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Nasal-to-Brain ROS-Responsive Diselenide-Bridged Graphene Nanogel for Targeted Ischemic Stroke Therapy via Microglial
Jiawen Wang1, Qiujie Lu2, Qinghua Li3,4,5
1Laboratory of Neuroscience, The First Affiliated Hospital of Guilin Medical University, Lequn Road, Xiufeng District, Guilin 541001, China.
ACS Omega
|July 24, 2026
Summary
A novel nanogel delivers Dauricine to the brain, reducing oxidative stress and neuroinflammation after ischemic stroke. This treatment improved neurological function and brain protection in a mouse model.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Neuroscience
Background:
- Ischemic stroke causes neuronal death, blood-brain barrier (BBB) disruption, and neurological deficits due to secondary oxidative stress and neuroinflammation.
- Effective therapeutic strategies require addressing these intertwined injury cascades for enhanced neuroprotection.
Purpose of the Study:
- To develop and evaluate a novel diselenide-bridged hyaluronic acid/graphene oxide quantum dot nanogel (DRC@GOQD-HA-Se) for intranasal delivery of Dauricine.
- To investigate the nanogel's antioxidant, ROS-scavenging, and immunomodulatory properties for treating ischemic stroke.
Main Methods:
- Developed DRC@GOQD-HA-Se nanogel for intranasal delivery of Dauricine, utilizing diselenide cross-links for ROS-triggered release and a hyaluronic acid shell for targeting and BBB bypass.
- Assessed ROS scavenging capacity, in vitro effects on microglial polarization and neuronal apoptosis under oxygen-glucose deprivation/reoxygenation (OGD/R) insult.
- Evaluated therapeutic efficacy in a photothrombotic ischemia (PTI) mouse model, measuring infarct size, neurological deficits, learning ability, and locomotor activity. Analyzed underlying molecular mechanisms and performed biodistribution and toxicity studies.
Main Results:
- DRC@GOQD-HA-Se demonstrated potent ROS scavenging (eliminating •OH, O2•−, and degrading H2O2) and successfully delivered Dauricine via intranasal administration.
- In the PTI mouse model, treatment significantly reduced infarct size, improved neurological deficit scores (~40%), learning (halved escape latency), and locomotor activity (~61%).
- In vitro studies showed inhibition of M1 microglial polarization, reduced neuronal apoptosis, and preserved mitochondrial function. Mechanistic studies revealed modulation of STAT3/iNOS and TLR4/MyD88/NF-κB signaling pathways. Biodistribution confirmed enhanced brain accumulation (>5-fold) with no systemic toxicity.
Conclusions:
- The developed DRC@GOQD-HA-Se nanoplatform effectively scavenges ROS, modulates neuroinflammation, and facilitates targeted nose-to-brain delivery of Dauricine.
- This multifunctional nanogel represents a promising, clinically translatable strategy for neuroprotection and functional recovery after ischemic stroke.
- The study highlights the potential of integrated nanomedicine approaches for complex neurological disorders.
