A FeO/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 therapy (CDT), photodynamic therapy (PDT), and their combination, are effective for treating cancer. Developing a nanoreactor with combined functions of catalase (CAT) and peroxidase (POD) that can simultaneously convert excess HO in tumors into O required for type II PDT and hydroxyl radicals (•OH) for CDT can help achieve combined therapy. Here, we reported on a safe FeO/CNx nanoreactor with dual enzyme simulated activity, in which CNx sheet was the carrier and reducing agent to convert FeO to Fe. After modified by MgO and photosensitizer Ce6, MgO-FeO/CNx-Ce6 (MFCC) platform integrated multiple functions, including photosensitizer delivery, compensated HO 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.