Tumor hypoxia-responsive size-switchable nanosystems for precise delivery of
drug into deep
tumor show great prospects for killing
cancer cells with high specificity and minimal invasiveness. However, the development of versatile nanosystems is still a challenge. Herein, for the first time, we report a novel
hypoxia-responsive
copper metal-organic framework nanoparticles (Cu-MOF NPs) for chemodynamic
therapy and sonodynamic
therapy (CDT/SDT). The large size Cu-MOF NPs show good stability under normal
oxygen partial pressure and enhance
tumor accumulation, and it quickly degraded and released Cu2+ and Ce6 when exposed to the hypoxic tumor microenvironment (TME), significantly reinforced the intratumoral penetration. The internalized Cu2+ reacts with local GSH to deplete GSH and reduce Cu2+ to Cu+, which subsequently reacts with endogenous H2O2 to produce cytotoxic
hydroxyl radicals (•OH) through Fenton-like reaction for CDT. The released Ce6 further mediated SDT under US irradiation. The synergistic SDT/CDT efficacy was significantly enhanced owing to the GSH depletion, realizing selective and effective MCF-7 killing with minimal invasiveness. This work presents a novel
hypoxia-responsive MOF nanosystem with intrinsic CDT properties, mainly, the MOF nanosystem is flexible to the integration with other
therapy approaches. It provides a general strategy to design a
hypoxia-responsive MOF nano
theranostic platform.