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

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