You Yang, Liu Yipu, Ma Chuchu, Xu Jianpei, Xie Laozhi, Tong Shiqiang, Sun Yinzhe, Ma Fenfen, Huang Yukun, Liu Junbin, Xiao Wenze, Dai Chengxiang, Li Suke, Lei Jigang, Mei Qiyong, Gao Xiaoling, Chen Jun
Shanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai 201203, China; Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai 201203, China.
Department of Pharmacology and Chemical Biology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Universities Collaborative Innovation Center for Translational Medicine, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
J Control Release. 2023 Oct;362:210-224. doi: 10.1016/j.jconrel.2023.08.039. Epub 2023 Aug 31.
Mesenchymal stem cells (MSCs) exhibited remarkable therapeutic potential in ischemic stroke due to their exceptional immunomodulatory ability and paracrine effect; they have also been regarded as excellent neuroprotectant delivery vehicles with inflammatory tropism. However, the presence of high levels of reactive oxygen species (ROS) and an oxidative stress environment at the lesion site inhibits cell survival and further therapeutic effects. Using bioorthogonal click chemistry, ROS-responsive luteolin-loaded micelles were tethered to the surface of MSCs. As MSCs migrated to the ischemic brain, the micelles would achieve ROS-responsive release of luteolin to protect MSCs from excessive oxidative damage while inhibiting neuroinflammation and scavenging ROS to ameliorate ischemic stroke. This study provided an effective and prospective therapeutic strategy for ischemic stroke and a framework for a stem cell-based therapeutic system to treat inflammatory cerebral diseases.
间充质干细胞（MSCs）因其卓越的免疫调节能力和旁分泌作用，在缺血性中风中展现出显著的治疗潜力；它们也被视为具有炎症趋向性的优良神经保护剂递送载体。然而，病变部位高水平活性氧（ROS）的存在和氧化应激环境会抑制细胞存活及进一步的治疗效果。利用生物正交点击化学，将负载ROS响应性木犀草素的胶束连接到MSCs表面。随着MSCs迁移至缺血性脑，胶束会实现木犀草素的ROS响应性释放，以保护MSCs免受过度氧化损伤，同时抑制神经炎症并清除ROS，从而改善缺血性中风。本研究为缺血性中风提供了一种有效且具有前景的治疗策略，以及一个基于干细胞的治疗系统来治疗炎症性脑部疾病的框架。
