J Nanobiotechnology. 2025 Aug 21;23(1):579. doi: 10.1186/s12951-025-03639-w.
ABSTRACT
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.
PMID:40841659 | DOI:10.1186/s12951-025-03639-w
