Biofilm Microenvironment-Responsive Self-Assembly Nanoreactors for All-Stage Biofilm Associated Infection through Bacterial Cuproptosis-like Death and Macrophage Re-Rousing,Advanced Materials

当前位置： X-MOL 学术 › Adv. Mater. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Biofilm Microenvironment-Responsive Self-Assembly Nanoreactors for All-Stage Biofilm Associated Infection through Bacterial Cuproptosis-like Death and Macrophage Re-Rousing
Advanced Materials ( IF 27.4 ) Pub Date : 2023-06-01 , DOI: 10.1002/adma.202303432
Jiawei Mei ₁ , Dongdong Xu ₂ , Lingtian Wang ₂ , Lingtong Kong ₃ , Quan Liu ₁ , Qianming Li ₁ , Xianzuo Zhang ₁ , Zheng Su ₁ , Xianli Hu ₁ , Wanbo Zhu ₂ , Ming Ye ₄ , Jiaxing Wang ₂ , Chen Zhu ₁

Affiliation

Bacterial biofilm-associated infections (BAIs) are the leading cause of prosthetic implant failure. The dense biofilm structure prevents antibiotic penetration, while the highly acidic and H₂O₂-rich biofilm microenvironment (BME) dampens the immunological response of antimicrobial macrophages. Conventional treatments that fail to consistently suppress escaping planktonic bacteria from biofilm result in refractory recolonization, allowing BAIs to persist. Herein, a BME-responsive copper-doped polyoxometalate clusters (Cu-POM) combination with mild photothermal therapy (PTT) and macrophage immune re-rousing for BAI eradication at all stages is proposed. The self-assembly of Cu-POM in BME converts endogenous H₂O₂ to toxic ·OH through chemodynamic therapy (CDT) and generates a mild PTT effect to induce bacterial metabolic exuberance, resulting in loosening the membrane structure of the bacteria, enhancing copper transporter activity and increasing intracellular Cu-POM flux. Metabolomics reveals that intracellular Cu-POM overload restricts the TCA cycle and peroxide accumulation, promoting bacterial cuproptosis-like death. CDT re-rousing macrophages scavenge planktonic bacteria escaping biofilm disintegration through enhanced chemotaxis and phagocytosis. Overall, BME-responsive Cu-POM promotes bacterial cuproptosis-like death via metabolic interference, while also re-rousing macrophage immune response for further planktonic bacteria elimination, resulting in all-stage BAI clearance and providing a new reference for future clinical application.

中文翻译：

生物膜微环境响应性自组装纳米反应器通过细菌铜中毒样死亡和巨噬细胞重新唤醒实现全阶段生物膜相关感染

细菌生物膜相关感染（BAIs）是假体植入失败的主要原因。致密的生物膜结构可防止抗生素渗透，而高酸性和富含H ₂ O ₂的生物膜微环境（BME）会抑制抗菌巨噬细胞的免疫反应。传统的治疗方法无法持续抑制从生物膜中逃逸的浮游细菌，导致难治性的再定殖，从而使 BAI 持续存在。在此，提出了一种 BME 响应性铜掺杂多金属氧酸盐簇 (Cu-POM) 与温和光热疗法 (PTT) 和巨噬细胞免疫重新唤醒相结合，用于在各个阶段根除 BAI。BME中Cu-POM的自组装通过化学动力学疗法（CDT）将内源性H ₂ O ₂转化为有毒的·OH，并产生温和的PTT效应，诱导细菌代谢旺盛，导致细菌膜结构松弛，增强铜转运蛋白活性和增加细胞内 Cu-POM 通量。代谢组学揭示细胞内 Cu-POM 过载限制 TCA 循环和过氧化物积累，促进细菌铜凋亡样死亡。CDT 重新唤醒巨噬细胞，通过增强趋化性和吞噬作用清除逃避生物膜崩解的浮游细菌。总体而言，BME响应性Cu-POM通过代谢干扰促进细菌铜凋亡样死亡，同时还重新唤醒巨噬细胞免疫反应以进一步消除浮游细菌，从而实现全阶段BAI清除，为未来的临床应用提供新的参考。

更新日期：2023-06-01

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南