GSH‐Responsive Organosilica Hybrid Nanosystem as a Cascade Promoter for Enhanced Starvation and Chemodynamic Therapy
Huan Wu, Xianglong Li, Shi Liu, Qinghua Wang, Yuanyuan Cao, Ji‐Na Hao, Yongsheng Li
Abstract
Abstract Glucose oxidase (GOD)‐mediated starvation therapy (ST) that causes intratumoral glucose depletion is a promising strategy for tumor treatment. However, the ultimate efficacy is inevitably limited by tumor hypoxia, as oxygen is a key component in the consumption of glucose by GOD. In this study, a kind of glutathione (GSH)‐responsive organosilica hybrid micelles loaded with Mn 3 O 4 and GOD (denoted as Mn 3 O 4 @PDOMs‐GOD) is ingeniously designed for enhanced ST and chemodynamic therapy (CDT). Specifically, the internalized Mn 3 O 4 @PDOMs‐GOD in tumor cells consumes intracellular glucose and oxygen (O 2 ) under the catalysis of GOD to generate hydrogen peroxide (H 2 O 2 ), which is subsequently decomposed by Mn 3 O 4 to liberate O 2 . This cyclically regenerated O 2 will form a virtuous cycle of O 2 and H 2 O 2 compensation to enhance the ST outcome. Meanwhile, Mn 3 O 4 can oxidize and deplete the overexpressed GSH in the tumor microenvironment (TME) to release Mn 2+ , which then catalyzes H 2 O 2 into highly toxic hydroxyl radicals ( · OH) to accomplish chemodynamic therapy (CDT). Both in vitro and in vivo experiment results demonstrate the significant antitumor efficacy of Mn 3 O 4 @PDOMs‐GOD by the cooperatively enhanced ST and CDT, suggesting the feasibility to develop promising therapeutic platforms with higher treatment efficacies.