Alloying Impacts <i>In Vivo</i> Behaviors of Ultrasmall Noble-Metal Nanoparticles through Intermetallic Charge-Transfer Mediated Ligand-Core Interactions.

Abstract

Noble-metal nanoparticles (NMNPs) show great promise for their biomedical use. While it is known that surface ligands vastly impact their biological fate <i>in vivo</i>, the influence of ligand-core interactions remains underexplored. Herein, we showed that ultrasmall mercaptosuccinic acid (MSA)-coated gold/platinum (Au/Pt) alloy nanoparticles exhibited distinct <i>in vivo</i> targeting and clearance behaviors compared to their monometallic analogs, despite having identical surface ligands. Mechanistic studies revealed much stronger noncovalent ligand-core interactions in the alloy nanoparticles relative to the monometallic nanoparticles, due to intermetallic charge-transfer of the alloyed core. This enhanced ligand-core interaction further attenuated nanoparticle surface charge, leading to reduced serum protein adsorption and recognition by the mononuclear phagocyte system and eventually resulting in distinct <i>in vivo</i> behaviors. Our findings thus highlight the ligand-core interactions in regulating biological behaviors of NMNPs through affecting nanoparticle surface charge and protein adsorption, suggesting core composition as a tunable parameter for modulating the nano-bio interactions.