Activating Tumor‐Selective Liquid Metal Nanomedicine through Galvanic Replacement

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.