Decoy Nanozymes Enable Multitarget Blockade of Proinflammatory Cascades for the Treatment of Multi-Drug-Resistant Bacterial Sepsis
Xuancheng Du,
Mingzhen Zhang,
Huiting Zhou,
Weijie Wang,
Chengmei Zhang,
Lei Zhang,
Yuanyuan Qu,
Weifeng Li,
Xiangdong Liu,
Mingwen Zhao,
Kangsheng Tu,
Yong-Qiang Li
Affiliations
Xuancheng Du
Institute of Advanced Interdisciplinary Science, School of Physics, Shandong University, Jinan 250100, China
Mingzhen Zhang
School of Basic Medical Sciences, Xi’an Key Laboratory of Immune Related Diseases, Xi’an Jiaotong University, Xi’an 710061, China
Huiting Zhou
Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou 215025, China
Weijie Wang
Institute of Advanced Interdisciplinary Science, School of Physics, Shandong University, Jinan 250100, China
Chengmei Zhang
Laboratory Animal Center of Shandong University, Jinan 250012, China
Lei Zhang
Department of Critical Care Medicine, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
Yuanyuan Qu
Institute of Advanced Interdisciplinary Science, School of Physics, Shandong University, Jinan 250100, China
Weifeng Li
Institute of Advanced Interdisciplinary Science, School of Physics, Shandong University, Jinan 250100, China
Xiangdong Liu
Institute of Advanced Interdisciplinary Science, School of Physics, Shandong University, Jinan 250100, China
Mingwen Zhao
Institute of Advanced Interdisciplinary Science, School of Physics, Shandong University, Jinan 250100, China
Kangsheng Tu
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
Yong-Qiang Li
Institute of Advanced Interdisciplinary Science, School of Physics, Shandong University, Jinan 250100, China; Suzhou Research Institute, Shandong University, Suzhou 215123, China; College of Chemistry, Chemical Engineering and Materials Science, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan 250014, China
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@MΦ) consist mesoporous silica nanoparticle cores loaded with CeO2 nanocatalyst and Ce6 photosensitizer and biomimetic shells of macrophage membrane. By acting as macrophage decoys, MCeC@MΦ allow targeted photodynamic eradication of MDR bacteria and realize simultaneous endotoxin/proinflammatory cytokine neutralization. Meanwhile, MCeC@MΦ 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@MΦ 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@MΦ considerably attenuate systemic hyperinflammation and rapidly rescue organ damage within 1 day to confer higher survival rates (>75%) to mice with progressive MDR Escherichia coli bacteremia. The proposed decoy nanozyme-enabled multitarget collaborative intervention strategy offers a powerful modality for bacterial sepsis management and opens up possibilities for the treatment of cytokine storm in the COVID-19 pandemic and immune-mediated inflammation diseases.
