Blood-brain barrier-penetrating Angiopep-2/Sirtuin 1 nanoparticles rescue sevoflurane neurotoxicity through multi-omics identified necroptosis pathways

作者：Yi Chang, Xue Zhang, Shuo Zhang, Ge Qu · 发表于：Journal of Nanobiotechnology · 年份：2025 · DOI：10.1186/s12951-025-03639-w · 被引用次数：4 · 研究领域：Anesthesia and Neurotoxicity Research、Neuroscience and Neuropharmacology Research、Cardiac Ischemia and Reperfusion

Developmental neurotoxicity (DNT) induced by sevoflurane exposure poses significant risks to pediatric anesthesia, yet effective protective strategies remain limited. Here, we developed self-assembling Angiopep-2/SIRT1 nanoparticles (Ang/SIRT1-NPs) with favorable biocompatibility and brain-targeting properties. Through in vitro and in vivo studies, we demonstrate that Ang/SIRT1-NPs effectively alleviate sevoflurane-induced neuronal apoptosis, neuroinflammation, and dendritic spine loss. Multi-omics analyses identified SIRT1-mediated suppression of necroptosis and oxidative stress pathways as key mechanisms underlying neuroprotection. Behavioral assays further confirmed improved cognitive and motor function in nanoparticle-treated mice. Our findings highlight the potential of Ang/SIRT1-NPs as a promising neuroprotective strategy for preventing anesthesia-related DNT and support their translational application in pediatric neuroprotection.