Abstract
AbstractSevere toxicity and rapid in vivo clearance of cationic nanomaterials seriously hinder their clinical translation. Present strategies to improve the biosafety and in vivo performance of cationic nanomaterials require neutralization of positive charge, which often compromises their efficacy. Herein, we report that substituting L‐glutathione (L‐GSH) on cationic gold nanoclusters (GNCs) with its D‐counterpart can effectively improve the biosafety and pharmacokinetics. Compared with L‐GNCs, D‐GNCs do not exhibit cellular cytotoxicity, hemolysis, or acute damage to organs. Cationic D‐GNCs show less cell internalization than L‐GNCs, and do not induce cellular apoptosis. In vivo, the chirality of surface ligands distinctly affects the pharmacokinetics and tumor targeting abilities of D‐/L‐GNCs. D‐GNCs show higher extended circulation time in blood plasma compared to similarly‐sized and poly (ethylene glycol)‐modified gold nanoparticles. This work demonstrates that the choice of chirality of surface ligands can determine toxicities and pharmacokinetics of cationic nanomaterials.
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