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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1543870
This article is part of the Research Topic New Approaches To Overcome the Blood-Brain Barrier for the Treatment of CNS Disorders View all 3 articles
A ROS-Responsive, Aptamer-Targeted Graphene Oxide Nanocomposite for Site-Specific Glutathione Release in Cerebral Ischemia-Reperfusion Injury
Provisionally accepted
Jingxin Mo 1*
Meiying Li 1,2 Lili Wei 3 Wenxu Liu 2 Jiawen Wang 1 Qiujie Lu 4 Xianjue Chen 5 Lee Yong Lim 6- 1 Lab of Neurology, Affiliated Hospital of Guilin Medical University, Guilin, China
- 2 School of Pharmacy, Guilin Medical University, Guilin, Guangxi Zhuang Region, China
- 3 Pharmaceutical Clinical Trial Laboratory, Affiliated Hospital of Guilin Medical University, Guilin, China
- 4 School of Clinical Medicine, Guilin Medical University, Guilin, Guangxi Zhuang Region, China
- 5 The University of Newcastle, Callaghan, New South Wales, Australia
- 6 University of Western Australia, Perth, Western Australia, Australia
Cerebral ischemia-reperfusion (I/R) injury is a major contributor to mortality and longterm disability worldwide, primarily due to excessive reactive oxygen species (ROS) generation after blood flow is restored. Although current treatments focus on reestablishing perfusion, they offer limited protection against the secondary ROSmediated injury. Here, we report a multifunctional nanocomposite-graphene oxide loaded with glutathione (GSH) and functionalized with a fibrinogen-targeting aptamer (GO@GSH-FA)-capable of selectively releasing antioxidant cargo within the ischemic brain microenvironment. Characterization revealed a drug-loading capacity of 17.59 ± 3.74% and an entrapment efficiency of 78.78 ± 4.55%, highlighting the robust loading of GSH. The ROS-sensitive borate ester linker ensures that GSH is preferentially liberated in oxidative stress regions, while the fibrinogen aptamer actively targets fibrin-rich thrombotic sites. In vitro, GO@GSH-FA significantly restored viability in oxygen-glucose-deprived SH-SY5Y cells (from 31% up to near control levels), reduced inflammatory cytokines, and lowered intracellular ROS. In a Endothelin-1 (ET-1) induced cortical ischemia model, GO@GSH-FA led to a marked decrease in neurological deficit scores (from 7.20 ± 1.16 to 4.20 ± 0.98) and enhanced neuronal survival relative to untreated animals. Collectively, these findings underscore the promise of GO@GSH-FA as a targeted, ROS-responsive platform for mitigating cerebral I/R injury.
Keywords: Glutathione, Cerebral ischemia-reperfusion injury, graphene oxide, Oxidative Stress, Fibrinogen Aptamer
Received: 12 Dec 2024; Accepted: 25 Mar 2025.
Copyright: © 2025 Mo, Li, Wei, Liu, Wang, Lu, Chen and Lim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jingxin Mo, Lab of Neurology, Affiliated Hospital of Guilin Medical University, Guilin, China
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