Glutathione-Responsive Biodegradable Core–Shell Nanoparticles That Self-Generate H2O2 and Deliver Doxorubicin for Chemo–Chemodynamic Therapy.

As a kind of reactive oxygen species (ROS)-mediated cancer therapy modality, chemodynamic therapy (CDT) has been extensively explored. However, the insufficient endogenous H₂O₂ and the intracellular redox homeostasis greatly obstruct the anticancer efficacy. Developing multifunctional nanomedicine which can address these issues is appealing. Herein, 4T1 cancer cell membrane (CM)-coated glutathione (GSH)-responsive biodegradable biomimetic nanoreactor, CaO₂@MnO₂–DOX@CM, was fabricated for tumor oxidative stress amplification enhanced self-supplying H₂O₂ chemodynamic therapy and synergistic chemotherapy. Highly expressed GSH in the tumor cells could trigger the biodegradation of CaO₂@MnO₂–DOX@CM, and the Fenton-like catalyst Mn²⁺ and chemotherapy drug doxorubicin (DOX) were released. The unprotected CaO₂ further reacted with water to generate a large amount of H₂O₂ and Ca²⁺. The self-supplying H₂O₂ not only reacted with Mn²⁺ to generate hydroxyl radical (^•OH) but also sped up the biodegradation of the nanoreactor. Furthermore, the MnO₂-mediated GSH depletion and the Ca²⁺-overloading-induced mitochondria dysfunction could further enhance the CDT efficiency. Thus, the glutathione-responsive biodegradable core–shell nanoparticles achieved MRI-guided synergistic chemo–chemodynamic therapy, showing bright prospect for highly efficient tumor treatment. [ABSTRACT FROM AUTHOR]