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 H₂O₂ and acidity in tumor. Herein, an acid-sensitive nanoplatform (ZIF67-ICG/TAM@GOx) to promote H₂O₂ 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 O₂ and H₂O₂, accelerating the depletion of β-d-glucose by GOx to generate gluconate and H₂O₂. The gluconate in turn boosts the acidity to facilitate the collapse of nanoparticles, further significantly promoting the accumulation of intracellular H₂O₂ through a positive circulation. Consequently, the amplificated endogenous H₂O₂ 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 H₂O₂ and acidity deficiency simultaneously for intensive CDT, providing new prospects for the development of biocompatible cancer synergistic therapy strategies.