Hexahistidine-metal assemblies: A promising drug delivery system.

It is of considerable interest to construct an ideal drug delivery system (i.e., high drug payload, minimal cytotoxicity, rapid endocytosis, and lysosomal escape) under mild conditions for disease treatment, tissue engineering, bioimaging, etc. Inspired by the coordinative interactions between histidine and metal ions, we present the facile synthesis of hexahistidine (His6)-metal assembly (HmA) particles under mild conditions for the first time. The HmA particles presented a high loading capacity, a wide variety of loadable drugs, minimal cytotoxicity, quick internalization, the ability to bypass the lysosomes, and rapid intracellular drug release. In addition, HmA encapsulation largely improved the antitumor ability of camptothecin (CPT) relative to free CPT. By capitalizing on these promising features in drug delivery, HmA will have great potential in various biomedical fields. STATEMENT OF SIGNIFICANCE: It is of considerable interest to construct an ideal drug delivery system (i.e., high drug payload, minimal cytotoxicity, rapid endocytosis, and lysosomal escape) under mild conditions. Inspired by the coordinative interactions between histidine and metal ions, we present for the first time the facile synthesis of Hexahistidine (His6)-metal assembly (HmA) particles under mild conditions. The HmA particles exhibited a high loading capacity, a wide variety of loadable drugs, minimal cytotoxicity, quick internalization, the ability to bypass the lysosomes, and rapid intracellular drug release. By capitalizing on these promising features in drug delivery, HmA will have great potential in various biomedical fields.