H₂O₂ Self-Supplying and GSH-Depleting Nanoplatform for Chemodynamic Therapy Synergetic Photothermal/Chemotherapy

Abstract

Chemodynamic therapy (CDT) that utilizes Fenton-type reactions to convert endogenous hydrogen peroxide (H₂O₂) into hydroxyl radicals (^•OH) is a promising strategy in anticancer treatment, but the overexpression of glutathione (GSH) and limited endogenous H₂O₂ make the efficiency of CDT unsatisfactory. Here, an intelligent nanoplatform CuO₂@mPDA/DOX-HA (CPPDH), which induced the depletion of GSH and the self-supply of H₂O₂, was proposed. When CPPDH entered tumor cells through the targeting effect of hyaluronic acid (HA), a release of Cu²⁺ and produced H₂O₂ were triggered by the acidic environment of lysosomes. Then, the Cu²⁺ was reduced by GSH to Cu⁺, and the Cu⁺ catalyzed H₂O₂ to produce ^•OH. The generation of ^•OH could be distinctly enhanced by the GSH depletion and H₂O₂ 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 H₂O₂ and overexpression of GSH. This multifunctional nanoplatform may open a broad path for self-boosting CDT and synergistic therapy.