A positive self-amplified H2O2 and acidity circulation for boosting CDT-PTT-starvation therapy.

The therapeutic application of chemodynamic therapy (CDT) is severely limited by the insufficient intracellular H 2 O 2 and acidity in tumor. Herein, an acid-sensitive nanoplatform (ZIF67-ICG/TAM@GOx) to promote H 2 O 2 and acidity enhancement through intracellular cyclic amplification for enhanced CDT is rationally designed. Notably, the acidic conditions of the tumor microenvironment (TME) can turn on the switch of the nanoplatform, setting free the loaded tamoxifen (TAM) and indocyanine green (ICG). The mitochondrial respiration inhibitor TAM and the superoxide dismutase-mimicking ZIF67 synergistically lead to an increase in the content of O 2 and H 2 O 2 , accelerating the depletion of β- d -glucose by GOx to generate gluconate and H 2 O 2. The gluconate in turn boosts the acidity to facilitate the collapse of nanoparticles, further significantly promoting the accumulation of intracellular H 2 O 2 through a positive circulation. Consequently, the amplificated endogenous H 2 O 2 is catalyzed by Co2+ to liberate hydroxyl radicals (•OH). Besides, ICG-mediated photothermal therapy (PTT) and GOx-induced starvation therapy along with CDT realize the synergistic cancer treatment. Importantly, in vitro and in vivo experiments verified that the nanoplatform performed superior specificity and excellent therapeutic responses. The smart nanoplatform overcomes H 2 O 2 and acidity deficiency simultaneously for intensive CDT, providing new prospects for the development of biocompatible cancer synergistic therapy strategies. In the tumor microenvironment, the released TAM, GOx and ZIF67 synergistically lead to a positive circulation for self-amplified CDT, cooperating with PTT and starvation to realize the synergistic cancer treatment. [Display omitted] • An acidic sensitive nanoplatform (ZIF67-ICG/TAM@GOx) is constructed for specific tumor therapy. • The combination of TAM, ZIF67 and GOx enabled positive circulation to accumulate H 2 O 2 and acidity for boosting CDT. • The disruption of H 2 O 2 homeostasis made the approach of "expanding source and cost-saving" for the increase of H 2 O 2. • The self-amplified CDT along with PTT, GOx-induced starvation realized a novel synergistic cancer therapy strategy. [ABSTRACT FROM AUTHOR]