Multifunctional CuFeO@HA as a GSH-depleting nanoplatform for targeted photothermal/enhanced-chemodynamic synergistic therapy.

Chemodynamic therapy (CDT), which converts overexpressed hydrogen peroxide (HO) in tumor cells to hydroxyl radicals (•OH) by Fenton reactions, is considered a prospective strategy in anticancer therapy. However, the high level of glutathione (GSH) and poor Fenton catalytic efficiency contribute to the suboptimal efficiency of CDT. Herein, we present a multifunctional nanoplatform (CuFeO@HA) that can induce GSH depletion and combine with photothermal therapy (PTT) to enhance antitumor efficacy. CuFeO@HA nanoparticles could release Cu and Fe after entering tumor cells by targeting hyaluronic acid (HA). Subsequently, Cu and Fe were reduced to Cu and Fe by GSH, where Cu/Fe significantly catalyzed HO to produce a higher level of •OH, and the depletion of GSH disrupted the antioxidant capacity of the tumor. Therefore, depleting GSH substantially enhances the level of •OH in tumor cells. In addition, CuFeO@HA nanoparticles have considerable absorption in the near-infrared (NIR) region, which can stimulate excellent PTT effects. More importantly, the heat generated by PTT can further enhance the Fenton catalysis efficiency. In vitro and in vivo experiments have demonstrated the excellent tumor-killing effect of CuFeO@HA nanoparticles. This strategy overcomes the problem of insufficient CDT efficacy caused by GSH overexpression and poor catalytic efficiency. Moreover, this versatile nanoplatform provides a reference for self-enhanced CDT and PTT/CDT synergistic targeted therapy.