NIR Driven Pd/Cerium Oxide Nano-Heterojunction for Enhanced Salvaging Sepsis Induced Acute Liver Injury via Reprogramming Redox Homeostasis in Synergy with Inducing Autophagy

Adv Sci (Weinh). 2025 Jun 29:e17252. doi: 10.1002/advs.202417252. Online ahead of print.

Abstract

Sepsis induced acute liver injury (SALI), is a type of acute and severe disease that is generally characterized by producing significant amounts of reactive oxygen species (ROS) in liver tissue, and in response to excessive ROS, producing huge amounts of inflammatory factors by hepatocytes. Considering the crucial role of ROS in SALI, a Pd doped CeO2 (CP) nano-heterojunction with enhanced ROS scavenging capacity is developed to act as a catalytic nanomedicine for the treatment of SALI. Combining with near infrared (NIR) irradiation, it exhibits excellent scavenging capacity of ROS including hydroxyl radical (•OH), superoxide anion (•O2 -), as well as singlet oxygen (1O2) for CP. Significantly, it also demonstrates the excellent antioxidant and anti-inflammatory activities for lipopolysaccharides (LPS) stimulated macrophages (RAW264.7), and cecum ligation and puncture (CLP) treated C57BL/6J mice via reducing intracellular ROS levels, decreasing inflammatory factors expression levels, as well as activating Keap1/Nrf-2/HO-1 pathway to reprogram redox homeostasis, induce cellular autophagy, reduce systemic inflammation and promote liver tissue repair, finally achieving the alleviation of SALI. It provides a promising therapeutic strategy of CP+NIR with high efficacy and biosafety for the management of SALI.

Keywords: ROS scavenging; autophagy induction; keap1/Nrf‐2/HO‐1 pathway activation; redox homeostasis reprogramming; sepsis induced acute liver injury.