Biocatalysis of MnO<sub>2</sub>-Mediated Nanosystem for Enhanced Multimodal Therapy and Real-Time Tracking
Xiaowei Li, Xiaoyu Zhang, Xiaoyu Zhang, Weidong Zhang, Lei Li, Wenbin Gao, Xuwu Zhang, Xuwu Zhang, Dawei Gao
Abstract
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.