Alloying Impacts In Vivo Behaviors of Ultrasmall Noble-Metal Nanoparticles through Intermetallic Charge-Transfer Mediated Ligand-Core Interactions

Noble-metal nanoparticles (NMNPs) show great promise for their biomedical use. While it is known that surface ligands vastly impact their biological fate in vivo, 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 in vivo 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 in vivo 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.