Manipulating Silver Nanoparticles with Biomolecular Corona Secreted from Vertebrates to Improve the Loading Capacity and Biocompatibility

Silver nanoparticles (AgNPs) are widely used as nanoagents in biomedical fields, while it is still challenging to improve their loading capacity and biocompatibility in microcarrier delivering systems. Herein, the physicochemical properties of AgNPs were manipulated by forming biomolecular corona derived from bovine serum albumin (AC), and three organisms at various trophic levels: <i>Chlorella sp.</i> (BC1), <i>Daphnia magna</i> (BC2), and zebrafish (BC3). Proteins were identified by chemical composition analysis as the dominant components adsorbed on the surface of AgNPs. Proteomics indicated that AgNPs preferred to bind with low molecular weight (<50 kDa) and hydrophobic proteins with more positively charged residues. Consequently, AC and BC3 displayed stronger adsorption affinity on the surface of AgNPs than BC1 and BC2. Modifications by AC and BC3 effectively alleviated the oxidative stress and cell cycle arrest of AgNPs due to their superior antioxidative ability. However, BC3 with lower hydrophobicity enabled AgNPs to be more biocompatible than AC at subcellular level. Moreover, AC could significantly improve the loading capacity of AgNPs by <i>Chlorella</i> through enhancing caveolin-mediated endocytosis. Notably, owing to the adsorption of abundant Ca²⁺-binding proteins, BC3-AgNPs could also be internalized by microalgae via Ca²⁺-dependent clathrin-mediated endocytosis, which makes it a promising approach to deliver AgNPs. The results of this study would provide insights into the development of an efficient strategy to deliver AgNPs based on the microalgae carrier without altering its original properties and functionality.