Quantifying Nanoplastic Toxicity Using Gold-Core Polystyrene Nanoparticles: In vivo Evaluation and Human Risk Extrapolation

Yingzi Cui,1,* Xiaohan Tong,1,* Jiawang Ding,2 Boqing Li,1 Wenke Wang,1 Chunlei Ma,1 Zhiqin Li,1 Ying Zhang1 1School of Basic Medical Sciences, Binzhou Medical University, Yantai, Shandong, People’s Republic of China; 2CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Zhang, School of Basic Medicine, Binzhou Medical University, 346 Guanhai Road, Yantai, Shandong, People’s Republic of China, Tel +86 535 6913209, Email [email protected] Boqing Li, School of Basic Medicine, Binzhou Medical University, 346 Guanhai Road, Yantai, Shandong, People’s Republic of China, Tel +86 535 6913069, Email [email protected]: Nanoplastics (NPs) are widespread environmental pollutants that pose risks to human health; however, risk thresholds for NPs accumulation in human tissues remain poorly defined. This study validates gold-core polystyrene nanoplastics (AuPS-NPs) as a quantifiable proxy for polystyrene nanoplastics (PS-NPs) to evaluate toxicity and bioaccumulation at environmentally relevant concentrations, with extrapolation to human health implications.Methods: AuPS-NPs were synthesized with a gold core and polystyrene shell, characterized by transmission electron microscopy (TEM) and quantified by inductively coupled plasma mass spectrometry (ICP-MS). In vitro, human gastric adenocarcinoma (AGS) and human colorectal adenocarcinoma (Caco-2) cells were exposed to AuPS-NPs or PS-NPs to assess cytotoxicity, reactive oxygen species generation, and mitochondrial membrane depolarization. In vivo, BALB/c mice were orally exposed to AuPS-NPs (1 and 10 mg/L) for 98 days, followed by evaluation of intestinal accumulation, body weight, organ indices, and biomarkers of inflammation, lipid metabolism, energy metabolism, and oxidative stress. A toxicokinetic–toxicodynamic (TK–TD) model was developed to simulate NPs accumulation, dose–response relationships, and human risk thresholds.Results: AuPS-NPs and PS-NPs showed comparable concentration-dependent cytotoxicity in vitro. In vivo, chronic AuPS-NP exposure caused intestinal accumulation, body weight reduction, increased organ indices, and biomarker perturbations including interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), triglycerides (TG), total cholesterol (T-CHO), adenosine triphosphate (ATP), lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD). TK–TD modeling yielded a human intestinal toxicity threshold of 9.529 × 105 particles/kg, providing a particle-based reference for risk extrapolation.Conclusion: AuPS-NPs replicate PS-NPs toxicity and enable quantitative risk assessment. Chronic exposure may induce intestinal accumulation and systemic toxicity, underscoring the need for regulatory thresholds to mitigate nanoplastic risks. Keywords: polystyrene nanoplastics, toxicokinetics, toxicodynamics, human health risk assessment