Activating Tumor-Selective Liquid Metal Nanomedicine through Galvanic Replacement.

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 we explore intrinsic anticancer bioactivity of liquid metal nanodroplet (LMND) through the galvanic replacement. By utilizing a mechano-degradable ligand, the resultant size of aqueous LMND is unexpectedly controlled as small as ∼20 nm (LMND20). We demonstrate 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 the 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. This article is protected by copyright. All rights reserved.