Preferred Lung Accumulation of Polystyrene Nanoplastics with Negative Charges.

With the increasing presence of nanoplastics (NPs) in the human bloodstream, it is urgent to investigate their tissue accumulation and potential health risks. This study examines the effects of the size and surface charges of polystyrene (PS) NPs on lung accumulation. Using magnetic separation, we identified the protein corona composition on iron-core PS NPs, revealing the enrichment of vitronectin and fibrinogen. The corona promotes integrin αIIbß3 receptor-mediated uptake by lung endothelial cells, explaining that both the corona composition and protein structure determine preferred localization of negatively charged PS NPs in the lung. This study uncovers the role of protein corona in NP uptake and the way NPs enter the lung, emphasizing the need to consider interactions between nanoplastics with varying surface characteristics and biological molecules in the nanotoxicological field.

Photoaged Nanopolystyrene Affects Neurotransmission to Induce Transgenerational Neurotoxicity in Caenorhabditis elegans.

Nanopolystyrene (NPS), a frequently employed nanoplastic, is an emerging environmental contaminant known to cause neurotoxicity in various organisms. However, the potential for transgenerational neurotoxic effects, especially from photoaged NPS (P-NPS), remains underexplored. This study investigated the aging of virgin NPS (V-NPS) under a xenon lamp to simulate natural sunlight exposure, which altered the physicochemical characteristics of the NPS. The parental generation (P0) of Caenorhabditis elegans was exposed to environmental concentrations (0.1-100 µg/L) of V-NPS and P-NPS, with subsequent offspring (F1-F4 generations) cultured under NPS-free conditions. Exposure to 100 µg/L P-NPS resulted in more pronounced deterioration in locomotion behavior in the P0 generation compared to V-NPS; this deterioration persisted into the F1-F2 generations but returned to normal in the F3-F4 generations. Additionally, maternal exposure to P-NPS damaged dopaminergic, glutamatergic, and serotonergic neurons in subsequent generations. Correspondingly, there was a significant decrease in the levels of dopamine, glutamate, and serotonin, associated with reduced expression of neurotransmission-related genes dat-1, eat-4, and tph-1 in the P0 and F1-F2 generations. Further analysis showed that the effects of P-NPS on locomotion behavior were absent in subsequent generations of eat-4(ad572), tph-1(mg280), and dat-1(ok157) mutants, highlighting the pivotal roles of these genes in mediating P-NPS-induced transgenerational neurotoxicity. These findings emphasize the crucial role of neurotransmission in the transgenerational effects of P-NPS on locomotion behavior, providing new insights into the environmental risks associated with exposure to photoaged nanoplastics.

Intrinsic Peroxidase-like Activity of Polystyrene Nanoplastics Mediates Oxidative Stress.

Nanoplastics represent a global environmental concern due to their ubiquitous presence and potential adverse impacts on public and environmental health. There is a growing need to advance the mechanistic understanding of their reactivity as they interact with biological and environmental systems. Herein, for the first time, we report that polystyrene nanoplastics (PSNPs) have intrinsic peroxidase-like activity and are able to mediate oxidative stress. The peroxidase-like activity is dependent on temperature and pH, with a maximum at pH 4.5 and 40 °C. The catalytic activity exhibits saturation kinetics, as described by the Michaelis-Menten model. The peroxidase-like activity of PSNPs is attributed to their ability to mediate electron transfer from peroxidase substrates to H2O2. Ozone-induced PSNP aging can introduce oxygen-containing groups and disrupt aromatic structures on the nanoplastic surface. While ozonation initially enhances peroxidase-like activity by increasing oxygen-containing groups without degrading many aromatic structures, extended ozonation destroys aromatic structures, significantly reducing this activity. The peroxidase-like activity of PSNPs can mediate oxidative stress, which is generally positively correlated with their aromatic structures, as suggested by the ascorbic acid assay. These results help explain the reported oxidative stress exerted by nanoplastics and provide novel insights into their environmental and public health implications.

Confocal Surface-Enhanced Raman Imaging of the Intestinal Barrier Crossing Behavior of Model Nanoplastics in Daphnia Magna.

Nanoplastics (nP) pose hazards to aquatic animals once they are ingested. Significant knowledge gaps exist regarding the nP translocation across the animal intestine, which is the first barrier between the ingested nP and the animal body. We examined the intestinal barrier crossing behavior of nP in an aquatic animal model (Daphnia magna) and determined the translocation mechanism with the help of model "core-shell" polystyrene nanoplastics (nPS) and confocal surface-enhanced Raman spectroscopy (SERS). The Raman reporter (4-mercaptobenzoic acid)-tagged gold "core" of the model nPS enables sensitive and reliable particle imaging by confocal SERS. This method detected SERS signals of model nPS concentration as low as 4.1 × 109 particles/L (equivalent to 0.27 µg/L PS "shell" concentration). The translocation was observed with the help of multilayer stacked Raman maps of SERS signals of the model nPS. With a higher concentration or longer exposure time of the model nPS, uptake and translocation of the plastic particles increased. In addition, we demonstrated that clathrin-dependent endocytosis and macropinocytosis were two major mechanisms underlying the translocation. This study contributes to a mechanistic understanding of nP translocation by using the pioneering model nPS and an analytical toolkit, which undergird further investigations into nP behavior and health effects in aquatic species.

Inhibiting ferroptosis in brain microvascular endothelial cells: A potential strategy to mitigate polystyrene nanoplastics‒induced blood‒brain barrier dysfunction.

Polystyrene nanoplastics (PS-NPs), a group of ubiquitous pollutants, may injure the central nervous system through the blood‒brain barrier (BBB). However, whether exposure to PS-NPs contributes to BBB disruption and the underlying mechanisms are still unclear. In vivo, we found that PS-NPs (25 mg/kg BW) could significantly increase BBB permeability in mice and downregulate the distribution of the tight junction-associated protein zona occludens 1 (ZO-1) in brain microvascular endothelial cells (BMECs). Using an in vitro BBB model, exposure to PS-NPs significantly reduced the transendothelial electrical resistance and altered ZO-1 expression and distribution in a dose-dependent manner. RNA-seq analysis and functional investigations were used to investigate the molecular pathways involved in the response to PS-NPs. The results revealed that the ferroptosis and glutathione metabolism signaling pathways were related to the disruption of the BBB model caused by the PS-NPs. PS-NPs treatment promoted ferroptosis in bEnd.3 cells by inducing disordered glutathione metabolism in addition to Fe2+ and lipid peroxide accumulation, while suppressing ferroptosis with ferrostatin-1 (Fer-1) suppressed ferroptosis-related changes in bEnd.3 cells subjected to PS-NPs. Importantly, Fer-1 alleviated the decrease in ZO-1 expression in bEnd.3 cells and the exacerbation of BBB damage induced by PS-NPs. Collectively, our findings suggest that inhibiting ferroptosis in BMECs may serve as a potential therapeutic target against BBB disruption induced by PS-NPs exposure.

Protective effect of Cordycepin on blood-testis barrier against pre-puberty polystyrene nanoplastics exposure in male rats.

Plastic pollution is an emerging environmental issue, with microplastics and nanoplastics raising health concerns due to bioaccumulation. This work explored the impact of polystyrene nanoparticle (PS-NPs) exposure during prepuberty on male reproductive function post maturation in rats. Rats were gavaged with PS-NPs (80 nm) at 0, 3, 6, 12 mg/kg/day from postnatal day 21 to 95. PS-NPs accumulated in the testes and reduced sperm quality, serum reproductive hormones, and testicular coefficients. HE staining showed impaired spermatogenesis. PS-NPs disrupted the blood-testis barrier (BTB) by decreasing junction proteins, inducing inflammation and apoptosis. Transcriptomics identified differentially expressed genes related to metabolism, lysosome, apoptosis, and TLR4 signaling. Molecular docking revealed Cordycepin could compete with polystyrene for binding to TLR4. Cordycepin alleviated oxidative stress and improved barrier function in PS-NPs treated Sertoli cells. In conclusion, prepubertal PS-NPs exposure induces long-term reproductive toxicity in male rats, likely by disrupting spermatogenesis through oxidative stress and BTB damage. Cordycepin could potentially antagonize this effect by targeting TLR4 and warrants further study as a protective agent. This study elucidates the mechanisms underlying reproductive toxicity of PS-NPs and explores therapeutic strategies.

Exposure to high dose of polystyrene nanoplastics causes trophoblast cell apoptosis and induces miscarriage.

BACKGROUND: With rapid increase in the global use of various plastics, microplastics (MPs) and nanoplastics (NPs) pollution and their adverse health effects have attracted global attention. MPs have been detected out in human body and both MPs and NPs showed female reproductive toxicological effects in animal models. Miscarriage (abnormal early embryo loss), accounting for 15-25% pregnant women worldwide, greatly harms human reproduction. However, the adverse effects of NPs on miscarriage have never been explored. RESULTS: In this study, we identified that polystyrene (PS) plastics particles were present in women villous tissues. Their levels were higher in villous tissues of unexplained recurrent miscarriage (RM) patients vs. healthy control (HC) group. Furthermore, mouse assays further confirmed that exposure to polystyrene nanoplastics (PS-NPs, 50 nm in diameter, 50 or 100 mg/kg) indeed induced miscarriage. In mechanism, PS-NPs exposure (50, 100, 150, or 200 µg/mL) increased oxidative stress, decreased mitochondrial membrane potential, and increased apoptosis in human trophoblast cells by activating Bcl-2/Cleaved-caspase-2/Cleaved-caspase-3 signaling through mitochondrial pathway. The alteration in this signaling was consistent in placental tissues of PS-NPs-exposed mouse model and in villous tissues of unexplained RM patients. Supplement with Bcl-2 could efficiently suppress apoptosis in PS-NPs-exposed trophoblast cells and reduce apoptosis and alleviate miscarriage in PS-NPs-exposed pregnant mouse model. CONCLUSIONS: Exposure to PS-NPs activated Bcl-2/Cleaved-caspase-2/Cleaved-caspase-3, leading to excessive apoptosis in human trophoblast cells and in mice placental tissues, further inducing miscarriage.

Polystyrene nanoplastics induce apoptosis, autophagy, and steroidogenesis disruption in granulosa cells to reduce oocyte quality and fertility by inhibiting the PI3K/AKT pathway in female mice.

BACKGROUND: Nanoplastics (NPs) are emerging pollutants that pose risks to living organisms. Recent findings have unveiled the reproductive harm caused by polystyrene nanoparticles (PS-NPs) in female animals, yet the intricate mechanism remains incompletely understood. Under this research, we investigated whether sustained exposure to PS-NPs at certain concentrations in vivo can enter oocytes through the zona pellucida or through other routes that affect female reproduction. RESULTS: We show that PS-NPs disrupted ovarian functions and decreased oocyte quality, which may be a contributing factor to lower female fertility in mice. RNA sequencing of mouse ovaries illustrated that the PI3K-AKT signaling pathway emerged as the predominant environmental information processing pathway responding to PS-NPs. Western blotting results of ovaries in vivo and cells in vitro showed that PS-NPs deactivated PI3K-AKT signaling pathway by down-regulating the expression of PI3K and reducing AKT phosphorylation at the protein level, PI3K-AKT signaling pathway which was accompanied by the activation of autophagy and apoptosis and the disruption of steroidogenesis in granulosa cells. Since PS-NPs penetrate granulosa cells but not oocytes, we examined whether PS-NPs indirectly affect oocyte quality through granulosa cells using a granulosa cell-oocyte coculture system. Preincubation of granulosa cells with PS-NPs causes granulosa cell dysfunction, resulting in a decrease in the quality of the cocultured oocytes that can be reversed by the addition of 17ß-estradiol. CONCLUSIONS: This study provides findings on how PS-NPs impact ovarian function and include transcriptome sequencing analysis of ovarian tissue. The study demonstrates that PS-NPs impair oocyte quality by altering the functioning of ovarian granulosa cells. Therefore, it is necessary to focus on the research on the effects of PS-NPs on female reproduction and the related methods that may mitigate their toxicity.

Polystyrene nanoplastics induced learning and memory impairments in mice by damaging the glymphatic system.

The excessive usage of nanoplastics (NPs) has posed a serious threat to the ecological environment and human health, which can enter the brain and then result in neurotoxicity. However, research on the neurotoxic effects of NPs based on different exposure routes and modifications of functional groups is lacking. In this study, the neurotoxicity induced by NPs was studied using polystyrene nanoplastics (PS-NPs) of different modifications (PS, PS-COOH, and PS-NH2). It was found that PS-NH2 through intranasal administration (INA) exposure route exhibited the greatest accumulation in the mice brain after exposure for 7 days. After the mice were exposed to PS-NH2 by INA means for 28 days, the exploratory ability and spatial learning ability were obviously damaged in a dose-dependent manner. Further analysis indicated that these damages induced by PS-NH2 were closely related to the decreased ability of glymphatic system to clear ß-amyloid (Aß) and phosphorylated Tau (P-Tau) proteins, which was ascribed to the loss of aquaporin-4 (AQP4) polarization in the astrocytic endfeet. Moreover, the loss of AQP4 polarization might be regulated by the NF-κB pathway. Our current study establishes the connection between the neurotoxicity induced by PS-NPs and the glymphatic system dysfunction for the first time, which will contribute to future research on the neurotoxicity of NPs.

Integrated transcriptomics and metabolomics reveal the mechanism of polystyrene nanoplastics toxicity to mice.

Microplastic (MP) are an emerging environmental pollutant, which has toxic effects on organisms, and it has received extensive attention currently. Studying the transcriptomic and metabolic responses of mice to nanoplastic-contaminated water is critical for understanding molecular-level toxicity of nanoplastics (NPs), but there are few studies on this topic. To analyze the effects of different concentrations of polystyrene (PS) nanoplastic-contaminated water on mice at the transcriptome and metabolism of spleens to study the molecular toxicity. Here, testing of histopathology of spleen of female mice was performed after drinking water containing 0.1 µm PS-NPs (1 mg/mL and 50 mg/mL) at different concentrations for 49 days, respectively. The spleen tissue samples were subjected to metabolome and transcriptome sequencing. Four differentially expressed genes were randomly chosen for qRT-PCR to confirm the correctness of transcriptome sequencing. Common Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that a large number of differential genes and differential metabolites mainly focused on immune, inflammation, neurodegenerative disease, cardiovascular disease, nervous, etc. in the organism systems module; lipid, amino acid, taurine and hypotaurine metabolisms, etc. in the metabolism module; signaling translation, signaling molecules and interaction, and neuroactive ligand-receptor interaction, etc. in the environmental information processing. The results showed that pathway analysis at transcriptome and metabolome levels confirmed that the immune system of mice was affected after drinking water contaminated with polystyrene nanoplastics.

Polystyrene nanoplastics at predicted environmental concentrations enhance the toxicity of copper on Caenorhabditis elegans.

Excessive nanoplastics not only pose a direct threat to the environment but also have the propensity to adsorb and interact with other pollutants, exacerbating their impact. The coexistence of nanoplastics and heavy metals in soils is a prevalent phenomenon. However, limited research existed about the joint effects of the two contaminants on soil organisms. In this paper, we ascertained the combined toxicity of polystyrene nanoplastics (PS-NPs) and copper (Cu2+) on soil organisms (Caenorhabditis elegans) at quantities that were present in the environment, further exploring whether the two toxicants were synergistic or antagonistic. The outcomes manifested that single exposure to low-dose PS-NPs (1 µg/L) would not cause significant damage to nematodes. After treatment with PS-NPs and Cu2+, the locomotion ability of nematode was impaired, accompanied by an elevation in reactive oxygen species (ROS) level and a biphasic response in antioxidant enzyme activity. Moreover, combined exposure to PS-NPs and Cu2+ induced the mRNA up-regulation of vit-6, cyp-35a2, hsp-16.2, age-1, and cep-1, both of which were stress-related genes. The comparative analysis between groups (with or without PS-NPs) revealed that the combined exposure group resulted in significantly greater toxic effects on nematodes compared with Cu2+ exposure alone. Furthermore, the addition of PS-NPs influenced the metabolic profiles of Caenorhabditis elegans under Cu2+ stress, with numerous differential metabolites associated with oxidative damage or defense mechanism. Overall, these findings manifested that PS-NPs at the expected environmental concentration elevated Cu2+ toxicity on nematodes.

Polystyrene nanoplastics exposure triggers spermatogenic cell senescence via the Sirt1/ROS axis.

Polystyrene nanoplastics (PS-NPs) have been reported to accumulate in the testes and constitute a new threat to reproductive health. However, the exact effects of PS-NPs exposure on testicular cells and the underlying mechanisms remain largely unknown. The C57BL/6 male mice were orally administered with PS-NPs (80 nm) at different dosages (0, 10, and 40 mg/kg/day) for 60 days, and GC-1 cells were treated with PS-NPs in this study. Enlarged seminiferous tubule lumens and a loose and vacuolated layer of spermatogenic cells were observed in PS-NPs-exposed mice. Spermatogenic cells which may be one of the target cells for this reproductive damage, were decreased in the mice from PS-NPs group. PS-NPs caused spermatogenic cells to undergo senescence, manifested as elevated SA-ß-galactosidase activity and activated senescence-related signaling p53-p21/Rb-p16 pathways, and induced cell cycle arrest. Mechanistically, Gene Ontology (GO) enrichment suggested the key role of reactive oxygen species (ROS) in PS-NPs-induced spermatogenic cell senescence, and this result was confirmed by measuring ROS levels. Moreover, ROS inhibition partially attenuated the senescence phenotype of spermatogenic cells and DNA damage. Using the male health atlas (MHA) database, Sirt1 was filtrated as the critical molecule in the regulation of testicular senescence. PS-NPs induced overexpression of the main ROS generator Nox2, downregulated Sirt1, increased p53 and acetylated p53 in vivo and in vitro, whereas these disturbances were partially restored by pterostilbene. In addition, pterostilbene intervention significantly alleviated the PS-NPs-induced spermatogenic cell senescence and attenuated ROS burst. Collectively, our study reveals that PS-NPs exposure can trigger spermatogenic cell senescence mediated by p53-p21/Rb-p16 signaling by regulating the Sirt1/ROS axis. Importantly, pterostilbene intervention may be a promising strategy to alleviate this damage.

Chronic exposure to polystyrene nanoplastics induces intestinal mechanical and immune barrier dysfunction in mice.

Micro(nano)plastics are prevalent in the environment, and prolonged exposure to them represents a threat to human health. The goal of this study is to assess the health risk of long-term exposure to nanoplastics (NPs) at environmental concentrations on the intestinal mechanical and immune barrier in mice. In this study, mice were provided drinking water containing polystyrene NPs (PS-NPs; 0.1, 1, and 10 mg·L-1) for 32 consecutive weeks. The levels of endocytosis proteins caveolin and clathrin and of tight junctional proteins claudin-1, occludin, and ZO-1, and morphological changes, proportion of lymphocytes B in MLNs and lymphocytes T in IELs and LPLs were determined by immunohistochemistry, hematoxylin-eosin, and flow cytometry assays in the intestinal tissues of mice at 28 weeks. The activities or concentrations of ROS, SOD, MDA, and GSH-Px and inflammatory factors (IL-1ß, IL-6, and TNF-α) in the intestinal tissues of mice were measured by ELISA at 12, 16, 20, 24, and 32 weeks. Compared with the control group, oral ingested PS-NPs entered the intestinal tissues of mice and upregulated expression levels of the clathrin and caveolin. The intestinal tissue structure of mice in the PS-NPs (1 and 10 mg·L-1) exposure groups showed significant abnormalities, such as villus erosion, decreased of crypts numbers and large infiltration of inflammatory cells. Exposure to 0.1 mg·L-1 PS-NPs decreased occludin protein levels, but not claudin-1 and ZO-1 levels. The levels of these three tight junction proteins decreased significantly in the 1 and 10 mg·L-1 PS-NPs exposed groups. Exposure to PS-NPs led to a significant time- and dose-dependent increase in ROS and MDA levels, and concurrently decreased GSH-Px and SOD contents. Exposure to PS-NPs increased the proportion of B cells in MLNs, and decreased the proportion of CD8+ T cells in IELs and LPLs. The levels of pro-inflammatory cytokines IL-6, TNF-α and IL-1ß were markedly elevated after PS-NPs exposure. Long-term PS-NPs exposure impaired intestinal mechanical and immune barrier, and indicate a potentially significant threat to human health.

Nanoplastics exposure-induced mitochondrial dysfunction contributes to disrupted stem cell differentiation in human cerebral organoids.

Nanoplastics are ubiquitous in our daily lives, raising concerns about their potential impact on the human brain. Many studies reported that nanoplastics permeate the blood-brain barrier and influence cellular processes in mouse models. However, the neurotoxic effects of ingesting nanoplastics on human brain remain poorly understood. Here, we treated cerebral organoids with polystyrene nanoplastics to model the effects of nanoplastic exposure on human brain. Importantly, we found that mitochondria might be the significant organelles affected by polystyrene nanoplastics using immunostaing and RNA-seq analysis. Subsequently, we observed the increased cell death and decreased cell differentiation in our cerebral organoids. In conclusion, our findings shed insights on the mechanisms underlying the toxicity of nanoplastics on human brain organoids, providing an evaluation system in detection potential environmental toxicity on human brain.

Influence of algal-extracellular polymeric substances (EPS) on the pristine and combined toxicity of TiO2 NPs and PSNPs in Artemia salina: Eco-corona enhances the toxic effects.

The study on the influence of Natural Organic Matter (NOM) over the individual and combined effects of different nanomaterials on marine species is pertinent. The current study explores the role of Extracellular Polymeric Substances (EPS) in influencing the individual and combined toxic effects of polystyrene nanoplastics (PSNPs) viz. aminated (NH2-PSNPs), carboxylated (COOH-PSNPs), and plain PSNPs and TiO2 NPs in the marine crustacean, Artemia salina. A. salina was interacted with pristine PSNPs, pristine TiO2 NPs, EPS incubated PSNPs, EPS incubated TiO2 NPs, binary mixture of PSNPs and TiO2 NPs, and EPS adsorbed binary mixture of PSNPs and TiO2 NPs for 48 h. The present study proves that, when compared to the pristine toxicity of PSNPs and TiO2 NPs, the coexposure of TiO2 NPs with PSNPs resulted in increased toxicity. The adsorption of algal EPS on the NMs (both in their pristine and combined forms) significantly increased the toxic nature of the NMs against A. salina. It was observed that with an increase in the hydrodynamic diameter of the particles, the mortality, oxidative stress, and ingestion of the NMs by A. salina increased. The uptake of Ti by A. salina from 8 mg/L TiO2 NPs, EPS adsorbed 8 mg/L TiO2 NPs, 8 mg/L TiO2 NPs + NH2-PSNPs and the EPS adsorbed mixture of 8 mg/L TiO2 NPs, 8 mg/L TiO2 NPs + NH2-PSNPs was observed to be 0.043, 0.047, 0.186, and 0.307 mg/g of A. salina. The adsorption of algal EPS on the NMs (both in their pristine and combined forms) significantly increased the toxic nature of the NMs against A. salina. The major outcomes from the current study highlight the role of EPS in exacerbating the toxicity of NMs in marine crustaceans.

Heteroaggregation and deposition behaviors of carboxylated nanoplastics with different types of clay minerals in aquatic environments: Important role of calcium(II) ion-assisted bridging.

The widespread utilization of plastic products ineluctably leads to the ubiquity of nanoplastics (NPs), causing potential risks for aquatic environments. Interactions of NPs with mineral surfaces may affect NPs transport, fate and ecotoxicity. This study aims to investigate systematically the deposition and aggregation behaviors of carboxylated polystyrene nanoplastics (COOH-PSNPs) by four types of clay minerals (illite, kaolinite, Na-montmorillonite, and Ca-montmorillonite) under various solution chemistry conditions (pH, temperature, ionic strength and type). Results demonstrate that the deposition process was dominated by electrostatic interactions. Divalent cations (i.e., Ca2+, Mg2+, Cd2+, or Pb2+) were more efficient for screening surface negative charges and compressing the electrical double layer (EDL). Hence, there were significant increases in deposition rates of COOH-PSNPs with clay minerals in suspension containing divalent cations, whereas only slight increases in deposition rates of COOH-PSNPs were observed in monovalent cations (Na+, K+). Negligible deposition occurred in the presence of anions (F-, Cl-, NO3-, CO32-, SO42-, or PO43-). Divalent Ca2+ could incrementally facilitate the deposition of COOH-PSNPs through Ca2+-assisted bridging with increasing CaCl2 concentrations (0-100 mM). The weakened deposition of COOH-PSNPs with increasing pH (2.0-10.0) was primarily attributed to the reduce in positive charge density at the edges of clay minerals. In suspensions containing 2 mM CaCl2, increased Na+ ionic strength (0-100 mM) and temperature (15-55 ◦C) also favored the deposition of COOH-PSNPs. The ability of COOH-PSNPs deposited by four types of clay minerals followed the sequence of kaolinite > Na-montmorillonite > Ca-montmorillonite > illite, which was related to their structural and surface charge properties. This study revealed the deposition behaviors and mechanisms between NPs and clay minerals under environmentally representative conditions, which provided novel insights into the transport and fate of NPs in natural aquatic environments.

Co-exposure of arsenic and polystyrene-nanoplastics induced kidney injury by disrupting mitochondrial homeostasis and mtROS-mediated ferritinophagy and ferroptosis.

Arsenic (As) and polystyrene nanoplastics (PSNPs) co-exposure induced biotoxicity and ecological risks have attracted wide attention. However, the combined effects of As and PSNPs on the kidney and their underlying mechanisms of toxicities remain to be explored. Here, we investigated the effects of As and PSNPs co-exposure on structure and function in mice kidney, and further explored the possible mechanisms. In this study, we identified that co-exposure to As and PSNPs exhibited conspicuous renal structural damage and pathological changes, accompanied by renal tissue fibrosis (increased protein expression of Collagen I and α-SMA and deposition of collagen fibers), whereas alone exposure to As or PSNPs does not exhibit nephrotoxicity. Subsequently, our results further showed that combined action of As and PSNPs induced mitochondrial oxidative damage and impaired mitochondrial dynamic balance. Furthermore, co-treatment with As and PSNPs activated NCOA4-mediated ferritinophagy and ferroptosis in mice kidney and TCMK-1 cells, which was confirmed by the changes in the expression of ferritinophagy and ferroptosis related indicators (NCOA4, LC3, ATG5, ATG7, FTH1, FTL, GPX4, SLC7A11, FSP1, ACSL4 and PTGS2). Meaningfully, pretreatment with the mtROS-targeted scavenger Mito-TEMPO significantly attenuated As and PSNPs co-exposure induced mitochondrial damage, ferritinophagy and ferroptosis. In conclusion, these findings demonstrated that mtROS-dependent ferritinophagy and ferroptosis are important factors in As and PSNPs co-exposure induced kidney injury and fibrosis. This study provides a new insight into the study of combined toxicity of nanoplastics and heavy metal pollutants.

Combined exposure of nano-titanium dioxide and polystyrene nanoplastics exacerbate oxidative stress-induced liver injury in mice by regulating the Keap-1/Nrf2/ARE pathway.

It is well known that polystyrene nanoplastics (PS-NaP) and nano-titanium dioxide (TiO2 NPs) are frequently co-appeared in daily life and can cause liver injury when they accumulate in the liver. Nonetheless, the combined toxicological impacts and potential molecular mechanisms of PS-NaP and TiO2 NPs in the hepatic system have not been revealed. Thus, we conducted experiments on C57BL/6 mice exposed to PS-NaP or/and TiO2 NPs for 4 weeks. The findings suggested that PS-NaP and TiO2 NPs co-exposed significantly altered the hepatic function parameters, levels of antioxidant-related enzymes and genes expression of Keap-1/Nrf2/ARE signaling pathway, as well as significantly increased the hepatic Ti contents, aggravated hepatic pathological and oxidative stress (OS) damage compared with individual exposure to PS-NaP or TiO2 NPs. Using N-Acetyl-L-cysteine (NAC), an OS inhibitor, we further demonstrated that OS played a pivotal role in coexposure-induced liver injury. NAC reduced the levels of OS in mice, which mitigated co-exposure-induced liver injury. Taken together, we proposed that PS-NaP and TiO2 NPs co-exposed activated the Keap-1, then inhibited the recognition of Nrf2 and ARE, consequently exacerbated liver injury. These findings shed light on the co-toxicity and potential mechanism of nanoplastics and nanoparticles, which informed the risk assessment of human exposure to environmental pollutants.

Enhanced hepatic metabolic perturbation of polystyrene nanoplastics by UV irradiation-induced hydroxyl radical generation.

The environmental behavior of and risks associated with nanoplastics (NPs) have attracted considerable attention. However, compared to pristine NPs, environmental factors such as ultraviolet (UV) irradiation that lead to changes in the toxicity of NPs have rarely been studied. We evaluated the changes in morphology and physicochemical properties of polystyrene (PS) NPs before and after UV irradiation, and compared their hepatotoxicity in mice. The results showed that UV irradiation caused particle size reduction and increased the carbonyl index (CI) and negative charge on the particle surface. UV-aged PS NPs (aPS NPs) could induce the generation of hydroxyl radicals (·OH), but also further promoted the generation of ·OH in the Fenton reaction system. Hepatic pathological damage was more severe in mice exposed to aPS NPs, accompanied by a large number of vacuoles and hepatocyte balloon-like changes and more marked perturbations in blood glucose and serum lipoprotein, alanine aminotransferase and aspartate aminotransferase levels. In addition, exposure to PS NPs and aPS NPs, especially aPS NPs, triggered oxidative stress and significantly damaged the antioxidant capacity of mice liver. Compared with PS NPs, exposure to aPS NPs increased the number of altered metabolites in hepatic and corresponding metabolic pathways, especially glutathione metabolism. Our research suggests that UV irradiation can disrupt the redox balance in organisms by promoting the production of ·OH, enhancing PS NPs-induced liver damage and metabolic disorders. This study will help us understand the health risks of NPs and to avoid underestimation of the risks of NPs in nature.

Aging of Nanoplastics Significantly Affects Protein Corona Composition Thus Enhancing Macrophage Uptake.

Nanoplastics (NPs), as emerging contaminants, have attracted increasing attention for their effects on human exposure and potential health risks. The protein corona formed on the surface of NPs affects the biological activity and fate of the NPs in vivo. However, how environmental aging, an inevitable process once NPs enter the environment, affects the formation of protein corona on NPs is still unclear. This study investigated the changes in the compositions of protein corona formed on photo-aged polystyrene (PS) NPs in human bronchoalveolar lavage fluid (BALF), corresponding to the inhalation exposure pathway. The results demonstrated that both the species and abundance of proteins in the BALF protein corona on the surface of PS NPs were altered by aging. In addition, the aged PS NPs are more hydrophilic and less electronegative than the pristine PS NPs; hence, there is an increased sorption of more negatively charged hydrophilic proteins. Moreover, aging-induced alterations in BALF protein corona enhanced the uptake of aged PS NPs by lung macrophages J774A.1 through phagocytosis and clathrin-mediated endocytosis. These findings highlight the importance of environmental aging processes in the biosafety assessment of nanoplastics.