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

Yang You; Yipu Liu; Chuchu Ma; Jianpei Xu; Laozhi Xie; Shiqiang Tong; Yinzhe Sun; Fenfen Ma; Yukun Huang; Junbin Liu; Wenze Xiao; Chengxiang Dai; Suke Li; Jigang Lei; Qiyong Mei; Xiaoling Gao; Jun Chen

doi:10.1016/j.jconrel.2023.08.039

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

J Control Release. 2023 Oct:362:210-224. doi: 10.1016/j.jconrel.2023.08.039. Epub 2023 Aug 31.

Authors

Yang You¹, Yipu Liu¹, Chuchu Ma¹, Jianpei Xu¹, Laozhi Xie¹, Shiqiang Tong¹, Yinzhe Sun¹, Fenfen Ma¹, Yukun Huang², Junbin Liu³, Wenze Xiao⁴, Chengxiang Dai⁵, Suke Li⁶, Jigang Lei⁶, Qiyong Mei⁷, Xiaoling Gao⁸, Jun Chen⁹

Affiliations

¹ 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.
² 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.
³ Department of Neurosurgery, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai 200003, China.
⁴ Department of Rheumatology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Shanghai 201399, China.
⁵ Daxing Research Institute, University of Science and Technology Beijing, 41 Yongda Road, Biomedical Industry Base, Zhongguancun Science and Technology Park, Daxing District, Beijing 102600, China; Cellular Biomedicine Group, Inc., 85 Faladi Road, Building 3, Zhangjiang, Pudong New Area, Shanghai 201210, China.
⁶ Cellular Biomedicine Group, Inc., 85 Faladi Road, Building 3, Zhangjiang, Pudong New Area, Shanghai 201210, China.
⁷ Department of Neurosurgery, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai 200003, China. Electronic address: meiqiyong@smmu.edu.cn.
⁸ 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. Electronic address: shellygao1@sjtu.edu.cn.
⁹ 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. Electronic address: chenjun@fudan.edu.cn.

PMID: 37619863
DOI: 10.1016/j.jconrel.2023.08.039

Abstract

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.

Keywords: Cellular backpacks; Inflammation; Ischemic stroke; Luteolin; Mesenchymal stem cells.