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 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 Cu2+ ions and producing Ga3+ 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(NO3)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