CeO2@mSiO2 core-shell nanozymes with pH-responsive resveratrol release for oxidative stress and inflammation regulation in spinal cord injury

Secondary injury after spinal cord injury (SCI) is characterized by persistent oxidative stress and neuroinflammation, which create a hostile microenvironment that limits neuronal regeneration. Herein, an interfacially engineered core-shell nanozyme system (CeO 2 @mSiO 2 -RES) was developed for integrated regulation of the oxidative-inflammatory microenvironment. The CeO 2 core exhibited mixed Ce 3+ /Ce 4+ states and CAT- and SOD-like activities, while the mesoporous SiO 2 shell enabled efficient RES loading and pH-dependent release. In vitro, CeO 2 @mSiO 2 -RES reduced intracellular ROS accumulation and restored CAT, SOD, and GSH antioxidant defenses. It also decreased iNOS expression while increasing Arg-1 expression in LPS-stimulated macrophages. Furthermore, CeO 2 @mSiO 2 -RES enhanced NGF-induced neurite outgrowth and MAP2 expression under inflammatory stress. Collectively, these findings suggest that CeO 2 @mSiO 2 -RES can regulate the oxidative-inflammatory microenvironment and provide a potential nanomaterial-based strategy for neuronal repair after SCI. Download: Download high-res image (383KB) Download: Download full-size image