Manipulating Silver\nNanoparticles with Biomolecular\nCorona Secreted from Vertebrates to Improve the Loading Capacity and\nBiocompatibility

Silver nanoparticles (AgNPs) are\nwidely used as nanoagents\nin biomedical\nfields, while it is still challenging to improve their loading capacity\nand biocompatibility in microcarrier delivering systems. Herein, the\nphysicochemical properties of AgNPs were manipulated by forming biomolecular\ncorona derived from bovine serum albumin (AC), and three organisms\nat various trophic levels: <i>Chlorella sp.</i> (BC1), <i>Daphnia magna</i> (BC2), and zebrafish (BC3). Proteins were\nidentified by chemical composition analysis as the dominant components\nadsorbed on the surface of AgNPs. Proteomics indicated that AgNPs\npreferred to bind with low molecular weight (<50 kDa) and hydrophobic\nproteins with more positively charged residues. Consequently, AC and\nBC3 displayed stronger adsorption affinity on the surface of AgNPs\nthan BC1 and BC2. Modifications by AC and BC3 effectively alleviated\nthe oxidative stress and cell cycle arrest of AgNPs due to their superior\nantioxidative ability. However, BC3 with lower hydrophobicity enabled\nAgNPs to be more biocompatible than AC at subcellular level. Moreover,\nAC could significantly improve the loading capacity of AgNPs by <i>Chlorella</i> through enhancing caveolin-mediated endocytosis.\nNotably, owing to the adsorption of abundant Ca<sup>2+</sup>-binding\nproteins, BC3-AgNPs could also be internalized by microalgae via Ca<sup>2+</sup>-dependent clathrin-mediated endocytosis, which makes it\na promising approach to deliver AgNPs. The results of this study would\nprovide insights into the development of an efficient strategy to\ndeliver AgNPs based on the microalgae carrier without altering its\noriginal properties and functionality.