Decoy Nanozymes Enable Multitarget Blockade of Proinflammatory Cascades for the Treatment of Multi-Drug-Resistant Bacterial Sepsis

作者：Xuancheng Du, Mingzhen Zhang, Huiting Zhou, Weijie Wang, Chengmei Zhang, Lei Zhang, Yuanyuan Qu, Weifeng Li, Xiangdong Liu, Mingwen Zhao, Kangsheng Tu, Yongqiang Li · 发表于：Research · 年份：2022 · DOI：10.34133/2022/9767643 · 被引用次数：59 · 研究领域：Advanced Nanomaterials in Catalysis、Nanoplatforms for cancer theranostics、Neuroinflammation and Neurodegeneration Mechanisms

Sepsis is a life-threatening organ dysfunction characterized by severe systemic inflammatory response to infection. Effective treatment of bacterial sepsis remains a paramount clinical challenge, due to its astonishingly rapid progression and the prevalence of bacterial drug resistance. Here, we present a decoy nanozyme-enabled intervention strategy for multitarget blockade of proinflammatory cascades to treat multi-drug-resistant (MDR) bacterial sepsis. The decoy nanozymes (named MCeC@M Φ ) consist mesoporous silica nanoparticle cores loaded with CeO 2 nanocatalyst and Ce6 photosensitizer and biomimetic shells of macrophage membrane. By acting as macrophage decoys, MCeC@M Φ allow targeted photodynamic eradication of MDR bacteria and realize simultaneous endotoxin/proinflammatory cytokine neutralization. Meanwhile, MCeC@M Φ possess intriguing superoxide dismutase and catalase-like activities as well as hydroxyl radical antioxidant capacity and enable catalytic scavenging of multiple reactive oxygen species (ROS). These unique capabilities make MCeC@M Φ to collaboratively address the issues of bacterial infection, endotoxin/proinflammatory cytokine secretion, and ROS burst, fully cutting off the path of proinflammatory cascades to reverse the progression of bacterial sepsis. In vivo experiments demonstrate that MCeC@M Φ considerably attenuate systemic hyperinflammation and rapidly rescue organ damage within 1 day to confer higher survival rates (>75%) to mice with progressi...