HO Self-Supplying and GSH-Depleting Nanoplatform for Chemodynamic Therapy Synergetic Photothermal/Chemotherapy.

Chemodynamic therapy (CDT) that utilizes Fenton-type reactions to convert endogenous hydrogen peroxide (HO) into hydroxyl radicals (OH) is a promising strategy in anticancer treatment, but the overexpression of glutathione (GSH) and limited endogenous HO make the efficiency of CDT unsatisfactory. Here, an intelligent nanoplatform CuO@mPDA/DOX-HA (CPPDH), which induced the depletion of GSH and the self-supply of HO, was proposed. When CPPDH entered tumor cells through the targeting effect of hyaluronic acid (HA), a release of Cu and produced HO were triggered by the acidic environment of lysosomes. Then, the Cu was reduced by GSH to Cu, and the Cu catalyzed HO to produce OH. The generation of OH could be distinctly enhanced by the GSH depletion and HO self-sufficiency. Besides, an outstanding photothermal therapy (PTT) effect could be stimulated by NIR irradiation on mesoporous polydopamine (mPDA). Meanwhile, mPDA was an excellent photoacoustic reagent, which could monitor the delivery of nanocomposite materials through photoacoustic (PA) imaging. Moreover, the successful delivery of doxorubicin (DOX) realized the integration of chemotherapy, PTT, and CDT. This strategy could solve the problem of insufficient CDT efficacy caused by the limited HO and overexpression of GSH. This multifunctional nanoplatform may open a broad path for self-boosting CDT and synergistic therapy.