GSH-Responsive Metal–Organic Framework-Based Nanoplatform for Combined Chemo–Chemodynamic Therapy

Abstract

Efficient chemodynamic therapy requires the intracellular self-supply of H2O2 with the simultaneous depletion of glutathione (GSH). The anticancer drug doxorubicin (DOX) was loaded onto CaO2 nanoparticles followed by encapsulation of CaO2-DOX into a Cu-based metal–organic framework (CuMOF), which was surface modified with poly(ethylene)glycol (PEG) to form the CaO2-DOX-CuMOF/PEG nanoplatform. This preparation functioned as a GSH-responsive, self-sufficient chemo–chemodynamic anticancer agent, which simultaneously generated oxidative stress endogenously and released DOX. GSH-rich cancer cells disintegrated CaO2-DOX-CuMOF/PEG to release DOX and CaO2, promoting the formation of H2O2 and thus favoring the generation of reactive oxygen species (ROS). Its antiproliferative properties were evaluated in vitro in lung adenocarcinoma cells by conducting studies on cytotoxicity, intracellular ROS generation, and mitochondrial membrane potential. In the in vivo mice tumor model, the combined chemo–chemodynamic therapy with the synthesized nanocomposite was superior in suppressing tumors than the individual therapies. Thus, this class of MOF nanoplatforms, which has the potential to be assigned with various drugs, can prove to be a valuable tool in cancer therapy.