GSH-Responsive Metal–Organic Framework-Based Nanoplatform for Combined Chemo–Chemodynamic Therapy
Sucheta Chatterjee, Archita Rai, Raghavendra S. Patwardhan, Ruchi Agrawal, Pallavi Chandwadkar, Debojyoti Pal, Sudip Gorai, Celin Acharya, Anand Ballal, Santosh K. Sandur, Dibakar Goswami
Abstract
Efficient chemodynamic therapy requires the intracellular self-supply of H 2 O 2 with the simultaneous depletion of glutathione (GSH). The anticancer drug doxorubicin (DOX) was loaded onto CaO 2 nanoparticles followed by encapsulation of CaO 2 -DOX into a Cu-based metal–organic framework (CuMOF), which was surface modified with poly(ethylene)glycol (PEG) to form the CaO 2 -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 CaO 2 -DOX-CuMOF/PEG to release DOX and CaO 2, promoting the formation of H 2 O 2 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.