Biocatalysis of MnO2-Mediated Nanosystem for Enhanced Multimodal Therapy and Real-Time Tracking

Clearance of endogenous glutathione (GSH) to cytotoxic hydroxyl radicals (•OH) and insufficient cellular hydrogen peroxide (H2O2) limited the efficacy of chemodynamic therapy (CDT) to a tumor. Herein, a biocompatible nanosystem has been developed to overcome the dilemma of CDT; first, soya lecithin, paclitaxel, MnO2 nanoparticles, and glucose oxidase (GOx) were self-assembled to PTX/MnO2/GOx-Lips and then hyaluronic acid (HA) was modified on the surface of nanosystem to enhance tumor targeting. MnO2 consumed the endogenous GSH to generate Mn2+, which relieved the clearance of •OH and enhanced the CDT effect; meanwhile, Mn2+-mediated magnetic resonance imaging (MRI) also can provide the track of prepared nanosystem in vivo synchronously. Furthermore, the O2 generated from the CDT process promoted starving-like therapy, which, in turn, provided more H2O2 for intensifying CDT. The final tumor inhibition effect was nearly 93.92% in tumor-bearing mice. Therefore, our design solved the long-standing limitation of CDT and showed excellent antitumor efficacy, which also achieved the highly efficient synergy of CDT, starving-like therapy, chemotherapy, and real-time tracking. The study makes a great contribution to the development of CDT, even in the field of cancer treatment, which exhibits potential for clinic transformation.