. These outcomes align with the previously documented elevated concentrations of two indicators of hepatic cell damage, amino-transferases ALT and AST, in HFD mice with 10 µg/mL PS-NPs. Hepatocellular carcinoma, liver cirrhosis (fibrosis), and chronic hepatitis (inflammatory response of the liver tissue) have all been associated with these biomarkers. In a separate investigation [181], researchers noted a notable increase in the expression of fibronectin, Collagen I, α-SMA, p-β-catenin, TGF-β, Wnt in the cardiac tissue of male Wistar rats following daily ingestion of 5 and 50 mg/L of PSMPLs (0.5 μm) for 90 days through drinking water. Additionally, the highest dosage led to elevated expression levels of β-catenin and Collagen III. In the heart of treated rats, there was a notable rise in both fibronectin deposition (5 and 50 mg/L PSMPLs) and collagen deposition and hyperplasia (50 mg/L PSMPLs). After 90 days of exposure, a buildup of PSMPLs was also discovered inside cardiomyocytes. After 90 days of exposure to the identical PSMPLs (0.5 μm; 0.015, 0.15, and 1.5 mg/day/rat in drinking water), similar outcomes were seen in the ovaries of female Wistar rats. Moreover, Wnt and TGF-β expression rose in female rats at 0.15 and 1.5 mg/day PSMPLs, although fibronectin, Collagen III, Collagen I, α-SMA, β-catenin, p-β-catenin expression increased only after the highest dosage treatment [182]. Furthermore, some groups have connected PSMPL-induced fibrosis to oxidative stress-induced cell death, which in turn triggers the production of the identified cytokines [181, 182].
However, the most confirmatory demonstration of MP-induced carcinogenesis in the animal model has been reported in a very recent study by Chen G et al. [160]. They reported that PS-NPs can promote ovarian cancer development in mice and also enhance oncogenic properties in several gastric cancer cell lines, such as AGS, MKN1, MKN45, NCI-N87, and KATOIII. Using the cutting-edge whole transcriptomic technique, they also highlighted the underlying mechanism. The BALB/c mice were used in this study and injected with ovarian cancer cell line HEY to develop tumours. Interestingly, the tumor-bearing mice that were exposed to PS-NPs showed enhanced oncogenic properties with greater tumour mass and volume. The RNA seq data for the NP-exposed ovarian cancer cells and also mice tumors confirmed the alteration of the genes responsible for the modulation of the tumor microenvironment and immune responses [160]. Very interestingly, they observed that treatment with PS-NPs enhanced proliferation, migration, and invasiveness in AGS, MKN1, MKN45, NCI-N87, and KATOIII cells. Moreover, the PS-exposed NCI-N87 cells were found to induce tumors in BALB/c mice. The whole transcriptomic analysis of the gastric tissues from the mice exposed to PS-NPs revealed the overexpression of Asialoglycoprotein Receptor 2 or ASGR2, and depletion of this gene in GC cell lines resulted in the increased susceptibility to certain anticancer drugs like bortezomib, trastuzumab and paclitaxel. Thus, ASGR2 emerged as a convincing marker that can induce oncogenic properties as well as multidrug resistancein cancer cellsbecause of the exposure.
Recent evidence suggests a critical link between microplastics (MPs), particularly polystyrene nanoplastics (PS-NPs), and the progression of colitis-associated cancer (CAC), a severe complication of ulcerative colitis (UC). The study by Tian et al. (2025) provides the first comprehensive demonstration of how PS-NPs exacerbate CAC development in vivo and in vitro by disrupting lipid metabolism, inducing oxidative stress, and causing DNA damage [120]. In an AOM/DSS-induced murine model of CAC, chronic exposure to PS-NPs resulted in increased tumor burden, heightened reactive oxygen species (ROS) levels, DNA damage, and histological features of aggressive tumor growth. PS-NPs exposure activated the PI3K/AKT/mTORsignaling pathway, a key regulator of cellular metabolism, proliferation, and survival. Notably, this activation was associated with mitochondrial dysfunction and downregulation of fatty acid oxidation enzymes such as CPT1A and ATGL, underscoring the role of disrupted lipid metabolism in CAC pathogenesis. Further, 16 S rRNA sequencing revealed that PS-NPs altered gut microbiota composition, with a significant increase in colitogenicAllobaculum species and a decrease in beneficial Lactobacillus populations, contributing to gut dysbiosis and promoting tumor progression.
Recent data highlight the impact of MPs on altering the gut microbiome, promoting dysbiosis associated with adverse metabolic and carcinogenic consequences [129, 183]. Numerous preclinical and clinical studies demonstrate that MPs and NPs substantially alter the composition and diversity of the gut microbiota, leading to dysbiosis. Ke et al. observed that children exposed to microplastics exhibited significant changes in their gut bacteria, particularly in the abundance of Alistipes and Parabacteroides species [184]. Li et al. reported a substantial increase in the populations of Parabacteroides and Staphylococcus species after MP exposure [185], however, Lu et al. observed a notable decline in beneficial faecal microorganisms, including α-Proteobacteria and FirmicutesSp [186].
A landmark study conducted by Tian et al. demonstrated that chronic exposure to polystyrene microplasticssignificantly altered the intestinal microbiota in mice, characterised by an increase in Allobaculum species and a concurrent decline in beneficial microbes, such as Sp. [120]. Certain species of the Allobaculum genus, particularly Allobaculummucilyticum and Allobaculumfili, are significantly linked to inflammatory bowel disease (IBD) [187]. These bacteria may compromise the gut’s protective mucus barrier, exacerbating mucosal inflammation [188]. Chronic inflammation, a hallmark of inflammatory bowel disease (IBD) such as ulcerative colitis and Crohn’s disease, is a proven risk factor for colitis-associated cancer (CAC) [189, 190]. In contrast, multiple studies have highlighted the anticancer effects of Lactobacillus species in reducing the progression of colitis-associated cancer (CAC) or colorectal cancer (CRC) [191, 192]. Consequently, MP-induced alterations promoting dysbiosis, particularly the proliferation of pathogenic taxa and the diminishment of beneficial bacteria, may significantly elevate the likelihood of CAC formation [120]. Chronic exposure to PS-MP mechanistically increases tumor burden and oxidative stress, hence activating essential oncogenic signaling pathways, including the PI3K/AKT/mTOR pathway in colonic tissues [120]. Further evidence indicates that microbiota alterations induced by MPs can negatively affect Wnt/β-catenin signaling. Long-term MP consumption reduces gut-derived metabolites such as hypoxanthine, hence diminishing Wntsignaling in host stem cells, which is essential for preserving gut epithelial homeostasis [129]. Furthermore, microbial compounds like lipopolysaccharides (LPS), which traverse a damaged gut barrier, can persistently activate Toll-like receptors and NF-κBsignaling pathways. This chronic inflammatory stimulation fosters intestinal and hepatic inflammation, synergistically activating metabolic and inflammatory pathways (such as PI3K/AKT, Wnt/β-catenin, and NF-κB), ultimately promoting cancer.
Evidently, widespread attention has been given to immunotoxicity and cancer development caused by MPs/NPs. Studies showed that MPs-NPs cause an inflammatory response by producing excessive ROS production that activates the antioxidant system through the NRF-2/KEAP-1 pathway [193]. Subsequently, the inflammatory NFκBsignaling pathway activated phosphorylation of the MAP kinase signaling pathway, which in turn activated nuclear-bound ERK and p38. This further phosphorylated oncogenic signaling genes/proteins cascade, which in turn reduced apoptosis and the mechanism of cell death. At the same time, Akt phosphorylation resulted in the loss of control over FoXO1, a crucial gene that controls glucose metabolism, the cell cycle, and apoptosis. Furthermore, via ERK-PPARγ pathways, the activated ERK encouraged lipid buildup as well, which induced lipotoxicity. Consequently, the activation of the NFκB and MAPK signaling pathways by MPs-NPs-mediated ROS may represent a possible signaling molecule pathway that promotes oncogenesis. Cytokines are crucial mediators of inflammation, coordinating both acute and chronic inflammatory responses through a complex network of interactions. Pro-inflammatory chemokines, mainly generated by various cells, attract leukocytes to areas of infection or damage [194] and [191]. Additionally, research demonstrates that MPs can modify the mRNA expression and protein concentrations of immune-related cytokines in various species. Consequently, brief exposure to MPs may trigger inflammation in mammalian cells, zebrafish larvae, and bacteria, too [195]. The NF-κB pathway, a key regulator of pro-inflammatory signaling, is well-known for its regulation of genes related to inflammation, including cytokines and adhesion molecules. Toll-like receptors (TLRs), recognized for their stimulation by pathogen-associated molecular patterns (PAMPs), play a significant role in initiating inflammatory pathways. Although these receptors have structural variations, they display similar signaling activities when confronted with inflammatory triggers, including MyD88 recruitment, activation of the IKK complex, and subsequent stimulation of NF-κB. It is hypothesized that TLRs could detect danger signals from MPs, triggering MyD88-dependent pathways that lead to NF-κB activation, which in turn enhances pro-inflammatory transcriptional programs. Additional studies into the recognition mechanisms of danger signals triggered by MPs are crucial for a deeper understanding of human immune reactions. Under normal circumstances, NF-κB remains in an inactive form in the cytoplasm due to its association with an inhibitor, IκB [196]. When activated, IκB is phosphorylated by the IKK complex, enabling NF-κB to enter the nucleus. The movement of the activated P65 subunit into the nucleus is directly linked to the increased expression of pro-inflammatory factors, including several cytokines (IL-1, IL-6, TNFα, IL-8, and IL-12, among others) and chemokines (CCL2, CCL5, CXCL9, 10, 11, and CXCL16, among others). In quintessence, NF-κB acts as a molecular regulator that triggers the expression of IL-8, which in turn contributes to the inflammatory cascade [197]. The relationship between inflammation and oxidative stress is significant. Typically, the immune system regulates intracellular redox balance and the production of antioxidant enzymes to maintain homeostasis. Oxidative stress, however, can result from an imbalance in the production of ROS and antioxidant enzymes. According to studies, MPs dramatically increase the formation of ROS in vivo and upregulate the mRNA levels of genes linked to antioxidant enzymes and ROS creation. Lipid peroxide level and antioxidant enzyme activity were also significantly changed, suggesting that MPs caused oxidative stress. Intracellular ROS levels rise as a result of oxidative stress brought on by MPs adhering to the cell membrane. Zhou et al. (2011) [198] noted a similar mechanism in which asbestos particles activated NADPH oxidase, causing “frustrated” phagocytosis and the production of ROS. This implies that MPs have an impact on phagocytes, including fibroblasts.
Recognizing the nascent but significant link between microplastic exposure and cancer, we outline several key avenues for future research and policy – aimed at translating mechanistic insights into real-world
A top priority is to establish reliable biomarkers of MP/NP exposure and effect in humans. This could include detecting and quantifying microplastics (and their associated chemical signatures) in patient samples as an exposure metric, or identifying molecular fingerprints (such as cytokine profiles or gene expression changes) that signify chronic MP/NP insult. For example, recent analyses have detected microplastics in neonatal meconium and placenta, serving as alarming indicators of prenatal exposure [114]. Developing standardized assays to measure microplastic load in blood or tissues could enable epidemiological studies to correlate exposure levels with cancer incidence [19]. Such biomarkers would also allow clinicians to identify high-risk individuals (e.g. people in heavily polluted environments or certain occupational settings) and monitor the effectiveness of exposure-reduction strategies. Furthermore, molecular biomarkers (like persistent inflammatory or oxidative damage markers) in tumor or adjacent tissues might reveal whether microplastic-induced pathways are active in a given patient’s cancer, potentially informing personalized risk assessments.
MPs/NPs can infiltrate the human body through the food chain and contaminated environments. The main ways they can enter the body include ingestion, inhalation, and skin contact. The biggest concern lies in the limited understanding of how environment-related exposure to microplastics affects human health. For instance, chemical additives might be incorporated during the production of plastic items. Fine atmospheric particles, such as PM2.5 (particulate matter with a diameter of ≤ 2.5 μm), can carry microplastics and may facilitate their transfer to living organisms following ingestion [199]. Although a few studies have investigated this topic, there is a pressing need for more research on the contamination by microplastics and its potential health implications. Recent findings showing the presence of microplastics in the human body have alarmed the scientific community, as our knowledge of human exposure is still sparse, and the health impacts are not well understood [200]. Microplastics have been identified in over half of the human organ systems and can be categorized by their shape, color, size, and the types of polymers from which they are made. The primary exposure routes appear to be inhalation and ingestion, leading to their movement into various organ systems. A recently published article by Roslan et al. has shown the screening and detection of MPs in human tissues. Moreover, the article has shown the abundance of microplastics in various human tissues and fluids as well. However, the correlation between microplastics and their sources, as well as the links to adverse health effects, has yet to be thoroughly investigated. It is evident that more research is mandatory to understand the long-term effects of microplastics on human health and to develop effective strategies for mitigating exposure. More investigations are necessary to comprehend the long-term implications of microplastics on health and to develop strategies for reducing exposure. Future studies should implement strict contamination control measures during sample handling and processing to limit atmospheric microplastics contamination [201]. Currently, there is no standardized protocol approved for the clinical detection of microplastics in human samples. However, Huang et al. (2022) proposed using laser infrared imaging spectroscopy and Fourier-transform infrared microscopy to analyzesputum samples and assess microplastics in the respiratory tracts of patients with various respiratory conditions [202].
Research indicates that MPs can disrupt normal metabolic processes, provoke oxidative stress, and elicit neurotoxic, genotoxic, and inflammatory responses. Despite this, our understanding of the toxicity associated with microplastics remains limited. Key challenges ahead include elucidating the toxicological mechanisms of MPs, both individually and in conjunction with other environmental factors, as well as determining how MPs are absorbed by intestinal cells and how they translocate into the bloodstream and target tissues. Investigations into immune response modulation have focused on transcription factors, notably NF-κB, which plays a crucial role in inflammatory responses and is expressed in macrophages to initiate inflammation [202]. Bergamaschi et al. (2023) conducted a thorough analysis of biomarkers related to inflammation, oxidative stress, and genotoxicity, revealing significant findings through in vitro studies with human cells, including cancer cell lines, exposed to MPs/NPs. Their research highlighted both increases and decreases in various reactive oxygen species (ROS) and inflammation-related markers, such as SOD, GSH, CAT, GST, IL-6, IL-8, IL-1β, TNFα, IL-10, and NF-κB. Additionally, Roursgaard et al. (2022) investigated the toxicity of different sizes and types of MPs on various animal tissues. They found that exposure to polypropylene (PP) (0.08–0.25 μm) and polyethylene terephthalate (PET) (0.2–0.6 μm) led to a dose-dependent increase in DNA damage within hepatocellular carcinoma and colorectal adenocarcinoma epithelial cell lines after exposure to PET when compared to control cells. Consequently, the biomarkers study could serve as a valuable foundation for examining the impacts of MPs and NPs in occupational contexts, ultimately aiding in the understanding of their negative effects on human health, including cancer risk [203, 204]. Thus, the biomarkers are not just academic benchmarks; they represent a critical starting point for investigating the effects of MPs and NPs in occupational settings. Ultimately, the understanding of the adverse health implications posed by MPs/NPs, including their potential links to cancer. The inhibition of adaptive anticancer immunity also plays a role in shaping the tumor microenvironment (TME). MPs/NPs facilitate the differentiation of regulatory T cells (Tregs) and Th17 cells, which are linked to T cell exhaustion. They also enhance the expression of various cytokines and immune checkpoint proteins, such as IL-1β, IL-17, CTLA-4, and PD-1, within the colon. This cascade results in the establishment of an inflamed and immunosuppressive TME, thereby advancing colon tumor development. Considering the prolonged presence of MPs in the human body, the resulting inflammatory cytokines may contribute to a cancer-favorable inflammatory environment [132]. Furthermore, Zhang et, al. (2025) showed that MPs were detected in breast cancer patient tissues, resulting in mitochondrial damage and inducing autophagy in breast cancer cells as well. Subsequently, the expression and accumulation of IL-17 were found to be significantly increased in breast cancer tissues and cells upon exposure to MPs/NPs. Thus, the IL-17-mediated signalling pathway can be targeted in MPs-induced carcinomas [149]. However, anti-IL-17 therapies, which include medications that inhibit the function of IL-17, can be used to treat various disorders. While, it is not a direct remedy for MPs/NPs related disorders, IL-17 is involved in inflammation, making it a potentially relevant factor for studying the effects of MPs on health. The current knowledge regarding the toxicity of MPs/NPs is inadequate, resulting in significant challenges when evaluating their effects on human health. This limitation arises from several factors, including the insufficient sensitivity and specificity of existing detection methods for MPs and NPs. Furthermore, laboratory investigations assessing the health effects of MPs often fail to replicate real-world exposure conditions. Currently, there are no clinically validated detection strategies for MPs and NPs, and much of the existing research focuses primarily on short-term or acute exposure effects. Additionally, there is a lack of exploration into how MPs and NPs differentially impact vulnerable groups, particularly children and the elderly, while potential health risks associated with chronic or low-dose exposure are frequently overlooked. The scarcity of long-term studies examining the chronic effects of MPs on human health is a notable knowledge gap. Research is also deficient in exploring the long-term health outcomes of MP exposure, with a significant absence of epidemiological data investigating the relationship between MP exposure and the onset of chronic diseases. Therefore, it is essential to conduct long-term cohort studies that systematically track participants’ exposure to various types and concentrations of MPs over time and assess their correlation with health issues, including inflammatory diseases and cancer [205, 206]. Research from both epidemiological and experimental perspectives highlights the pressing need for clinical studies to clarify the link between MPs and cancer. The issue is particularly critical in biomedicine, given that cancer continues to be the leading cause of death despite improvements in diagnostic and treatment options.
Thus far, much of the evidence linking MPs/NPs to cancer comes from laboratory models; there is a pressing need to extend these findings into human populations. Long-term, patient-centred studies should be undertaken to evaluate the real-world impact of microplastic exposure on cancer risk and outcomes. This entails large-scale epidemiological investigations tracking microplastic exposure (through environmental monitoring and biomarker readouts) alongside cancer incidence in diverse cohorts. Particular attention should be paid to high-exposure groups for instance, communities in areas with severe plastic pollution or workers in industries with heavy microplastic generation, to see if their cancer rates exceed expected baselines. Case-control studies analysing microplastic content in tumour tissues versus normal tissues of cancer patients could yield insight into whether tumours tend to accumulate these particles or if patients with certain cancers have higher body burdens of MPs/NPs. In addition to incidence studies, clinical research on cancer patients could examine whether those with higher microplastic loads have different disease trajectories or responses to therapy. Ultimately, this patient-centred approach will ground the mechanistic insights in public health reality, providing a scientific basis for risk assessment and policy.
As we elucidate the pathways by which microplastics promote cancer, these very pathways present opportunities for therapeutic intervention. One future direction is to explore drugs or lifestyle modifications that mitigate MP/NP-induced damage. For instance, if chronic MP exposure is shown to drive tumorigenesis via unregulated inflammation or oxidative DNA damage, anti-inflammatory agents or antioxidants could be tested for their ability to reduce these effects in high-exposure models or even in at-risk populations. There may be scope to repurpose existing anti-cytokine biologics (like IL-17 or IL-6 inhibitors) might counteract a microplastic-fueled inflammatory microenvironmentor drugs targeting the MP-driven oncogenic signalling.
Another consideration is how microplastics might influence cancer treatment outcomes. Early data suggest MPs/NPs can interfere with the absorption, distribution, metabolism, and excretion of anti-cancer drugs, potentially undermining therapy efficacy or increasing toxicity. Future research should investigate this interaction in vivo or clinically, for example, do patients or animals with high microplastic burdens respond differently to chemotherapy or immunotherapy and if so, how treatment regimens could be adjusted. On the other side, scientists are also investigating the use of engineered nanoplastics as drug delivery systems to improve cancer therapy. Harnessing the same properties that make environmental NPs so pervasive (high stability and carrier capacity), researchers have designed biodegradable polymer nanoparticles to carry chemotherapeutics or immunomodulators with enhanced targeting and controlled release [114].
While promising, this approach demands rigorous safety testing to ensure these therapeutic plastics don’t introduce new risks. In summary, future oncological research should aim not only to counteract the harmful impacts of inadvertent MP exposure but also to cautiously leverage the beneficial uses of plastic particles in the treatment regimes.
The emerging link between microplastics and cancer has significant implications for regulators and public health policymakers. If MPs/NPs are confirmed as carcinogenic or at least as facilitators of cancer, they warrant the same level of precaution and control as other environmental carcinogens. Regulatory agencies should proactively consider setting exposure limits for microplastics in air, water, and food, informed by toxicological data and cancer risk assessments. This could involve tighter regulation of industrial processes that release microplastics (e.g. textile fibers, tyre wear, cosmetic microbeads) and improvements in wastewater filtration and waste management to intercept particles before they enter the human food chain. On a broader scale, international and national bodies need to encourage source-reduction promoting biodegradable alternatives, expanding plastic recycling programs, and incentivizing manufacturers to minimize primary microplastic ingredients.
From a public health perspective, raising community awareness is paramount. Educating the public on simple measures (such as reducing single-use plastics, dust control in homes, and proper ventilation to lower indoor microfibers) can help individuals limit their exposure. Concurrently, healthcare providers might consider advising populations at risk about the potential dangers of chronic microplastic exposure as part of preventive health.
Ultimately, a coordinated effort between scientists, clinicians, and policymakers will be required to translate the burgeoning scientific insights into effective regulations and guidelines that protect populations from the long-term carcinogenic risks of microplastics.
A key limitation in current microplastics toxicology lies in the disconnection between experimental exposure levels and those encountered in real-world human settings. Many in vivo and in vitro studies utilize high concentrations of MPs, often exceeding realistic environmental or dietary exposures, to elicit measurable responses within limited timeframes. However, humans are chronically exposed to low doses of MPs through ingestion, inhalation, and dermal contact, with estimated intakes ranging from 0.1 to 5 mg per day depending on regional and lifestyle factors. Recent long-term studies have revealed that even low-level, chronic exposure may lead to significant biological effects, including oxidative stress, immune dysregulation, gut microbiome alterations, and tissue-specific inflammation. Therefore, future studies should be designed with toxicokinetic realism, incorporating dose–time matrices, cumulative tissue burdens, and non-linear dose–response assessments that reflect the chronic, low-level exposure profiles typical of human populations. Integration of these approaches with biomonitoring data, longitudinal epidemiological studies, and real-world environmental sampling will be essential to advance risk assessment frameworks and guide regulatory thresholds. Bridging this gap is imperative to establish clinically and environmentally relevant exposure–effect relationships, particularly for cancer risk assessment. Incorporating these parameters into experimental design, alongside epidemiological and biomonitoring data, will help improve the translational relevance of MP toxicity studies and support more accurate human health risk assessments.
Our review builds upon and significantly extends the current state-of-the-art by Deng et al., [114], which provided a pioneering framework that elegantly outlined the broad biological mechanisms, including inflammation, oxidative stress, and endocrine disruption through which microplastics may modulate cancer risk. Moreover, their study brought forth the novel concept of utilizing MPs/NPs as drug delivery vehicles in cancer therapeutics, highlighting the duality of their potential risks and benefits. While acknowledging and appreciating these valuable contributions, the present review advances this emerging field by integrating a more comprehensive and mechanistically detailed body of evidence that was not extensively addressed in prior literature.
Firstly, we incorporate newly available data delineating the abundance of MPs/NPs in human biological samples, including tumor tissues. Notably, recent studies have documented the presence of microplastics in human cancer tissues, thereby substantiating that humans are not merely environmental recipients but are directly exposed to these plastic particles.
Secondly, this review delves into a range of detailed in vitro studies that elucidate the cellular and molecular mechanisms through which MP/NP exposure drives cellular transformation, promotes oncogenic signaling, and modulates tumor-associated pathways.
Thirdly, we extend the discussion to in vivo experimental models, bridging the gap between in vitro observations and complex biological systems. Compelling evidence from animal studies demonstrates that chronic MP/NP exposure can accelerate tumor growth, promote metastatic dissemination, and alter the tumor microenvironment, thus reinforcing the translational relevance of these findings.
Thus, the accumulating evidence highlighted in this review demonstrates that MPs and NPs are not merely passive environmental pollutants but active modulators of the tumor microenvironment (TME). These tiny particles can breach cellular barriers, accumulate within cancer cells, and trigger oxidative stress, leading to DNA damage and mitochondrial dysfunction. Their presence disrupts normal cellular signaling, activating oncogenic pathways such as NF-κB, mTOR, Wnt/β-catenin, and PI3K/Akt, which promote uncontrolled proliferation, survival, and metastasis of cancer cells. Additionally, MPs/NPs enhance inflammatory responses, increasing the release of cytokines such as IL-1β, IL-6, and TNF-α, which further sustain a pro tumorigenic environment. Beyond the direct effects on cancer cells, MPs/NPs also reprogram the surrounding TME by modulating the behavior of immune cells, altering autophagic processes, and disrupting antioxidant defenses through proteins like SOD2 and Ulk1. The ability of MPs/NPs to engage with multiple cellular components, including ANXA2, TMBIM6, ASGR2, and PTP4A2, highlights their multifaceted impact on tumor biology (Fig. 6). These interactions collectively create a permissive environment for cancer initiation, progression, and metastasis.
Fig. 6Modulation of the Tumor Microenvironment by Microplastics/Nanoplastics (MPs/NPs). Following oral consumption, MPs/NPs undergo gastric deposition and bind to the asialoglycoprotein receptor 2 (ASGR2), initiating cellular internalization and triggering a cascade of pro-tumorigenic events. This interaction induces a chronic inflammatory response mediated by NF-κB activation, resulting in elevated secretion of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α). Concurrently, MPs/NPs disrupt redox homeostasis through mitochondrial ROS generation, creating oxidative stress that promotes DNA damage and genomic instability. The internalized particles activate key oncogenic pathways, including PI3K/AKT/mTOR signaling, while simultaneously suppressing autophagy regulators (ULK1, PTP442), collectively driving uncontrolled cellular proliferation through upregulation of cell cycle markers (Ki67, Cyclin D, Cyclin E). Furthermore, MP/NP exposure induces a cancer stem cell-like phenotype characterized by overexpression of stemness markers (Oct3/4, Notch2, Nanog, Klf4, CD44), which contributes to tumor initiation, progression, and acquired chemoresistance. The process is further amplified by dysregulation of oncogenic microRNAs (miR-21, miR-29d, miR-30d, miR-96, miR-210, miR-502) that modulate critical targets (ANXA2, TMBIM6, IGF-1R) within these pathways. Together, these mechanisms establish a permissive tumor microenvironment that facilitates epithelial oncogenic transformation, ultimately leading to malignant progression and reduced therapeutic efficacy
In conclusion, the mechanistic relationship between microplastic exposure and cancer development represents a complex and interdependent network of biological disruptions. The presence of microplastic and nanoplastic particles initiates cellular uptake and long-term retention within tissues, leading to elevated oxidative stress and the generation of reactive oxygen species. These reactive intermediates contribute to DNA damage and mutational events, triggering a cascade of chronic inflammation, immune dysregulation, epithelial barrier compromise, and microbiome alterations. These events, in turn, result in epigenetic modifications and the activation of oncogenic signaling pathways such as NF-κB, Wnt/β-catenin, and PI3K/Akt, collectively shaping a pro-tumorigenic microenvironment. Notably, these events contribute to the modulation of the tumor microenvironment, leading to sustained malignancy. This multifactorial framework highlights both direct cellular insults and indirect systemic effects that act in synergy to promote carcinogenesis (Fig. 7). Henceforth, exposure to MPs/NPs should be recognized not only as an ecological and toxicological concern but also as a potential oncogenic risk factor. Future research must prioritize longitudinal studies and advanced models that can validate this mechanistic hypothesis across diverse tissues and exposure contexts, ultimately guiding risk assessment and preventive strategies.
Fig. 7Mechanistic Insights into Micro/Nanoplastic Exposure and Carcinogenesis. Microplastics and nanoplastics (MPs/NPs) enter the human body through ingestion, inhalation, and environmental exposure from food, water, air, and contaminated ecosystems. Upon cellular uptake, these particles trigger oxidative stress, dysbiosis, endotoxin release, and immune modulation, leading to chronic inflammation and epigenetic alterations. These interconnected processes provide mechanistic insights into how MPs/NPs may promote cancer initiation and progression