纳米塑料对肿瘤微环境的生物学影响

Objectives: Nanoplastics (NPLs), generated through the degradation of environmental plastics, are emerging contaminants with potential biological risks. Although recent studies have detected NPLs in human lungs and blood, their effects on human cells remain poorly understood due to the lack of standardized particles. Previous research has predominantly relied on commercially available polystyrene particles, which may contain impurities and display heterogeneity in size and shape, leading to concerns regarding reproducibility. To overcome these limitations, standardized NPLs with uniform size and shape, free from contaminants, have recently been developed by the National Institute for Environmental Studies. In this study, we aimed to investigate the effects of these standardized NPLs on immune responses and tumor progression. Methods: Standardized polypropylene (PP)-based NPLs were subjected to UV irradiation to simulate environmental weathering. The particles were then dispersed in distilled deionized water by sonication. Particle size distribution was confirmed by dynamic light scattering. THP-1 cells (a human monocytic cell line) were treated for 24 h with phorbol 12­myristate 13-acetate to differentiate them into macrophages. A549 cells (a human lung adenocarcinoma cell line) and THP-1-derived macrophages were exposed to these NPLs. Additionally, A549 cells and NPL-exposed macrophages were co-cultured using a six-well Transwell system for 48 hours. Cytotoxicity was evaluated using MTT assays, and protein expression was assessed by Western blotting. Phenotypic changes associated with EMT were evaluated by transwell migration and invasion assays. Results: NPLs were stably dispersed with an average diameter of approximately 400 nm as measured by dynamic light scattering. No significant cytotoxicity was observed in A549 cells at PP concentrations up to 250 μg/mL. Direct exposure of A549 cells to NPLs did not induce epithelial-mesenchymal transition (EMT). In contrast, THP-1-derived macrophages exposed to NPLs exhibited increased expression of CD163, suggesting polarization toward a tumor-promoting phenotype. When NPL-exposed macrophages were co-cultured with A549 cells in a Transwell system, co-cultured A549 cells displayed EMT-like features, including reduced E-cadherin and elevated vimentin expression compared to parental cells. Functionally, co-cultured A549 cells exhibited significantly enhanced migratory and invasive abilities compared to parental cells. Conclusions: This study demonstrates that PP-based NPLs can alter immune cell behavior and indirectly promote tumor progression by shaping the tumor microenvironment. We established an exposure model using standardized NPLs that reflect the intrinsic physicochemical properties of the particles.