The Cytotoxicity of Biodegradable Microplastics and Nanoplastics: Current Status and Research Prospects

Abstract

The growth in the production and use of biodegradable plastics, positioned as an environmentally friendly alternative to traditional polymers, has led to an increase in their distribution in the environment. However, in conditions other than industrial composting facilities, biodegradable polymers can persist for a long time, fragment, and form biodegradable micro- and nanoplastics (BioMNP) with potential toxicity. Unlike traditional microplastics, the impact of BioMNP on human health has been poorly studied. This review summarises the available data on the cytotoxicity of BioMNP, including mechanisms of interaction with human cells, routes of entry into the body, induction of inflammation, oxidative stress, and cellular dysfunction. Particular attention is paid to the interaction of microplastics with cells of various body systems, including the digestive, respiratory, immune, and urogenital systems, as well as with the skin. The identified knowledge gaps highlight the need for further research to assess the risks associated with the impact of BioMNP on humans and to develop safer forms of biopolymers. Among biodegradable plastics, PLA-based particles tend to exhibit stronger cytotoxic effects. Nanoplastics generally induce more severe cellular responses than microplastics. Organs such as the liver and lungs appear particularly vulnerable.

1. Introduction

The widespread use of polymers in all areas of life has given a significant boost to industrial development, but at the same time, it has created the problem of plastic waste disposal. Although various plastic recycling technologies have long been implemented industrially, challenges remain in terms of collection efficiency and material quality. Therefore, millions of tonnes of polymers are polluting the land and water. Under the influence of the environment, pieces of plastic break down into smaller particles, forming microplastics (MP). Microplastics are considered to be particles ranging in size from 1 μm to 5 mm [1]. The situation with nanoplastics is a little more complicated, as there is still debate about what exactly constitutes nanoplastics [2]. In this article, nanoplastics will be defined as particles smaller than 1 μm. Micro- and nanoplastics pollution has become a serious environmental problem, and studies confirm its presence in water, soil, and human tissues [3,4]. Initially, biodegradable plastics were considered an environmentally friendly alternative that could solve the problem of environmental pollution [5]. The potential toxicity of biodegradable plastics is due to their persistence in the environment; the authors report that the rate of decomposition of a PHA bottle in water can take up to 3.5 years [6]. Other bioplastics also tend to decompose very slowly, which contributes to the release of bioadditives and the formation of biodegradable micro- and nanoplastics (BioMNPs) with reactive surfaces and degradation byproducts [7,8]. They decompose into H₂O and CO₂ only in compostable conditions, and when they enter the environment, their degradation rate and environmental persistence resemble those of conventional plastics [9]. Under natural conditions, the biodegradation of biopolymers is influenced by many chemical, physical, and biological factors, as a result of which their decomposition rate and nature of degradation can vary significantly, leading to their long-term preservation in the environment, weathering of additives, and the formation of biodegradable micro- and nanoplastics [10]. Like conventional microplastics, BioMPs may act as carriers of microorganisms and heavy metals [11,12]. This may also impact their toxicity, but no articles have been found that assess the toxicity of BioMPs in combination with heavy metals and human cells. Most studies focus on the impact of contaminated particles on the rhizosphere.

Currently, the review articles found on the toxicity of BioMNP are mainly devoted to plants and model animals [13,14,15]. Reviews devoted to cytotoxicity to humans are mainly related to microplastics made from petroleum-based polymers [16,17,18]. As a rule, MPs cause cytotoxicity, such as oxidative stress, damage to cell membranes and organelles, activation of the immune response, and genotoxicity, through mechanical damage or induction of cells to produce reactive oxygen species. In addition, all these reviews concur that there is currently limited data on this topic, and that further testing and standard procedures need to be developed in the field of microplastic toxicity.

This review explores the potential cytotoxic effects of BioMNPs, which, like conventional MPs, may enter the human body through inhalation or the consumption of water or food [19,20]. The growing adoption of biodegradable packaging is expected to increase human exposure to BioMNPs through ingestion and inhalation [21]. By 2029, the production of biodegradable bioplastics will grow threefold to 3.7 million tonnes [22].Therefore, assessing the potential health risks associated with such exposure is critical for regulators and material developers.

This review provides a comprehensive synthesis of current in vitro and in vivo findings on the cytotoxicity of BioMNPs, structured by organ systems, and highlights key knowledge gaps requiring further investigation. Given the growing use of biodegradable plastics in consumer products, a comprehensive evaluation of their cytotoxicity is essential to inform regulatory decisions and guide safer material design.

2. Methods: Literature Search Strategy

At the time of writing this review (July 2025), 17 scientific articles devoted to the study of the interaction between biodegradable plastic particles and living cells were found in the Scopus and Web of Science databases. The research methodology included a search of the Scopus and Web of Science databases using the query ‘cytotoxicity of biodegradable microplastics.’ For greater detail, specific organs or cells (‘intestine’, ‘lungs’, and ‘Caco-2’) from the articles found were added to the query. Specific polymers, such as ‘PLA’, ‘PBS’, ‘PBAT’, etc., were also added. To ensure comprehensive coverage, the search query also included the following terms: (biodegradable OR bio-based) AND (microplastics OR nanoplastics) AND (cytotoxicity OR cell viability OR toxicity). Since this field of science is still relatively young, no specific timeframe has been established for the selection of articles. The criterion for inclusion in the review was the availability of results specifically related to the effect of bioplastics on the cells themselves. The exclusion criteria were as follows: research on non-biodegradable microplastic particles and the absence of an English version of the text. Comments, summaries, reviews, editorial articles, and duplicate studies were also excluded. A brief infographic with detailed information about the materials used, cells, and sizes of BioMNP is presented in Section 3.

3. Cytotoxicity of Biodegradable Micro- and Nanoplastics

The articles found examined a wide range of biodegradable polymers. The characteristics of bioplastics (including the nature of the biopolymer and particle size) is presented in Figure 1, and a summary of the main results is provided in Table 1. The most frequently tested materials are PLA, PBAT, and PBS, which is logical since these polymers are the most used in biodegradable packaging.

There are also publications with research on PHA, PHB, and PBC. Depending on the rate of degradation of materials and their decomposition products, they may have different cytotoxicity.

In studying the cytotoxicity of biomaterials, researchers try to cover as wide a range of particle sizes as possible (Figure 1). Particles up to 100 micrometres account for a significant portion of the research since it is the smaller particles that can penetrate biological barriers (intestines, lungs). Their high surface area-to-volume ratio makes them more reactive. Micro-sized particles constitute the bulk of BioMP. Macrophages can absorb smaller particles up to 10 μm, while larger particles interact more with tissues. Researchers often use particles with polydispersity in size, which allows for a more realistic picture of the interaction between cells and microplastics.

Analysing Table 1, it is worth noting the wide range of concentrations used in in vitro tests for BioMP cytotoxicity. When converted to a single format, the values range from 0.00078125 μg/mL to 1000 μg/mL. Serial dilutions are also used, most often twofold, as in articles [23,24,25], which is typical for cytotoxicity tests when searching for hazardous concentrations. This can also aid in the development of standards that regulate the absence of cytotoxicity at specific concentrations. It is also worth noting the variability of concentrations: most often, the mass-to-volume ratio is used, but there are also concentrations of microplastic particles per well (for large particle sizes), mass-to-area when studying the interaction of nanoplastics and a lung barrier model, and volume-to-volume when studying the effect of substances released from particles on cells [26].

The articles investigated the interaction of BioMPs with a wide range of cells, encompassing various biological contexts (Figure 2). Some researchers focus on modelling the pathways of exposure to different body systems. The digestive system was simulated using Caco-2, HT29 (intestinal epithelium), HepG2, L-02 (liver cells), and STC1 (stomach cells) cells. A549 and Calu-3 lung epithelial cells were used to assess the risk of inhaling BioMNP. HaCaT and NHDF cells were used to simulate skin contact. When particles enter the bloodstream, the reaction can be assessed using HUVEC vascular endothelial cells. In several studies, the authors used RAW 264.7, THP-1, and ImKC macrophage cell lines. This enables the assessment of inflammatory reactions in cells, which is the primary mechanism of toxicity for many materials. One study compared the effect on normal and cancerous liver cells, L-02 and HepG2, which are the standards for toxicology. Researchers also assess the impact on the gut microbiota.

Table 1. Summary of reviewed studies on the impacts of BioMNP on cells and animals.

Materials	Size	Concentration	Cells/Animals	Results	Reference
Commercial products based on PLA and PHB	100 nm–10 µm	0.78125, 1.5625, 3.125, 6.25, 12.5, 25, 50, and 100 µg/L	A549 HepG2	Plastic particles and their extracts did not reduce cell viability but induced oxidative stress, most notably with PLA.	[23]
PLA PBS	4.41 µm 7.64 µm	6.25, 12.5, 25, 50, and 100 µg/mL	Vero NHDF HaCaT	Microplastic particles had substantially less toxic to practically non-toxic effects on the cells. Plastics potentially have more alteration effect in epithelial kidney cells (Vero) than fibroblasts (NHDF) and keratinocytes (HaCaT) Microplastic particles were non-toxic or harmless to animal cell lines and altered some intracellular biomolecule profiles.	[24]
PLA	160 nm	50, 100 µg/ml	Caco-2 HT29	PLA-NPLs (≤100 μg/mL, 48 h) caused no cytotoxicity or barrier disruption in Caco-2/HT29 cells. A slight, temporary TEER drop occurred at 3 h. Uptake was high, especially in HT29, with retention up to 72 h.	[25]
PLA	130 nm	2.5, 10, and 20 µg/cm2	Calu-3	PLA-NPLs were internalised by 10–70% of Calu-3 cells (dose- and time-dependent), localising near and inside nuclei. Exposure (2.5 µg/cm2) reduced ZO-1 expression and slightly increased mucus secretion. Genotoxicity increased with exposure time (~7% DNA damage at 2 weeks); not linked to oxidative stress. Prolonged exposure triggered strong inflammatory responses, altering expression of up to 20 cytokines and related proteins.	[26]
PGA PBSG	50 µm	50 and 500 mg/kg	Wistar rats	High doses of all three polyesters resulted in decreased body weight, tissue necrosis, and inflammation in rats. PGA, having the fastest degradation rate, showed the least physiologic toxicity. Low doses of biodegradable plastics did not cause significant toxicity	[27]
PLA	25 μm	0.0008, 0.004, 0.02, 0.1, and 0.5 mg/ml	HepG2 Caco-2 HUVEC RAW 264.7	In vitro, PLA nanoparticles and oligomers penetrated HepG2, Caco-2, and HUVEC cells, with higher uptake of oligomers. In vivo, orally administered PLA oligomers and degradation products accumulated in the liver, intestine, and brain. Both PLA MPs (even at 0.01 mg/day) and oligomers induced acute liver and intestinal inflammation and impaired the intestinal barrier, with stronger effects from oligomers.	[28]
Polymer MP PLA (~40 kDa) Oligomer MP PLA (~2 kDa)	~2.5 μm	2.5 or 25 mg/kg	in vivo 28-day oral administration to mice	Particles from both groups were found in major organs, with polymeric MP accumulating more in the brain, liver, spleen, and lungs, and oligomeric MP—in blood and kidneys. Oligomeric MP also showed higher intestinal accumulation. Nanoparticles crossed the blood-brain barrier without disrupting its integrity. Both PLA MP forms (2.5 and 25 mg/kg/day, 28 days) induced Parkinson-like neurotoxicity, with polymeric MP causing stronger effects.	[29]
PLA	1–1000 nm	-	Phospholipid bilayers	Nanoplastic–lipid bilayer interaction was mainly driven by van der Waals forces, strongest for PLA and weakest for PP. All nanoplastics increased bilayer surface roughness and decreased its thickness. These changes may impair membrane function and cause cytotoxicity, including hemolysis.	[30]
PLA	1–4 µm	20 particles on cell	ImKC (Kupffer cells) J774A.1 STC1 BNL CL.2	Microplastic particles showed no significant short-term cytotoxicity against macrophages and epithelial cells.	[31]
PGA PLA PBS, aged PBS PBC PBAT	~800 nm	1, 25, 100 mg/L	LO2 THP-1 HUVEC Caco-2	PLA and PBS showed significant toxicity to human cell lines, while PGA had low cytotoxicity and little antiproliferative effect. THP-1 cells internalized PGA microplastics. Aging reduced PGA toxicity, particularly in HUVEC.	[32]
PBAT	Extracts from films		L-02	Decreased cell viability and increased liver damage markers (AST, ALT). Oxidative stress indicated by higher ROS and lower SOD, GSH levels. Inflammation with elevated TNF-α, IL-6, and IL-1β. Reduced ATP levels. Altered AMPK signalling: increased p-AMPK/AMPK ratio and decreased p-mTOR/mTOR, SIRT1, PGC-1α, NRF1, and TFAM.	[33]
PLA	1mm 240 ± 65 µm	0.166 g	Gut microbiota	PLA MPs did not significantly disrupt microbial community homeostasis, with bifidobacteria levels tending to increase. Functional shifts suggest altered microbial metabolism and possible PLA biotransformation by colon microbiota. Raman spectroscopy and FESEM showed PLA MPs’ morphological changes after gastric digestion and surface biodegradation with microbial biofilm after intestinal and colonic phases.	[34]
PBS PBS+0.1% Cellulose nanocrystals	125–140 µm	0, 10, 100, 500 and 1000 µg/mL	MDA-MB-231 CHO-K1 KB RAW 264.7	Incubation of CHO-K1 cells with agar-fixed particles (up to 1000 μg/mL, 72 h) caused no significant cell death. Direct exposure to KRICT-PBS and CNC-PBS particles (up to 1000 μg/mL) for 72 h had minimal effect on viability of MDA-MB-231, CHO-K1, KB, and RAW 264.7 cells.	[35]
PLA	600–850 µm	3 and 8 particles per well	Mouse macrophages of the RAW264.7	Low microplastic dose (3 particles/well) had no effect on cell viability. High dose (8 particles/well) treated at 120–130 °C slightly increased viability, while treatment at 140 °C significantly reduced it (~83.9%).	[36]
Aged PLA/PBAT	5 mm 863 nm 608 nm	0, 0.1, 1, 10, 100, 200, 500, and 1000 mg/L	THP-1	UV aging of PLA/PBAT films increased surface roughness and triggered MNP release. These MNPs reduced THP-1 cell viability dose-dependently, with ultrafiltration-derived MNPs showing higher toxicity. PLA/PBAT MNPs posed toxicity risks equal to or greater than conventional plastic MNPs.	[37]
PLA	211.78 nm	from 6.25 to 200 µg/mL	Bhas 42	It did not show the ability to transform cells under either initiation or promotion conditions. Nanoplastics effectively penetrated inside the cells Bhas 42	[38]
PBAT PBAT+1.5%CB+1,5% HALS PBAT+1.5%CB+1,5% VitE	Aqueous extract of soil	100, 250, 500, 750 and 1000 µL/mL	HepG2/C3A	MTT assay showed decreased HepG2/C3A viability with higher aqueous soil extract concentrations, but viability remained above 80% at 250 μL/mL. Micronucleus test revealed no cytotoxicity at this concentration (CBPI comparable to control). No genotoxic effects were detected in soil extracts with films before or after photo- and biodegradation (Tail DNA % and Olive tail moment unchanged).	[39]

Table 1. Summary of reviewed studies on the impacts of BioMNP on cells and animals.

Materials	Size	Concentration	Cells/Animals	Results	Reference
Commercial products based on PLA and PHB	100 nm–10 µm	0.78125, 1.5625, 3.125, 6.25, 12.5, 25, 50, and 100 µg/L	A549 HepG2	Plastic particles and their extracts did not reduce cell viability but induced oxidative stress, most notably with PLA.	[23]
PLA PBS	4.41 µm 7.64 µm	6.25, 12.5, 25, 50, and 100 µg/mL	Vero NHDF HaCaT	Microplastic particles had substantially less toxic to practically non-toxic effects on the cells. Plastics potentially have more alteration effect in epithelial kidney cells (Vero) than fibroblasts (NHDF) and keratinocytes (HaCaT) Microplastic particles were non-toxic or harmless to animal cell lines and altered some intracellular biomolecule profiles.	[24]
PLA	160 nm	50, 100 µg/ml	Caco-2 HT29	PLA-NPLs (≤100 μg/mL, 48 h) caused no cytotoxicity or barrier disruption in Caco-2/HT29 cells. A slight, temporary TEER drop occurred at 3 h. Uptake was high, especially in HT29, with retention up to 72 h.	[25]
PLA	130 nm	2.5, 10, and 20 µg/cm2	Calu-3	PLA-NPLs were internalised by 10–70% of Calu-3 cells (dose- and time-dependent), localising near and inside nuclei. Exposure (2.5 µg/cm2) reduced ZO-1 expression and slightly increased mucus secretion. Genotoxicity increased with exposure time (~7% DNA damage at 2 weeks); not linked to oxidative stress. Prolonged exposure triggered strong inflammatory responses, altering expression of up to 20 cytokines and related proteins.	[26]
PGA PBSG	50 µm	50 and 500 mg/kg	Wistar rats	High doses of all three polyesters resulted in decreased body weight, tissue necrosis, and inflammation in rats. PGA, having the fastest degradation rate, showed the least physiologic toxicity. Low doses of biodegradable plastics did not cause significant toxicity	[27]
PLA	25 μm	0.0008, 0.004, 0.02, 0.1, and 0.5 mg/ml	HepG2 Caco-2 HUVEC RAW 264.7	In vitro, PLA nanoparticles and oligomers penetrated HepG2, Caco-2, and HUVEC cells, with higher uptake of oligomers. In vivo, orally administered PLA oligomers and degradation products accumulated in the liver, intestine, and brain. Both PLA MPs (even at 0.01 mg/day) and oligomers induced acute liver and intestinal inflammation and impaired the intestinal barrier, with stronger effects from oligomers.	[28]
Polymer MP PLA (~40 kDa) Oligomer MP PLA (~2 kDa)	~2.5 μm	2.5 or 25 mg/kg	in vivo 28-day oral administration to mice	Particles from both groups were found in major organs, with polymeric MP accumulating more in the brain, liver, spleen, and lungs, and oligomeric MP—in blood and kidneys. Oligomeric MP also showed higher intestinal accumulation. Nanoparticles crossed the blood-brain barrier without disrupting its integrity. Both PLA MP forms (2.5 and 25 mg/kg/day, 28 days) induced Parkinson-like neurotoxicity, with polymeric MP causing stronger effects.	[29]
PLA	1–1000 nm	-	Phospholipid bilayers	Nanoplastic–lipid bilayer interaction was mainly driven by van der Waals forces, strongest for PLA and weakest for PP. All nanoplastics increased bilayer surface roughness and decreased its thickness. These changes may impair membrane function and cause cytotoxicity, including hemolysis.	[30]
PLA	1–4 µm	20 particles on cell	ImKC (Kupffer cells) J774A.1 STC1 BNL CL.2	Microplastic particles showed no significant short-term cytotoxicity against macrophages and epithelial cells.	[31]
PGA PLA PBS, aged PBS PBC PBAT	~800 nm	1, 25, 100 mg/L	LO2 THP-1 HUVEC Caco-2	PLA and PBS showed significant toxicity to human cell lines, while PGA had low cytotoxicity and little antiproliferative effect. THP-1 cells internalized PGA microplastics. Aging reduced PGA toxicity, particularly in HUVEC.	[32]
PBAT	Extracts from films		L-02	Decreased cell viability and increased liver damage markers (AST, ALT). Oxidative stress indicated by higher ROS and lower SOD, GSH levels. Inflammation with elevated TNF-α, IL-6, and IL-1β. Reduced ATP levels. Altered AMPK signalling: increased p-AMPK/AMPK ratio and decreased p-mTOR/mTOR, SIRT1, PGC-1α, NRF1, and TFAM.	[33]
PLA	1mm 240 ± 65 µm	0.166 g	Gut microbiota	PLA MPs did not significantly disrupt microbial community homeostasis, with bifidobacteria levels tending to increase. Functional shifts suggest altered microbial metabolism and possible PLA biotransformation by colon microbiota. Raman spectroscopy and FESEM showed PLA MPs’ morphological changes after gastric digestion and surface biodegradation with microbial biofilm after intestinal and colonic phases.	[34]
PBS PBS+0.1% Cellulose nanocrystals	125–140 µm	0, 10, 100, 500 and 1000 µg/mL	MDA-MB-231 CHO-K1 KB RAW 264.7	Incubation of CHO-K1 cells with agar-fixed particles (up to 1000 μg/mL, 72 h) caused no significant cell death. Direct exposure to KRICT-PBS and CNC-PBS particles (up to 1000 μg/mL) for 72 h had minimal effect on viability of MDA-MB-231, CHO-K1, KB, and RAW 264.7 cells.	[35]
PLA	600–850 µm	3 and 8 particles per well	Mouse macrophages of the RAW264.7	Low microplastic dose (3 particles/well) had no effect on cell viability. High dose (8 particles/well) treated at 120–130 °C slightly increased viability, while treatment at 140 °C significantly reduced it (~83.9%).	[36]
Aged PLA/PBAT	5 mm 863 nm 608 nm	0, 0.1, 1, 10, 100, 200, 500, and 1000 mg/L	THP-1	UV aging of PLA/PBAT films increased surface roughness and triggered MNP release. These MNPs reduced THP-1 cell viability dose-dependently, with ultrafiltration-derived MNPs showing higher toxicity. PLA/PBAT MNPs posed toxicity risks equal to or greater than conventional plastic MNPs.	[37]
PLA	211.78 nm	from 6.25 to 200 µg/mL	Bhas 42	It did not show the ability to transform cells under either initiation or promotion conditions. Nanoplastics effectively penetrated inside the cells Bhas 42	[38]
PBAT PBAT+1.5%CB+1,5% HALS PBAT+1.5%CB+1,5% VitE	Aqueous extract of soil	100, 250, 500, 750 and 1000 µL/mL	HepG2/C3A	MTT assay showed decreased HepG2/C3A viability with higher aqueous soil extract concentrations, but viability remained above 80% at 250 μL/mL. Micronucleus test revealed no cytotoxicity at this concentration (CBPI comparable to control). No genotoxic effects were detected in soil extracts with films before or after photo- and biodegradation (Tail DNA % and Olive tail moment unchanged).	[39]

3.1. Organism

First and foremost, it is interesting to know how microplastic particles are distributed within the body when they enter. Several studies have examined the effects of micro- and nanoplastics administered orally to rats and mice. Zhang et al. used biodegradable poly(glycolic acid) (PGA) and its copolymer, poly(butylene succinate-co-glycolate) (PBSG), with an average size of approximately 50 micrometres in their work [27]. The particles were administered orally to rats at two doses: low (50 mg/kg body weight) and high (500 mg/kg body weight), administered every 24 h for 7 days. PGA and PBSG degraded significantly in the digestive tract.

Of the 700 mg administered, 290 mg of PGA and 425.3 mg of PBSG were recovered, meaning that 41.4% of PGA and 60.7% of PBSG were excreted, while the remainder (410 mg of PGA and 175 mg of PBSG) remained in the body in the form of low-molecular-weight fragments. When comparing these two materials, PGA proved to be less toxic as indicated by higher cell viability and lower expression of inflammatory markers. The authors suggest that this is due to its faster degradation rate. At low doses, it caused minimal organ damage and only slight liver damage, while at high doses, it led to a significant reduction in liver and stomach weight, as well as slight kidney damage. Damage to kidney tissue was more pronounced due to the excretion of acetic acid formed during the decomposition of PGA. Another polymer, PBSG, caused a significant reduction in liver and stomach weight at high doses, as well as a slight decrease in kidney weight. At high doses, it also led to liver dysfunction and inflammation. At low doses, mild inflammation was observed in the kidney area. The author expresses grave concern about the possible toxicity of BioMPs.

In another study, Wang et al. investigated the effects of realistic doses of microplastics and PLA-based oligomers [28]. The microplastics were approximately 25 μm in size, and the oligomers had a molecular weight of approximately 900 Da. All forms were labelled with fluorescein (FITC) for tracking in tissues. Mice were given 1 mg per day of PLA MPs or PLA oligomers orally for 7 days. As a result, it was noted that PLA microparticles fragmented in the intestine; the particles accumulated in the liver, intestines, and brain. Acute inflammation was also observed in the liver, small intestine, and large intestine. Oligomers with lower molecular weight showed stronger toxicity in some cell lines, potentially due to higher solubility and increased cellular uptake under specific experimental conditions. The authors describe a possible mechanism of inflammation. It is associated with inactivation by matrix metallopeptidase 12 (MMP12). PLA oligomers have a high affinity for binding to the catalytic zinc-ion domain, resulting in the inactivation of MMP12. MMP12 may modulate inflammatory responses and has been suggested to influence components of the complement system, though direct inactivation remains to be conclusively demonstrated. Thus, PLA toxicity is most likely associated with oligomers that are released during PLA degradation in the intestine.

The study by Liang et al. also investigated the effect of PLA microparticles and oligomers on mice [29]. Both types of particles were labelled with fluorescent markers and had a size of 2.5 μm. The molecular weight differed between 40 kDa and 2 kDa for microparticles and oligomers, respectively. The mice were fed for 28 days via a gastric tube at doses of 2.5 and 25 mg/kg. As a result, both types of particles were distributed throughout the mice’s bodies and were found in the blood, brain, liver, spleen, lungs, kidneys, and testicular appendages (Figure 3). The particles were absent only in the heart and testicles. Particles from PLA MP polymers showed higher distribution in the cortex, striatum, and midbrain. Oligomeric particles, on the other hand, showed a preference for the hippocampus and cerebellum. Once in the brain, the particles caused neurotoxicity similar to Parkinson’s disease. A possible mechanism for neurotoxicity is the overexpression of MICU3, which leads to mitochondrial calcium overload and subsequent cell death. One way to reduce toxicity was to use an MCU inhibitor (MCU-i4) or a calcium exchange activator (DBcAMP). In the study by Wang et al. [28], compared to polymers, the oligomers appeared less toxic and did not induce ROS production, indicating that their effects may depend on different mechanisms or exposure routes. PLA oligomers were broken down more quickly into safe monomers, while polymer particles degraded more slowly and unsteadily during digestion and formed more nanoparticles.

Although direct evidence of human health risks is limited, these pathological studies in rodents raise serious concerns. Future research should focus on elucidating the mechanisms linking degradation rate and molecular weight to biotoxicity. Additionally, understanding the long-term impact of these relationships on human health will be crucial for establishing regulatory standards and promoting safer, biodegradable options.

The article will further examine the interaction of micro- and nanoplastics derived from biodegradable polymers with tissue cells from various organs.

3.2. Interaction Between NP and Membrane

Based on molecular dynamics simulations, Yuan et al. proposed a potential endocytosis mechanism of interaction between nanoplastic particles and a model bisphospholipid membrane [30]. For PVC and PP nanoplastics, the primary mechanism was endocytosis (absorption). However, for PLA nanoplastics, a different mechanism was observed, namely adhesion to the phospholipid layer. The level of bilayer wrapping was reported to remain low. To penetrate the bilayer, particles must overcome a free energy barrier of 4–22 kcal·mol⁻¹, which complicates further endocytosis. The authors also argue that the interaction between particles and the lipid bilayer is determined by Van der Waals forces rather than electrostatic interaction. Nanoplastics also tend to be pushed out of the aqueous phase towards the interface region.

3.3. Lungs

One way micro- and nanoplastics spread is through air currents, which carry them long distances via wind, snow, sea spray, and fog [40,41]. Every year, between 0.013 and 25 million tonnes of MNPL are transported by these means, with such a wide range due to a lack of data [42]. Thus, due to the presence of MNP particles in the air, inhalation becomes one of the main routes of exposure to humans. Microplastic particles have been found in all areas of the human lung, confirming possible concerns in this regard [43]. In this regard, it is necessary to investigate the interaction of lung cells with biodegradable micro- and nanoplastics.

In a study by García-Rodríguez et al., the interaction of PLA-based nanoplastics with the Calu-3 in vitro model of bronchial epithelium was investigated [26]. The particle size was approximately 130 nm. The model used was in air–liquid interface (ALI) conditions, which accurately mimic the physiological conditions of the lungs, including tight junctions and mucus secretion. Since this was a tissue simulation, the concentration was calculated as mass per area and ranged from 2.5 to 20 µg/cm². Firstly, particle internalisation into cells was observed, which depended on the concentration. After 24 h, at the minimum concentration, 10% of cells were internalised, and at the maximum concentration, 70% were internalised. With prolonged exposure (2 weeks) at a concentration of 2.5 µg/cm², internalisation reached 35% (Figure 4A). The authors also demonstrated that internalised particles could interact with the nuclear membrane and even penetrate inside. This was the reason for the genotoxicity of the particles, especially during prolonged exposure. DNA damage was attributed primarily to direct particle–cell interactions rather than oxidative mechanisms [44]. In addition to genotoxicity, an effect on ZO-1, a protein that plays a key role in the formation of tight contacts between cells, was also identified [45]. After two weeks of the experiment, the intensity of ZO-1 staining decreased by 50%, indicating changes in the entire structure of the barrier.

In another study using A549 lung cells, PHB and PLA particles obtained from commercial products were investigated [23]. The particle size ranged from 100 nm to 10 µm. In addition to studying the interaction of MNP particles, the authors also examined the amount of additives contained in commercial products. On average, PLA and PHB products contain about 120 plastic additives, including plasticisers and intermediate reaction products, solvents, and cross-linkers. The PHB and PLA particles themselves, of which there were eight different types, did not cause a decrease in cell viability. At the same time, the authors showed that PLA particles cause greater oxidative stress compared to PHB particles (Figure 4B). It is difficult to determine precisely what causes this, whether it is the inherent nature of the polymers themselves or the presence of additives in commercial mixtures. One PLA sample, which caused the ROS effect at a minimum concentration of 1 µg/L, contained the highest concentrations of additives. In addition, this sample was found to contain 4-sec-butyl-2,6-ditert-butylphenol in concentrations above 2800 ng/g, a compound classified by the European Chemicals Agency (ECHA) as irritating and hazardous to the environment (Figure 4C) [23].

Currently, available data are insufficient to draw definitive conclusions regarding of the effect of micro- and nanoplastics on human lung epithelium. The maximum observation period is 14 days, whereas in real life, the interaction is more chronic and longer tests are necessary. García-Rodríguez et al. put forward two assumptions regarding the lung epithelium: (i) human epithelium can clearly modulate/regulate the temporary absorption and passage of various particles (i.e., polymer type, size, and surface functionalisation) depending on the origin of the epithelium or cell type function; and (ii) the epithelium actively works to maintain tissue homeostasis. Overall, Calu-3 bronchial epithelium in vitro demonstrates remarkable plasticity and endurance under prolonged exposure to PLA NP [26].

3.4. Digestion

In addition to inhalation, micro- and nanoplastics can enter the body through water and food, where they interact with cells in the digestive system [46,47]. Every day, an adult consumes about 300 microplastic particles, some of which may be biodegradable [48].

In their article, Banaei et al. investigated the interaction of PLA nanoparticles released from tea bags with cell cultures isolated from colon adenocarcinoma [25]. Caco-2 and HT29 were used as (i) undifferentiated monocultures and (ii) differentiated cultures for the cell barrier model. The size of the particles studied was 114 nm, and the concentrations studied were 0, 50, and 100 μg/mL. As a result, after exposure to 100 μg/mL PLA-NPLs for 48 h, no significant cytotoxicity was observed in the monocultures of undifferentiated Caco-2 and HT29 cells and the Caco-2/HT29 intestinal barrier. The only negative result was a statistically significant decrease in barrier integrity (TEER value), which, however, disappeared after 24 h. This study demonstrated that PLA nanoparticles can penetrate the cell barrier, as observed in the lungs, while also showing the relative non-toxicity of PLA MNPs in a single interaction (Figure 5). Also, this study did not assess genotoxicity. This raises the question of future studies of repeated and chronic interaction of PLA MNPs with Caco-2 and HT29 cells. The penetration of nanoplastics into Caco-2 cells was also shown in the article by Wang et al. [28]. Nanoparticles and oligomers from PLA obtained during simulated digestion of microplastic particles from PLA were 50 nm and 900 kDa in size, respectively. The resulting particles showed high internalisation into Caco-2 and HepG2 cells.

In another article, which investigated PLA microparticles approximately 2 μm in size and BNL CL.2 cells (epithelial-type hepatocytes) and STC-1 cells (intestinal epithelial cells), virtually no cytotoxicity was demonstrated [31]. Both cell types did not absorb PLA particles at all, but STC-1 cells do not have a mechanism for absorbing particles of this size, while BNL CL.2 cells do. Metabolic activity, assessed using the MTT test, remained unchanged for STC-1 cells, whereas for BNL CL.2 cells, it decreased at the highest concentration but still remained above 80%. No changes in ROS formation were observed either. It can be assumed that all these effects are related to the lack of PLA uptake by these cells.

Cytotoxicity can be caused not only by the particles themselves but also by the additives they contain. Earlier, the cytotoxicity of PLA microplastics obtained from disposable products containing commercial additives [23] was demonstrated with human A549 lung cells. The same article also investigated the cytotoxicity of extracts from plastic additives made from the same materials on human HepG2 hepatocyte cells. Extracts of bioplastics (PLA, PHB) showed a maximum reduction in HepG2 cell viability of 15%, which was not statistically significant. Plastic additive extracts caused oxidative stress in HepG2 cells, with PLA extracts showing the most significant effect. Thus, it can be assumed that even in the absence of particle absorption by cells, they can release toxic substances and affect cell viability.

Digestive system cells were discussed in the publication by Wen et al. [32]. A wide range of nanoscale particles (~800 nm) made of PGA, PLA, PBS, PBC, and PBAT were studied in interaction with normal human liver cells (LO2) and human colon carcinoma cells (Caco-2). The results showed that all five materials had an antiproliferative effect on LO2, but among the tested materials, PLA showed the highest in vitro toxicity under the described conditions. It is worth noting that the authors did not observe such an effect in Caco-2 cells. The authors suggest that this is due to enzymes secreted by Caco-2, which can neutralise the decomposition products of the particles. PGA and aged PGA also stimulated the proliferation of Caco-2 cells, which is consistent with the frequent use of PGA in medical devices [49,50]. Due to its short decomposition time and low plasticity, PGA is practically not used in packaging materials in its pure form [51]. Therefore, the risk of microplastic formation and its entry into the human body is minimal. Further research into the cytotoxicity of biodegradable plastics has been strongly recommended.

In addition to PLA, PBAT is also frequently used in packaging. In their article, Chen et al. examined extracts from PBAT films with modified starch and their effect on LO2 hepatocytes [33]. It was demonstrated that the compounds in the extracts affected the viability of LO2 cells, and an increase in AST (aspartate aminotransferase), ALT (alanine aminotransferase), TNF-α, IL-6, and IL-1β (markers of inflammation), as well as ROS (reactive oxygen species), was also observed. There was a decrease in SOD (superoxide dismutase), GSH (glutathione), and ATP (adenosine triphosphate). Changes were also observed in the AMPK signalling pathway. Thus, compounds migrating from mixed films of modified starch with PBAT, upon contact with food, can cause oxidative stress and inflammation in hepatocytes, as well as damage hepatocytes through the AMPK pathway.

In addition to packaging, PBAT is also used in mulching films. Souza et al. investigated the toxicity of soil extracts after PBAT degradation in soil [39]. At the maximum concentration tested (250 μL/mL), the viability of HepG2/C3A cells exceeded 80%, indicating no cytotoxicity. The comet assay also showed no genotoxic effects, as did the micronucleus assay. Thus, the authors state that aqueous extracts prepared from the soil with PBAT mulching films (with and without additives) did not exhibit cytotoxic or genotoxic effects.

When BioMP particles enter the gastrointestinal tract, they interact not only with the tissues of internal organs but also with the intestinal microbiota. Jiménez-Arroyo et al. investigated the effects of PLA particles on the intestinal microbiota under simulated digestion conditions [34]. The authors studied PLA particles of two sizes: large (about 5 mm) and small (about 240 μm). The experiment involved simulating the ingestion of a realistic daily amount of polylactic acid (PLA) particles (0.166 g) and their passage through the human gastrointestinal tract, as well as assessing their potential impact on the microbiota of the large intestine. As a result of the digestion simulation, the PLA particles underwent surface changes. Depressions and pores formed on both types of particles due to the hydrolysis of ester bonds in an acidic environment. After the intestinal phase, deposits of salts and organic matter were observed on the surface of both types of PLA particles, which is consistent with the hypothesis of the formation of a ‘protein crown’ [52]. A biofilm also formed on the particles. The formation of a protein corona—a layer of adsorbed proteins on the particle surface—can alter cellular uptake and immune recognition. Similarly, biofilms may form on plastic surfaces, modifying particle–microbe interactions [53]. The simgi^® computerised dynamic system was used to simulate interaction with the microbiota of the large intestine. Although PLA MPs did not have an apparent effect on the homeostasis of the microbial community, they led to structural and functional changes in the human intestinal microbiota. There was a tendency toward an increase in Bifidobacterium levels in the presence of larger PLA particles. In addition to surface interaction, the rise in Bifidobacterium is also associated with increased pullulanase activity, which was predicted by bioinformatic functional analysis. The results show that, despite minor modulation of microbial communities, the presence of biodegradable PLA biopolymer in the human intestine does not hurt the intestinal microbiome.

Thus, it can be noted that the cytotoxicity of micro- and nanoplastics depends on numerous factors, and it is impossible to determine which type of material is safer. From the data presented above, intestinal cells can neutralise MNP particles, even despite their internalisation, with enzymes that can break down small plastic particles playing a role in this process.

There is also a tendency for cancer cells in studies to be more resistant to the effects of microplastics than normal cells [23,33,39], which may be related to their tumour nature and altered metabolism. Therefore, as in the case of the lungs, it is necessary to continue research with longer tests, normal cells, and a wider range of materials and sizes.

3.5. Immune

In addition to interacting with the lungs and digestive system, BioMNP can also enter the bloodstream and interact with the immune system. In their work, Kim et al. investigated the interaction of pure PBS and a composite with added cellulose nanocrystals with normal mouse macrophages RAW 264.7 [35]. In this study, relatively large particles ranging from 125 to 140 μm were used, and concentrations ranged from 0 to 1000 μg/mL. Direct exposure to suspended plastic particles showed a negligible effect on cell viability, with no observable lysis or growth inhibition.

Another study using RAW 264.7 cells used released nanoplastics and oligomers from PLA [22]. The nanoplastics had particle sizes of about 200 nm, and the oligomers had a molecular weight of about 900 Da. Concentrations in in vitro tests ranged from 0.0008 to 0.5 mg/mL. In the case of smaller particles and PLA oligomers, a decrease in MMP12 bioactivity and an increase in C3a, C5a, and TNF-α concentrations in RAW 264.7 cells were observed, indicating inflammation. Oligomers caused a more pronounced inflammatory effect than nanoplastics, confirming the immunoregulatory effect of oligomers.

Another study investigating the cytotoxicity of BioMPs on RAW264.7 cells was conducted by Yu et al. [36]. They examined PLA microplastics that had undergone hydrothermal ageing at 120, 130, and 140 °C. Large particles (600–850 µm) were used at concentrations of 3 and 8 particles per cell well. At low doses, BioMPs did not significantly affect cell viability compared to the control group. However, at high doses (8 particles per well), the effect varied with treatment temperature. Particles treated at 120 °C and 130 °C slightly increased cell viability (by approximately 121.99% and 127.31%, respectively), possibly indicating that cells utilized adsorbed organic compounds as a source of carbon or nutrients. In contrast, particles treated at 140 °C reduced viability to around 83.93% compared to control, suggesting that higher-temperature ageing may promote the release of toxic degradation products. These findings highlight the influence of environmental ageing on BioMNP toxicity and underscore the importance of both dose and degradation history in cytotoxicity assessments.

The article by Jasinski et al. studied the cytotoxicity of spherical microplastic particles made of PLA and cellulose acetate (CA) with mouse liver macrophages, Kupffer cells ImKC and J774A.1 (mouse macrophages). No immediate cytotoxicity was detected for either type of material, or either type of cell, and the same result was obtained in the resazurin assay. In the case of macrophage cell lines (J774A.1 and ImKC), incubation with PLA and CA particles led to a noticeable increase in ROS levels. Previously, it was reported that the identical particles did not increase ROS levels in BNL CL.2 and STC1 cells. The difference in results may be related to particle absorption, as the effect becomes more pronounced with increasing concentration.

The interaction of bioplastics was also studied with human monocytic leukaemia cells THP-1 [32]. Nanoscale particles of PGA, PLA, PBC, and PBAT had a size of about 800 nm. On the first day, all biodegradable plastics exhibited a pronounced proliferative effect, which subsequently slowed down due to the strong phagocytosis of THP-1 cells. Subsequently, PLA showed the highest toxicity, and PGA showed the lowest, as in the case of digestive tract cells. The study also showed that THP-1 cells effectively internalise PGA microplastics over time, with a clear transition from membrane association to intracellular distribution after just 1 h.

Wu et al. found that nanoplastics from UV-aged PLA/PBAT films were toxic to THP-1 cells [37]. The authors filtered the particles in two different ways: centrifugation and ultrafiltration. The diameter of the particles obtained by the first method ranged from 600 to 800 nm, and by ultrafiltration, up to 1 μm; however, most particles were smaller than 300 nm in size. In in vitro experiments, a wide range of concentrations from 0.1 to 1000 mg/L was investigated. As a result, it was shown that MNs released from UV-aged PLA/PBAT films under conditions simulating the gastrointestinal tract affected cell viability in a dose-dependent manner. Upon contact with MNs collected by centrifugation, the viability of THP-1 cells gradually decreased with increasing concentration, falling to 43% at a concentration of 1000 mg/L. When using MNCH collected by ultrafiltration, cell viability was further reduced to approximately 16.7% at 500 mg/L and 9.2% at 1000 mg/L. The EC50 values were 495 mg/L in the first case and 243 mg/L in the second case.

Biodegradable micro- and nanoplastics (BioMNP) can interact with the immune system, eliciting inflammatory responses and oxidative stress in various macrophage and monocyte cell lines. The intensity of the toxic effects depends on particle size, concentration, polymer type, and environmental aging, with oligomers often inducing stronger immunomodulatory effects than nanoplastics.

3.6. Vascular System

Once in the bloodstream, microplastic particles can also interact with the vascular epithelium. Thus, the article by Wang et al. demonstrated that nanoplastics and PLA oligomers can penetrate HUVEC endothelial cells [28]. When interacting with PGA, PBS, PBAT, PLA, and PBC, HUVEC cell proliferation decreased [32]. The effect of three exposure concentrations (1, 25, and 100 mg/L) on cells was not linear, but 25 mg/L had the most significant impact on HUVEC cell viability after three days. PLA again showed the highest toxicity, and PGA showed the lowest. Moreover, compared to PGA, aged PGA showed even lower toxicity. This result differed from previous studies, and it is suggested that this may be because PGA may not release toxic substances during the ageing process. In addition, this study employed natural ageing conditions, which are more representative of real environments, as opposed to accelerated ageing methods.

3.7. Kidney

The last system of the human body not covered in this review is the urinary system. Charoeythornkhajhornchai et al. assessed the cytotoxicity of PLA and PBS microparticles on Vero cells from African green monkeys [24]. The average particle size of PLA and PBS was 4.41 and 7.64 µm, respectively. Concentrations ranging from 6.25 to 100 µg/mL were used for the MTT test, and a concentration of 100 µg/mL was used for the analysis of biomolecular changes. According to the results of the MTT test, all doses of the tested plastics showed non-toxic or low-toxic effects on Vero cells. The maximum decrease in viability was 18% at the maximum PLA concentration. In terms of biomolecular changes, PBS reduced the lipid content, while PLA increased it. PLA also significantly reduced the protein content. The authors concluded that bioplastics (PLA and PBS) had a more pronounced effect on biomolecular changes in renal epithelial cells (Vero) compared to other tested cell lines (NHDF and HaCaT), which may indicate a greater impact on internal tissues.

3.8. Skin

In addition to interacting with internal organs organs such as liver, gut, and lungs, BioMPs can interact with the skin. This section only discusses in vitro studies and does not account for in vivo skin barrier properties. Charoeythornkhajhornchai et al. evaluated the toxicity of PLA and PBS microplastics on HaCaT (human keratinocytes) and NHDF (normal human dermal fibroblasts) cells [24]. The average particle diameter of PLA was 4.41 µm, and that of PBS was 7.64 µm. According to the results of the MTT analysis, an increase in the concentrations of PLA and PBS microplastic particles (from 6.25 to 100 µg/mL) showed a significantly low or practically zero toxic effect on HaCaT cells. Cell viability did not decrease compared to untreated groups. With NHDF cells, BioMPs did not cause toxicity and, in fact, enhanced NHDF cell proliferation at all tested concentrations. Treatment of HaCaT cells with 100 mg/mL PLA for 24 h resulted in a decrease in lipid and ester content, accompanied by an increase in protein content. In this study, ‘ester content’ refers to cellular biomolecular esters detected via synchrotron-based FTIR spectroscopy, particularly the C=O stretching vibration region around 1755–1715 cm⁻¹. The integrated intensity of this spectral band was used to quantify changes in ester-associated functional groups within the cells. PLA exposure decreased cellular ester signals in HaCaT cells, whereas an increase was observed in NHDF and Vero cells, indicating cell line-specific metabolic or structural responses. A significant increase in nucleic acid content was also observed in both cell types. Despite some biomolecular changes that did not lead to a decrease in cell viability, it can be assumed that these plastics are relatively safe for HaCaT and HNDF cells.

Another article evaluated the carcinogenic potential of PLA nanoplastics with mouse fibroblast cells Bhas 42 [38]. The average PLA particle size was 211.78 nm. The article by Domenech et al. showed that PLA nanoplastics (in a wide range of concentrations from 6.25 to 200 μg/mL) did not show an increase in the number of transformed foci under either initiation or promotion conditions. This indicates that PLA does not act as a tumour initiator or promoter in this analysis. Despite high internalisation into Bhas42 cells, PLA nanoparticles did not affect cell proliferation.

Preliminary evidence suggests that PLA-based micro- and nanoplastics exhibit limited cytotoxicity toward skin-related cell lines, although further investigation is warranted. No carcinogenic hazard was detected in the analysis with Bhas42 cells. Future studies should evaluate BioMNP penetration through intact stratum corneum in organotypic or ex vivo models.

4. Conclusions

This review demonstrates that biodegradable micro- and nanoplastics (BioMNP) can interact with human cells from multiple organ systems and may induce cytotoxic effects, including inflammation, oxidative stress, membrane disruption, and reduced cell viability. The summary of the possible toxic effects is shown in Figure 6. While some materials—such as polyglycolic acid (PGA)—show relatively low toxicity, others, particularly PLA-based micro- and nanoplastics and their oligomers, can cause significant biological responses.

Notably, the toxicity of BioMNP is influenced by a range of factors, including particle size, polymer type, concentration, degradation products, and the presence of chemical additives. In vitro and in vivo studies confirm that BioMNP may accumulate in organs and affect physiological functions.

Although many studies report low or moderate toxicity, the variability in experimental designs, cell types, and exposure conditions makes it difficult to draw definitive conclusions. More comprehensive and standardised testing is needed to understand the biological impact of these materials better.

5. Recommendations for Future Research and Regulation

All the articles reviewed have some shortcomings that still limit our knowledge of the cytotoxic effects of biomaterials on living organisms.

The actual concentrations of microplastic consumption are not precisely known. Currently, the literature provides only very broad ranges, which also fail to distinguish between conventional microplastics and biodegradable ones. This is due to the low prevalence of biodegradable plastics. There is also a complete lack of data on the consumption of nanoplastics. Therefore, modern studies often use approximate concentrations or a wide range of concentrations, including extremely high ones. An accurate quantitative assessment of MNP and BioMNP levels in the environment is necessary to model actual consumption in future studies accurately.

The currently available results of the literature studies clearly show that the cytotoxic effects of bio-MPs on living organisms and ecosystems depend on many factors, including their composition, concentration, and size. Unfortunately, the relative contribution of each factor to the potential risks associated with bio-MPs cannot be easily deduced due to the lack of comparative laboratory studies sensitive to changes in these relevant parameters. Additional analysis is required to fill this knowledge gap.

Another limitation is the use of mainly pristine plastic, studied primarily under strictly controlled conditions. Only a few studies have examined the impact of weathered biopolymer (BioMP). When released into the environment, bioplastics are exposed to ultraviolet radiation, moisture, and various chemical, physical, and biological factors, which cause changes in their size, structure, surface chemical composition, and morphology. Therefore, future research should pay particular attention to weathered microplastic and BioMNP particles.

Research usually focuses on the impact of only one material per experiment; mixtures are rarely used, and their interaction is often not considered. Therefore, it is vital in future work to investigate mixtures of biopolymer microplastics (BioMNP) and microplastics (MNP) in proportions that reflect real-world conditions. In such cases, the interaction of the mixture components can either weaken or enhance the adverse effects of their impact.

In addition, more attention needs to be paid to plastics that are widely used for commercial purposes. As shown in several studies, these materials can be hazardous due to the additives they contain. In the future, it will be essential to study not only the quantity of these additives but also the mechanisms by which they are released from the polymer matrix. This will enable further reduction of harmful component concentrations, the selection of safer alternatives, and a decrease in the number of similar additives that serve the same functions.

There is not yet enough data in the literature on the toxicity of BioMPs to develop standards. To assist in this area, it is also necessary to conduct tests of chronic and repeated interaction of micro- and nanoplastics with living cells. This will enable us to simulate real-life situations in this field.

Further research in this area should be conducted with these aspects in mind. More different cells and materials should be studied over more extended periods. Establishing a robust body of evidence is essential to determine whether current strategies effectively mitigate the risks posed by microplastic pollution. Some studies suggest that cellular adaptation to BioMNP exposure is possible; however, such adaptation is likely to be accompanied by cellular stress or damage.