The presence of substantial quantities of plastic debris in the environment has been documented since the 1960s (1). However, it was not until 2004 that the term ‘microplastic’ (MP) was introduced in a report to characterize microscopic plastic debris (2), signifying the commencement of research focused on MPs. The production of plastic has surged markedly in recent decades. As of 2015, ~4.9 billion tons of plastic waste had accumulated in landfills or the natural environment. Projections indicate that this figure could rise to ~12 billion tons by 2050 (3). The nature of global MP pollution is of notable concern.

Compared with other suspended particulate matter, MPs are distinguished by their extensive size distribution, diverse shapes, low densities-often approximating that of water-and high persistence (4). Plastics that accumulate in substantial quantities in the environment undergo degradation due to several environmental factors, including ultraviolet radiation from sunlight, precipitation, water flow, biological oxidation and mechanical weathering. The degradation products exhibit a wide range of forms such as fragments, fibers, spheres, pellets, lines, sheets, flakes and foams, with fragments being the most prevalent (5). These products can be further classified by size into nanoplastics (NPs; ≤0.1 µm), MPs (≤5 mm), medium plastics (0.5–5 cm), megaplastics (5–50 cm) and macroplastics (≥50 cm) (6). The densities of plastics vary markedly, ranging from 50 kg/m³ for extruded polystyrene foam to 1,400 kg/m³ for polyvinyl chloride (PVC); however, the densities of numerous plastics are similar to that of water (4).

MPs can also be categorized into primary and secondary types based on their origin. Primary MPs are small plastic particles that are either intentionally manufactured or generated as by-products of industrial processes (7). They are commonly present in products such as exfoliating beads in facial cleansers (8). Secondary MPs originate from the fragmentation or degradation of larger plastic materials (9), with the majority of environmental MPs considered to be secondary in nature (10). Furthermore, the substantial persistence of MPs enables their prolonged presence in waste streams and environmental contexts. Research suggests that these particles can accumulate and persist in natural environments for decades (11). These characteristics notably influence their environmental mobility, distribution patterns, modes of human exposure and potential hazard levels.

A particularly concerning facet of pervasive MP pollution is their potential implications for human health. Research indicates that MPs can enter the human body via ingestion, inhalation or dermal contact, thereby posing diverse health risks (12). Among these, ingestion is identified as the predominant exposure pathway, with frequent vectors including marine crustaceans, fish (13), sea salt, lake salt (14), tap water, spring water and bottled water (15). Schwabl et al (16) reported the presence of MPs in human feces, indicating that following ingestion, MPs can traverse the esophagus, stomach, small intestine and large intestine. This pathway may lead to their accumulation in specific target organs, thus posing potential health risks. Research performed on mice and zebrafish has reported that ingested MPs can accumulate in the intestines, potentially causing intestinal damage or dysbiosis of the gut microbiota (17,18). Furthermore, prolonged accumulation of MPs may contribute to carcinogenesis (19). MPs are also present in atmospheric deposition as well as in both indoor and outdoor environments (20). These particles may originate from urban dust, synthetic textiles, material abrasion (such car tires or buildings) and the resuspension of surface MPs (21). Plastic particles measuring <5 µm in length and <3 µm in diameter are readily inhalable (22), with certain particles accumulating in lung tissue due to their inherent durability. This accumulation has the potential to contribute to pulmonary inflammation, fibrosis or cancer (23,24). Moreover, occupational exposure, particularly amongst workers in the textile or mining industries, has been associated with higher incidences of respiratory irritation (25). Previous studies have also highlighted dermal contact as a potential route for MPs to enter the body, with personal care products such as cosmetics, toothpaste and soaps being major sources (26,27). Wu et al (27) reported that the dermal barrier could be crossed by NPs (<100 nm), synthetic fibers (<25 µm), the monomers, as well as the additives due to the skin pores ranging from 40 to 8 µm. Furthermore, plastic particles may also gain entry through wounds, sweat glands or hair follicles (28).

In previous years, the relationship between MPs and tumorigenesis has emerged as a key focus in MP and human health research. Owing to their extensive surface area and high adsorption capacity, MPs serve as vectors for several environmental toxicants, including polycyclic aromatic hydrocarbons (29,30), heavy metals (31) and organochlorine pesticides (32), all of which are recognized as potent carcinogens. These substances can enter the human body alongside MPs and, under certain conditions, may be either released or retained, thus increasing the risk of carcinogenesis. Moreover, research indicates that MPs with diameters ranging from 0.25–10 µm can penetrate cell membranes and accumulate within cells, indicating their potential for prolonged persistence within the body (33,34). MPs may interact with cellular components through mechanisms (35–37) such as: i) Elevating intracellular reactive oxygen species (ROS) levels, which can lead to oxidative stress, lipid peroxidation, protein oxidation and DNA damage; ii) promoting cytokine release upon cellular contact, activating specific pathways and triggering inflammatory responses; and iii) disrupting immune surveillance by interacting with immune cells, activating innate immune receptors [such as toll-like receptors (TLR)] and perpetuating chronic inflammation. These mechanisms collectively create a conducive environment for tumor growth and influence the tumor microenvironment (TME).

The TME is a complex network consisting of tumor cells, several stromal cells (such as fibroblasts, lymphocytes, macrophages and endothelial cells) and extracellular components [such as cytokines, inflammatory cells, signaling molecules and extracellular matrix (ECM)] (38). It serves a crucial role in cancer development and progression. Recent in vitro experiments have demonstrated that exposure to polystyrene (PS)-NPs can promote the progression of ovarian cancer in murine models by modifying the TME (39), thereby providing further evidence of the connection between MPs and the TME.

Given that direct research on the TME in the context of MPs remains in its nascent stages, the present review aimed to analyze the interactions between MPs and the TME. By evaluating previous studies on the interactions of MPs with tumor cells, macrophages, fibroblasts, endothelial cells and inflammatory processes, the present study aimed to consolidate the latest evidence from research on both cancerous and normal tissue cells. Furthermore, the present study aimed to elucidate the potential links between MPs, the TME and tumorigenesis.

MPs can influence the TME by affecting several cell types. Fig. 1 illustrates a brief overview of the role of MPs in the TME.

Hanahan et al (73) proposed that inflammation notably contributes to the initiation and progression of tumors. Recognized as a hallmark of cancer, inflammation is implicated in every phase of tumorigenesis, encompassing development, malignancy, invasion and metastasis, whilst also interacting intricately with the TME. MPs intensify inflammatory responses by releasing cytokines, triggering inflammatory signaling pathways, inducing oxidative stress and establishing a microenvironment conducive to cancer initiation and progression (Table III) (37,74).

Inflammatory factors are critical in modulating inflammatory and immune responses and notably impact tumor progression within the TME through several mechanisms. These factors establish signaling pathways that mediate the pro-inflammatory effects of MPs and modify the microenvironment. Recent research has demonstrated that PS-NPs exacerbate lipopolysaccharide-induced duodenal inflammation in murine models via ROS-driven activation of NF-κB and NLRP3 (75). NF-κB is a pivotal regulator of pro-inflammatory mediator expression and serves a central role in the pathogenesis of inflammatory diseases. Notably, NF-κB operates in a cell-type-specific manner, facilitating the activation of genes that promote inflammation within the TME (76). The NLRP3 inflammasome contributes to the regulation of inflammatory responses by activating caspase-1, which in turn promotes the secretion of pro-inflammatory cytokines, IL-18 and IL-1β and induces pyroptosis (77). In vitro experiments have demonstrated that PS-MPs suppress cell viability via a mitochondria-dependent pathway, leading to increased production of ROS (78). Excessive ROS not only activates NF-κB but also serves as a critical mechanism for the activation of the NLRP3 inflammasome in response to exogenous stimuli (77,79,80). Consequently, the ROS-NF-κB-NLRP3 signaling pathway has emerged as a central focus in research concerning MPs and inflammation. Despite ethical considerations, a notable number of these experiments are performed using animal models. Wen et al (81) evaluated the relationship between exposure to PS-NPs and liver inflammation in mice, and reported that PS-NPs exposure markedly increased the expression levels of NLRP3, IL-1β and caspase-1, in addition to activating NF-κB. These results further corroborate the hypothesis that the ROS-NF-κB-NLRP3 signaling pathway is a mechanism through which PS-NPs induce inflammatory damage (81). Similarly, in a study by Zhang et al (82), the effects of varying concentrations of PS-MPs on chicken hearts and primary cardiomyocytes were assessed. The findings indicated that PS-MPs induced myocardial pyroptosis, inflammatory cell infiltration and mitochondrial damage via the NF-κB-NLRP3-gasdermin D signaling pathway. This process resulted in the upregulation of factors such as NLRP3, caspase-1, IL-1β, IL-18 and IL-6, thereby exacerbating myocardial inflammation (82). A comparable conclusion was drawn in a previous study evaluating the effects of PS-MPs on thymic inflammation in chickens (83). The study reported that PS-MPs induced oxidative stress in the thymus and activated the nuclear factor erythroid 2-related factor 2/NF-κB, Bcl-2/Bax and AKT signaling pathways. This activation subsequently enhanced the expression of downstream molecules such as IL-1β, caspase-3 and Beclin1, culminating in thymic inflammation, apoptosis and autophagy (83).

In addition to the ROS-NF-κB-NLRP3 signaling pathway, other studies have suggested that toll-like receptor 4 (TLR4), p38 and p50 may also serve a role in mediating the pro-inflammatory effects of MPs. Antunes et al (84) performed an experiment in which the human colorectal cancer HT29 cell line was exposed to PS-NPs. The results demonstrated that HT29 cells exhibited an upregulation of p50 and p38 expression, along with an increase in TLR4 expression. Notably, p38, a member of the MAPK family, is implicated in several signaling cascades, including those related to inflammatory responses, and is responsive to environmental stressors (85). TLR4 functions as a membrane protein in the pattern recognition receptor (PRR) family. The activation of TLR4 can lead to the synthesis of pro-inflammatory cytokines and chemokines (86), as well as the activation of the classical NF-κB pathway and p38, thereby promoting inflammatory responses (87). Consistent results were reported in a study by Woo et al (88), where exposure of mouse lungs and A549 cells to PP-NPs resulted in a marked increase in the number of inflammatory cells, ROS production and levels of inflammatory cytokines and chemokines both in vivo and in vitro. This was accompanied by elevated levels of phosphorylated p38 and NF-κB proteins. In A549 cells, the inflammation induced by PP exposure was regulated by inhibitors targeting p38 and ROS. These results suggest that PP-NPs can promote inflammation through p38-mediated NF-κB signaling pathways (88). Additionally, Danso et al (89) administered 5 mg/kg MP fragments intratracheally to mice over a period of 14 days to assess the pulmonary toxicity and inflammatory effects associated with MPs. Compared with the control group, the lung tissues of mice administered with PS-MP fragments exhibited an increased presence of inflammasome components, including NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain and caspase-1. This observation supports the conclusion that lung inflammation induced by PS microplastic fragments is mediated via TLR4 activation of the NF-ĸB and NLRP3 inflammasome pathways (89).

Although the pro-inflammatory pathways triggered by MPs in numerous experimental studies exhibit variability, they consistently implicate the NLRP3 inflammasome, underscoring its critical role in MP-induced inflammation. Contrarily, in the study by Han et al (90) on nano-sized MPs and their induction of inflammatory responses in skin cells, activation of the NLRP3 inflammasome was not detected. Instead, the study reported that nano-MPs upregulated the ‘absent in melanoma 2’ PRR in a concentration-dependent manner, thereby promoting the release of IL-1β and initiating the inflammatory response (90). This enhances the comprehension of inflammation induced by MPs.

On the other hand, beyond their pro-inflammatory effects, inflammatory factors have the potential to disrupt cellular junctions, alter the microenvironment and potentially contribute to malignant transformation. Zeng et al (91) reported that exposure of the human colorectal cancer Caco-2 cell line to PS-MPs resulted in increased permeability of tight junction proteins within the cultured Caco-2 monolayer. This effect is likely attributable to the induction of oxidative stress and the activation of NF-κB and the NLRP3 inflammasome by PS-MPs in Caco-2 cells, which subsequently elevated the expression of inflammatory factors, such as IL-6, IL-8, TNF-α and IL-1β (91). Notably, IL-1β is known to activate the NF-κB/myosin light chain kinase (MLCK) signaling pathway (92), whereas TNF-α stimulates IL-8 secretion, thereby promoting intestinal inflammation and MLCK expression (93). Consequently, PS-MPs elicit inflammatory responses and compromise colonic epithelial tight junctions through the ROS-dependent NF-κB/NLRP3/IL-1β/MLCK signaling pathway. This process enhances mucosal barrier permeability and perturbs the intestinal microenvironment (91).

MPs have become deeply embedded within human society, establishing themselves as a major global pollutant. Their persistence, mobility, high production volume and wide range of applications have led to their ubiquitous presence in the natural environment. Consequently, MPs are increasingly encountered by the human body, posing potential health risks and potentially elevating the likelihood of disease and cancer (94). Research has reported that under conditions characterized by high concentration, extended exposure and heightened individual susceptibility, MPs may exert cytotoxic effects through mechanisms such as chronic inflammation, oxidative stress, DNA damage, immunotoxicity and the delivery of toxic substances. It potentially culminates in malignant transformation (95). Furthermore, previous studies have broadened the scope of understanding regarding the effects of MPs, demonstrating their influence not only on tumor initiation but also on tumor progression by modulating the TME (39). Despite the nascent stage of research in this field and the limited scope of existing literature, the present review offers a systematic analysis of contemporary studies examining the interactions between MPs and several components of the TME. These elements include tumor cells, immune cells (with a focus on macrophages), endothelial cells, fibroblasts, ECM and inflammatory factors. The primary conclusion is that MPs within the TME markedly contribute to the proliferation and metastasis of tumor cells. They achieve this by modulating the immune cell status to enhance tumor activity, inducing structural changes in vascular endothelial cells, facilitating the activation of fibroblasts and the expression of associated proteins and directly influencing the ECM and inflammatory mediators. We hypothesize that these theoretical foundations will enhance the comprehension of the role of MPs in carcinogenesis and offer novel research trajectories for future scholars. Furthermore, they may identify new diagnostic and therapeutic targets for individuals whose health is compromised by MPs, including patients with cancer.

Similarly, carbon nanomaterials (CNMs) exhibit distinctive physical and chemical properties due to their nanoscale dimensions. CNMs present novel opportunities for cancer therapy by specifically targeting cancer cells and components of the TME (96). The present review serves as an impetus for the investigation into the application of MPs within the context of the TME. Nonetheless, the current understanding of the interaction between MPs and the TME represents merely the tip of the iceberg. Consequently, further research is imperative to elucidate the intricate relationship between MPs and cancer development, establishing it as a crucial area of study.

It is important to recognize that the present review revealed considerable variability in experimental outcomes, attributable to disparities in research methodologies, sample types, the physical properties of samples as well as exposure concentrations and durations. These inconsistencies present challenges in comparing and categorizing study findings. Therefore, future research on MPs and the TME should incorporate several MP types, concentrations and exposure durations, in both in vitro and in vivo settings, alongside rigorously designed control groups. Whilst this approach may increase the complexity of experiments, it will enhance the reliability and accuracy of the data and conclusions.

In summary, the study of MPs, tumors and the TME necessitates sustained research investment and the adoption of multidisciplinary methodologies. As the present review progressively unravels the complex web of interactions among these elements, the resulting insights will contribute to the development of more efficacious preventive measures, facilitate earlier detection and enhance therapeutic strategies for individuals affected by MPs.