Enhanced Bacterial Cuproptosis‐Like Death via Reversal of Hypoxia Microenvironment for Biofilm Infection Treatment

作者：Zhiyuan Luo, Renjie Lu, Tingwang Shi, Zesong Ruan, Wenbo Wang, Zhaojiang Guo, Zeming Zhan, Yihong Ma, Xiaofeng Lian, Cheng Ding, Yunfeng Chen · 发表于：Advanced Science · 年份：2024 · DOI：10.1002/advs.202308850 · 被引用次数：48 · 研究领域：Nanoplatforms for cancer theranostics、Advanced Nanomaterials in Catalysis、Autophagy in Disease and Therapy

Abstract A recently emerging cell death pathway, known as copper‐induced cell death, has demonstrated significant potential for treating infections. Existing research suggests that cells utilizing aerobic respiration, as opposed to those reliant on glycolysis, exhibit greater sensitivity to copper‐induced death. Herein, a MnO 2 ‐loaded copper metal–organic frameworks platform is developed denoted as MCM, to enhance bacterial cuproptosis‐like death via the remodeling of bacterial respiratory metabolism. The reversal of hypoxic microenvironments induced a cascade of responses, encompassing the reactivation of suppressed immune responses and the promotion of osteogenesis and angiogenesis. Initially, MCM catalyzed O 2 production, alleviating hypoxia within the biofilm and inducing a transition in bacterial respiration mode from glycolysis to aerobic respiration. Subsequently, the sensitized bacteria, characterized by enhanced tricarboxylic acid cycle activity, underwent cuproptosis‐like death owing to increased copper concentrations and aggregated intracellular dihydrolipoamide S‐acetyltransferase (DLAT). The disruption of hypoxia also stimulated suppressed dendritic cells and macrophages, thereby strengthening their antimicrobial activity through chemotaxis and phagocytosis. Moreover, the nutritional effects of copper elements, coupled with hypoxia alleviation, synergistically facilitated the regeneration of bones and blood vessels. Overall, reshaping the infection microenvironm...