Tumor Microenvironment Responsive Biomimetic Copper Peroxide Nanoreactors for Drug Delivery and Enhanced Chemodynamic Therapy

Abstract Facing the multiple and arduous characteristics of tumors, chemodynamic therapy (CDT) is an emerging therapeutic approach. It uses toxic hydroxyl radical (∙OH) produced by Fenton reaction to induce cell apoptosis, which is not restricted by other factors such as the limitations of tissue depth and hypoxic tumor microenvironment. However, the problem of insufficient endogenous hydrogen peroxide (H2O2) seriously restricts its development and widespread use. In this study we developed a new type of nano-Fenton catalyst SS-CuO2@Dox (SCD), which was prepared by the peroxidation reaction of Cu2+. Under the decoration of sericin, it had excellent hydrophilicity and biocompatibility, and could target the tumor regions via the enhanced permeability and retention (EPR) effect. It could be decomposed under the acidic conditions of the tumor microenvironment (TME) and endogenously released H2O2 and Cu2+, which enhanced the efficiency of the Fenton reaction. At the same time, the successful delivery of doxorubicin (Dox), a chemotherapeutic drug, realized the combination of chemotherapy and CDT, improving the therapeutic effect of tumor. The strategy of generating H2O2 in situ could solve the problem of insufficient H2O2 in tumor without causing damage to other tissues and organs. This treatment provided a new idea for enhanced CDT and synergistic therapy, showing a promising prospect of application.