Impact of an Artificial Albumin Corona on Surface Charge-Driven Nano-Bio Interactions and Cytotoxicity of Silver Nanoparticles.

The clinical translation of nanomedicine remains limited by the low and often unpredictable delivery efficiency of nanoparticles, largely arising from protein corona formation and its complex interplay with nanoparticle surface properties. In this context, strategies based on engineered protein coronas have emerged to improve control over nano-bio interactions. In this work, we investigate the interplay between an artificial protein corona formed using bovine serum albumin (BSA), the most abundant serum protein, and surface charge, one of the key determinants of interactions at the nano-bio interface, in shaping the biological behavior of silver nanoparticles (AgNPs). Negatively charged citrate-stabilized AgNPs and positively charged PAH-coated AgNPs were precoated with BSA and evaluated across three cell lines selected for their different sensitivities to nanoparticle surface charge. Our results show that BSA precoating markedly enhances nanoparticle stability in complex media, particularly for positively charged AgNPs, yet does not significantly alter the qualitative composition of the adsorbed protein corona or the cytotoxic responses elicited by the nanoparticles. Under serum-free conditions, however, BSA coating becomes essential for maintaining colloidal stability and enabling cellular interactions, thereby allowing AgNPs to exert their intrinsic biological activity. These findings demonstrate that although the artificial corona provides important colloidal stabilization, surface charge remains the dominant factor governing the biological behavior of AgNPs, further highlighting the need to elucidate the mechanisms underlying charge-dependent interactions at the nano-bio interface for the rational engineering of nanoparticle systems.