Cell uptake of mixtures of different-sized nanoplastics: Interplay and mechanism

Nanoplastics in the real world always exhibit a wide size distribution. Is the endocytosis mechanism of mixed-sized nanoplastics different from that of single-sized ones? To answer this fundamental question, herein, the cellular uptake of polystyrene nanoplastics of 50 nm (G50PS, 2.5-10 μg/mL) and 100 nm (R100PS, 10-60 μg/mL), with a number ratio range of 0.5:1-12:1, was investigated under co-exposure conditions. The results show that, compared to single exposure, the cellular uptake of G50PS is generally enhanced (by up to 74.2 %) by R100PS, because R100PS can easily trigger the clathrin-mediated endocytosis, bringing nearby G50PS into cells. The effect of G50PS on the uptake of R100PS is more complicated, especially in serum-containing medium, both enhancement (up to 71.3 %) and inhibition (up to 38.2 %) by G50PS are observed, depending on the mixing conditions. A mechanism involving protein coronas is proposed to explain the endocytic behaviors of R100PS in serum-containing medium: the competition of G50PS for the limited preferred serum proteins changes the protein corona of R100PS, thereby altering its uptake depending on the concentration and ratio of G50PS and R100PS. This finding reveals the complex nature of nanoplastics-bio interactions and sheds light on the evaluation of nanoplastic toxicity.