A Nano‐Autophagy Inhibitor Triggering Reciprocal Feedback Control of Cholesterol Depletion for Solid Tumor Therapy

• DOI: 10.1002/adhm.202302020
• Publication Date: 2023-09-28T12:38:51Z
• Authors: Pengfei Zhang; Yanfeng Shi; Yuanhong Xu; Ye Liang; Chao Huang; Di Zhong; Zhilei Zhang; Yongbo Yu; Zhao Zhang; Jianfeng Zhang; Lei Yu; Yuhui Zuo; Xinsheng Wang; Haitao Niu
• Keywords: Cholesterol Oxidase

Abstract Solid tumors are characterized by enhanced metabolism of lipid, particularly cholesterol, inspiring the exploration metabolic therapy through cholesterol oxidase (COD)‐mediated deprivation. However, therapeutic efficacy COD is limited due to hypoxic tumor microenvironment and protective autophagy triggered Herein, a combination for metabolically treating solid in conjunction with molybdenum oxide nanodots (MONDs), which serve as both potent oxygen generators inhibitors, reported. MONDs convert H 2 O (arising from COD‐mediated oxidation) into , then recycled form reciprocal feedback depletion. Concurrently, can overcome autophagy‐induced resistance frequently occurring conventional nutrient deprivation activating AKT/mTOR pathway phosphorylation. Combination xenograft model results an ≈5‐fold increase efficiency compared treatment alone. This functionally cooperative coupling strategy holds great promise novel polytherapy approach that will benefit patients tumors.