Oxygen-Vacancy-Rich Monolayer BiO_2- _X Nanosheets for Bacterial Sepsis Management via Dual Physically Antibacterial and Chemically Anti-inflammatory Functions.

Abstract

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Effective treatment of bacterial sepsis remains challenging due to the rapid progression of infection and the systemic inflammatory response. In this study, monolayer BiO_2- _X nanosheets (BiO_2- _X NSs) with oxygen-rich vacancies through sonication-assisted liquid-phase exfoliation are successfully synthesized. Herein, the BiO_2- _X NSs exhibit a novel nanozyme-enabled intervention strategy for the management of bacterial sepsis, based on its pH dependent dual antibacterial and anti-inflammatory functions. BiO_2- _X NSs exhibit effective antibacterial by utilizing oxidase (OXD)-like activity. Additionally, BiO_2- _X NSs can scavenge multiple reactive oxygen species (ROS) and mitigate systemic hyperinflammation by mimicking superoxide dismutase (SOD) and catalase (CAT). These dual capabilities of BiO_2- _X NSs allow them to address bacterial infection, proinflammatory cytokines secretion and ROS burst collaboratively, effectively reversing the progression of bacterial sepsis. In vivo experiments have demonstrated that BiO_2- _X NSs significantly reduce bacterial burden, attenuate systemic hyperinflammation, and rapidly rescued organ damage. Importantly, no obvious adverse effects are observed at the administered dose of BiO_2- _X NSs. This study presents a novel defect engineering strategy for the rational design of high-performance nanozymes and development of new nanomedicines for managing bacterial sepsis.