Manganese(II)‐Guided Separation in the Sub‐Nanometer Regime for Precise Identification of In Vivo Size Dependence

Abstract

AbstractA precise understanding of nano‐bio interactions in the sub‐nanometer regime is necessary for advancements in nanomedicine. However, this is currently hindered by the control of the nanoparticle size in the sub‐nanometer regime. Herein, we report a facile in situ Mn2+‐guided centrifugation strategy for the synthesis of large‐scale ultrasmall gold nanoparticles (AuNPs) with a precisely controlled size gradient at the sub‐nanometer regime. With the discovery that [Mn(OH)]+, especially metallic manganese (Mn0@[Mn(OH)]+) nanoparticles, could selectively interact with larger AuNPs through synergistic coordination and hydrogen bonding to form aggregates, we also realized the fast (<1 h) synthesis of water‐soluble atomically precise Au25 with high yields (>56 %). We further demonstrated that sub‐nanometer size differences (approximately 0.5 nm) significantly alter non‐specific phagocytosis of AuNPs in the reticuloendothelial system macrophages, elimination rate, and nanotoxicology.