A pH-activated autocatalytic nanoreactor for self-boosting Fenton-like chemodynamic therapy.

The emergence of hydroxyl radical (˙OH)-mediated chemodynamic therapy (CDT) by the Fenton or Fenton-like reaction holds great potential for improving anticancer efficacy. Herein, an activatable autocatalytic nanoreactor (HT@GOx-DMONs) was developed for self-boosting Fenton-like CDT via decorating Cu-based metal-organic frameworks (MOFs) on glucose oxidase (GOx)-loaded dendritic mesoporous organosilica nanoparticles (DMONs) for the first time. The obtained nanoreactor could prevent the premature leakage of Cu and GOx in neutral physiological environments conducted by the gatekeeper of growing carboxylate MOF (HKUST-1), but the explosive release of agents was 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, Cu-induced glutathione (GSH) depletion and GOx-catalyzed HO self-sufficiency unlocked by acid dramatically enhanced ˙OH generation. As expected, the effect of self-amplified CDT based on Cu-containing HT@GOx-DMONs presented wonderful in vitro toxicity and in vivo antitumor ability without leading to significant side-effects. The resulting nanoreactor with GSH consumption and HO self-supply activated by acid may provide a promising paradigm for on-demand CDT.