Synergistic microglial modulation by laminarin-based platinum nanozymes for potential intracerebral hemorrhage therapy

Abstract

Abnormal microglial activation increases inflammation, causing significant brain damage after intracerebral hemorrhage (ICH). To aid recovery, treatments should regulate oxidative stress and inhibit the M1-like phenotype (pro-inflammation) of microglia. Recently, antioxidant nanozymes have emerged as tools for modulating microglial states, but detailed studies on their role in ICH treatment are limited. To address this, we developed an ultra-small (3–4 nm) laminarin-modified platinum nanozyme (Pt@LA) for the synergistic regulation of microglial polarization, offering a novel therapeutic strategy for ICH. Pt@LA effectively scavenges reactive oxygen species (ROS) through superoxide dismutase (SOD) and catalase (CAT)-like activities. Laminarin may inhibit the Dectin-1 receptor on microglia and its inflammatory pathway, Syk/NF-κB, reducing neuroinflammation. In vitro, Pt@LA decreased pro-inflammatory microglia and cytokine expression by inhibiting the Dectin-1/Syk/NF-κB and ROS-mediated NF-κB pathways. Furthermore, Pt@LA protected neurons, inhibited glial scar formation, and improved neurological function in ICH rats. Overall, this study presents Pt nanozymes based on naturally extracted laminarin and explores their application in alleviating oxidative stress and neuroinflammation after ICH, bridging nanozyme research and neuroscience.