Synchronous Interference of Dual Metabolic Pathways Mediated by H 2 S Gas/GOx for Augmenting Tumor Microwave Thermal Therapy

作者：Shimei Li, Qiong Wu, Zengzhen Chen, Wenna Guo, Longfei Tan, Xiangling Ren, Changhui Fu, Guihua Jiang, Zhongbing Huang, Xianwei Meng · 发表于：ACS Applied Materials & Interfaces · 年份：2025 · DOI：10.1021/acsami.4c18641 · 被引用次数：7 · 研究领域：Nanoplatforms for cancer theranostics、Sulfur Compounds in Biology、Cancer, Hypoxia, and Metabolism

Sublethal tumor cells have an urgent need for energy, making it common for them to switch metabolic phenotypes between glycolysis and oxidative phosphorylation (OXPHOS) for compensatory energy supply; thus, the synchronous interference of dual metabolic pathways for limiting energy level is essential in inhibiting sublethal tumor growth. Herein, a multifunctional nanoplatform of Co-MOF-loaded anethole trithione (ADT) and myristyl alcohol (MA), modified with GOx and hyaluronic acid (HA) was developed, namely, CAMGH. It could synchronously interfere with dual metabolic pathways including glycolysis and OXPHOS to restrict the adenosine triphosphate (ATP) supply, achieving the inhibition to sublethal tumors after microwave (MW) thermal therapy. Under low-power MW irradiation, CAMGH induced certain tumor thermal damage while ensuring the safety of the surrounding normal tissues. The loaded GOx consumed glucose in tumors, undoubtedly blocking the main energy supply pathway, the glycolytic pathway. Then, H 2 O 2 generated from GOx reacted with Co 2+ to produce cytotoxic ·OH, combining with the released H 2 S from ADT to co-obstruct OXPHOS and then synergy with the above glycolysis blocking for a more effective ATP inhibition. The powerful depletion of ATP caused significant suppression of damage resistance protein upregulated after thermal stimulation, i.e., HSP90, and then the activation of caspase-3, achieving the simultaneous reversal of heat resistance and apoptosis resistance. ...