Contribution\nof Cancer-Specific Protein Coronas to\nthe Pro-Tumor Effects of Nanoplastics through Enhanced Cellular Interactions

The\npotential impact of nanoplastics (NPs) on human carcinogenic\nprocesses is a matter of growing concern, particularly in light of\nthe global plastic pollution crisis. Although the potential effects\nof NPs on human health have been well investigated, many uncertainties\n remain regarding their role in tumor behavior. Upon exposure, NPs\ncan enter the bloodstream and are prone to interacting with plasma\nproteins to form a protein corona (PC), which can influence their\ninteractions with cancer cells. However, how the PCs adsorbed on NPs\naffect the particle-to-tumor cell interaction and their effect on\nthe tumor biological behavior remain unclear. To better understand\nthe formation of PCs following NPs exposure in the bloodstream under\nvarious clinical conditions, we investigated the PC compositions of\nNPs derived from thyroid cancer (TC) patients and healthy volunteers.\nOur data revealed a significant enrichment of fibrinogen in the PCs\nformed on NPs derived from TC patient plasma, which in turn accelerated\nthe endocytosis of NPs into TC cells. In addition, the uptake pathway\nof NPs into TC cells differed substantially between the two groups\nstudied due to the different PC compositions in cancer patients and\nhealthy individuals. Moreover, intriguingly alterations in the PCs\ninduced by the clinical pathology status were also found to promote\nNPs engulfment by human macrophages, resulting in potent pro-inflammatory\neffects, in turn exerting pro-tumor effects. These findings emphasize\nthe importance of considering the significance of a realistic biological\nidentity on NPs and their interactions with cancer cells and also\npinpoint the implications of the carcinogenesis outcomes of NPs exposure\nin humans.