Identification and interaction mechanism of protein corona on silver nanoparticles with different sizes and the cellular responses

With the potential biomedical applications of nanomaterials such as silver nanoparticles (SNPs), nanotoxicity concerns are growing, and the importance of NP and protein interactions is far from being addressed enough. Here, we identified the major binding protein on SNPs in blood as human serum albumin (HSA) using polyacrylamide gel electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry. By comparing with the previous methods, we emphasized surface area concentration as a new dose metric to address the importance of NP curvature. SNPs interacted with cysteine and cystine, disrupting the secondary structure and conformation of HSA, and this tendency became stronger on small SNPs than large ones. The protein corona significantly alleviated the toxicity and decreased SNPs' internalization in a particle size-dependent manner, where more significant inhibition effects occurred on larger particles at the same area concentration. These findings may shed light on nanotoxicity and also the design of safe nanomaterials by a comprehensive preconsideration of the metrological method.