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

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

  • J Nanobiotechnology. 2025 Aug 21;23(1):579. doi: 10.1186/s12951-025-03639-w.
Yi Chang # 1,  Xue Zhang # 2,  Shuo Zhang 3,  Ge Qu 4
Affiliations

Affiliations

  • 1 Department of Anesthesiology, the First Hospital of China Medical University, Nanjingbei Street 155#, Shenyang, 110001, Liaoning Province, China.
  • 2 Department of Gynecology, the First Hospital of China Medical University, Nanjingbei Street 155#, Shenyang, 110001, Liaoning Province, China.
  • 3 Department of Anesthesiology, the First Hospital of China Medical University, Nanjingbei Street 155#, Shenyang, 110001, Liaoning Province, China. zhangshuo1005@sina.com.
  • 4 Department of Anesthesiology, the First Hospital of China Medical University, Nanjingbei Street 155#, Shenyang, 110001, Liaoning Province, China. 546653916@qq.com.
  • # Contributed equally.
PMID: 40841659 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.

Keywords

Angiopep-2/SIRT1 nanoparticles; Developmental neurotoxicity; Multi-omics; Necroptosis; Sevoflurane.

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