Activating Tumor‐Selective Liquid Metal Nanomedicine through Galvanic Replacement
Junjie Yan, Jinqiang Wang, Xinyu Wang, Donghui Pan, Su Chen, Junxia Wang, Mengzhen Wang, Jianjun Xiong, Yu Chen, Lizhen Wang, Yuping Xu, Chongyang Chen, Min Yang, Zhen Gu
Abstract
Abstract Advanced chemotherapeutic strategies including prodrug and nanocatalytic medicine have significantly advanced tumor‐selective theranostics, but delicate prodrug screening, tedious synthesis, low degradability/biocompatibility of inorganic components, and unsatisfied reaction activity complicate treatment efficacies. Here, the intrinsic anticancer bioactivity of liquid metal nanodroplets (LMNDs) is explored through galvanic replacement. By utilizing a mechano‐degradable ligand, the resultant size of the aqueous LMND is unexpectedly controlled as small as ≈20 nm (LMND20). It is demonstrated that LMND20 presents excellent tumor penetration and biocompatibility and activates tumor‐selective carrier‐to‐drug conversion, synchronously depleting Cu 2+ ions and producing Ga 3+ ions through galvanic replacement. Together with abundant generation of reactive oxygen species, multiple anticancer pathways lead to selective apoptosis and anti‐angiogenesis of breast cancer cells. Compared to the preclinical/clinical anticancer drugs of tetrathiomolybdate and Ga(NO 3 ) 3 , LMND20 administration significantly improves the therapeutic efficacy and survival in a BCap‐37 xenograft mouse model, yet without obvious side effects.