Fe2o3/Cnx Cascade Nanoreactor with Dual-Enzyme-Mimetic Activities for Cancer Hypoxia Relief to Amplify Chemo/Photodynamic Therapy

Reactive oxygen species (ROS) mediated therapeutic strategies, including chemodynamic (CDT) and photodynamic (PDT) therapies, especially their combination, are effective for treating cancer. Developing a nanoreactor with combined functions of catalase (CAT) and peroxidase (POD) that can simultaneously convert excess H2O2 in tumors into O2 required for type II PDT and hydroxyl radicals (•OH) for CDT, which can help achieve combined therapy. Herein, we report on a safe Fe2O3/CNx nanoreactor with dual enzyme simulated activity, in which CNx sheet is found for the first time as the carrier and reducing agent to convert Fe2O3 to Fe2+. After modified by MgO2 and photosensitizer Ce6, MgO2-Fe2O3/CNx-Ce6 (MFCC) platform integrated multiple functions, including photosensitizer delivery, compensated H2O2 continuous supply, relieve of hypoxia, generation of •OH and consumption of GSH into a single formulation. Under 660 nm irradiation for 4 min, MFCC actives more ROS to conduct PDT/CDT, leading to the remarkable reduced survival rate of breast cancer cells to 14%. Due to the enhanced permeability and retention (EPR) effect, MFCC can retain and accumulate at the tumor site of mice for a longer period that inhibit the expression of tumor angiogenic factors, suppress tumor neovascularization, and suppress the proliferation and growth of tumor cells.