A pH−Activated Autocatalytic Nanoreactor for Self−Boosted Fenton−like Chemodynamic Therapy

The emergence of hydroxyl radical (•OH)−mediated chemodynamic therapy (CDT) by Fenton or Fenton−like reaction holds great potential for improving anticancer efficacy. Herein, an activatable autocatalytic nanoreactor (HT@GOx−DMONs) was developed for self−boosted Fenton−like CDT via decorating Cu2+−based metal−organic framework (MOF) on glucose oxidase (GOx)−loaded dendritic mesoporous organosilica nanoparticles (DMONs) for the first time. The obtained nanoreactor could prevent the premature leakage of Cu2+ and GOx in neutral physiological environments conducted by the gatekeeper of growing carboxylate MOF (HKUST−1), but the explosive release of agents could be realized due to the activated degradation of external HKUST−1 in acidic condition of endo/lysosomes, which thereby endowed this nanoreactor with the performance of pH−triggered •OH generation driven by Cu+−mediated autocatalytic Fenton−like reaction. Excitingly, Cu2+−induced glutathione (GSH) depletion and GOx−catalyzed H2O2 self−sufficiency unlocked by acid dramatically enhanced •OH generation. As expected, the effect of self−amplified CDT based on Cu2+−containing HT@GOx−DMONs presented wonderful in vitro toxicity and in vivo antitumor ability without leading to the significant side−effects. This autocatalytic Fenton−like nanoreactor with GSH consumption and self−supplying H2O2 in response to acid may provide a promising paradigm for on−demand violent CDT.