Surface-tethered ROS-responsive micelle backpacks for boosting mesenchymal stem cell vitality and modulating inflammation in ischemic stroke treatment

• Published in: Journal of controlled release 2023-10, Vol.362, p.210-224
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Cellular backpacks; Inflammation; Ischemic stroke; Luteolin; Mesenchymal stem cells
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2023.08.039

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. [Display omitted]