Multimodal hybrid nanozymes with antioxidant catalytic and antibiotic-free antibacterial activities for enhanced multi-target sepsis therapy

作者：Kai Zhu, Bowen Zhang, Yanhua Li, Yingwei Pan, Shikun Zhang, Haowen Tang, Zhanyu Yang, Xuan Tang, Xiaoyong Zhang, Wanyi Chen, Quan Wang, Shujie Ma, Lian Zhao, Yongming Yao, Hong Zhou, Gan Chen · 发表于：Cell Reports Medicine · 年份：2026 · DOI：10.1016/j.xcrm.2025.102541 · 被引用次数：4 · 研究领域：Advanced Nanomaterials in Catalysis、Nanoplatforms for cancer theranostics、Ferroptosis and cancer prognosis

Sepsis, characterized by its complex pathophysiology, presents significant challenges for clinical treatment. An integrative approach combining highly effective antibacterial measures, immunomodulation, and organ protection is urgently needed to enhance the therapeutic efficacy. Here, we construct hybrid cerium-baicalein nanozymes (Ce-BE NZs), which exhibit broad-spectrum non-antibiotic antibacterial and redox enzyme-mimicking activities, effectively scavenging reactive oxygen species and reducing inflammatory mediators in lipopolysaccharide-stimulated macrophages. Ce-BE NZs also correct immune dysregulation, reduce liver injury, and extend survival in both cecal ligation and puncture and "two-hit" sepsis models. Mechanistically, Ce-BE NZs inhibit ferroptosis and mitigate mitochondrial dysfunction by promoting ferritin heavy chain-1 expression, thereby enhancing multi-target sepsis therapy. Additionally, they mitigate ferroptosis and cell damage in a macrophage-incorporating human liver-derived organoid model. Overall, Ce-BE NZs represent a promising multi-target therapy for sepsis and may pave the way for an antibiotic-free and transnational approach to treating other infectious diseases.