Missing‐Linker‐Assisted Artesunate Delivery by Metal–Organic Frameworks for Synergistic Cancer Treatment

Abstract

AbstractClinical translation of artesunate (ATS) as a potent antitumor drug has been obstructed by its rapid degradation and low bioavailability. Herein, we report the development of an ATS nanomedicine through the self‐assembly with Mn[Co(CN)6]2/3□1/3 metal–organic frameworks (MOFs) that have hidden missing linkers. The defects in MOFs originating from the missing linkers play a key role in increasing the biological stability and tumor accumulation of ATS. Chlorin e6 (Ce6) and ATS can be co‐loaded into MOFs for a synergistic antitumor efficacy. In the presence of intracellular HCO3−, Mn2+ acts as an efficient catalyst to promote the bicarbonate‐activated H2O2 system which oxidizes ATS to generate reactive oxygen species and induce oxidative death to cancer cells. The released [CoIII(CN)6] linker undergoes a redox reaction with intracellular glutathione to prevent the scavenging ability of reactive oxygen species, contributing to synergistic chemodynamic therapy of ATS and photodynamic therapy of Ce6. Thus, defect‐engineered MOFs with hidden missing linkers hold great promise in advancing the practical use of ATS as an antitumor medicine.