Enhanced Macrophage Internalization of Photoaged Nanoplastics Mediated by Altered Serum Albumin Secondary Structure

After nanoplastics (NPs) experience photoaging in an aquatic environment, they may enter blood circulation of organisms and interact with proteins, which significantly affect their cellular uptake and biological effects. In this study, polystyrene nanoplastics (PSNPs) and human serum albumin (HSA) were chosen as representative models of NPs and proteins, respectively. The photoaged PSNPs exhibited decreased particle size and increased surface oxidation, which not only promoted their binding with HSA but also led to preferential binding with the α-helix regions of HSA. Consequently, the α-helical content of the adsorbed HSA molecules on photoaged PSNPs decreased significantly, leading to a denaturation effect comparable to thermal treatment. Dissolved substances released from PSNPs had a negligible impact on HSA's conformation. The denatured HSA activated additional endocytic pathways, notably enhancing SR-A1-mediated endocytosis of mouse monocyte macrophages (RAW 264.7), which thus promoted the cellular uptake of the photoaged PSNPs compared with pristine ones. This study suggests that photoaging may greatly alter the interactions of NPs with proteins, thereby influencing cellular uptake mechanisms, and then alter their potential biodistribution and biological effects <i>in vivo</i>.