Conformational-transited protein corona regulated cell-membrane penetration and induced cytotoxicity of ultrasmall Au nanoparticles

Nanoparticles (NP) in biological fluids almost invariably become coated with proteins to form protein coronas. It is the NP-protein corona rather than the bare nanoparticle that determines the nanoparticle's bio-behavior. Here, ultrasmall gold nanoparticles (AuNPs) coated by a human serum albumin (HSA) corona were studied by Fourier transform infrared spectroscopy, denature experiments, fluorescence quenching. Moreover, the intracellular fate of AuNPs and the AuNP-HSA corona has also been investigated. The results show that HSA corona undergo a conformational transition (partial beta-sheet changed to alpha-helicity) when they adsorb on AuNPs, which lead to an enhanced thermal stability. Importantly, we observed that the conformation-transited protein corona-AuNP complex could induce cell apoptosis. Meanwhile, for the first time, the conformation-transited HSA on the AuNPs surface are shown to disrupt living cell membranes. The results obtained here not only provide the detailed conformational behavior of HSA molecules on nanoparticles, but also reveal the structure-function relationship of protein corona, which is of utmost importance in the safe application of nanoscale objects in living organisms.