文献类型：期刊文献

英文题名：Controlled delivery of a neurotransmitter-agonist conjugate for functional recovery after severe spinal cord injury

作者：Zuo, Yanming[1,2,3,4];Ye, Jingjia[1,2,3,4];Cai, Wanxiong[3,4];Guo, Binjie[3,4];Chen, Xiangfeng[3,4];Lin, Lingmin[3,4];Jin, Shuang[3,4];Zheng, Hanyu[3,4];Fang, Ao[3,4];Qian, Xingran[3,4];Abdelrahman, Zeinab[1,2,3,4];Wang, Zhiping[3,4];Zhang, Zhipeng[5];Chen, Zuobin[1,2];Yu, Bin[6,7];Gu, Xiaosong[6,7];Wang, Xuhua[1,2,3,4,8]

机构：[1]Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Neurobiol, Hangzhou, Peoples R China;[2]Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept Rehabil Med, Hangzhou, Peoples R China;[3]Zhejiang Univ, MOE Frontier Sci Ctr Brain Sci & Brain Machine Int, Liangzhu Lab, State Key Lab Brain Machine Intelligence, Hangzhou, Peoples R China;[4]Zhejiang Univ, NHC & CAMS Key Lab Med Neurobiol, Hangzhou, Peoples R China;[5]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Sch Chem & Mol Engn, Shanghai, Peoples R China;[6]Nantong Univ, Key Lab Neuroregenerat Jiangsu, Nantong, Peoples R China;[7]Nantong Univ, Minist Educ, Nantong, Peoples R China;[8]Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong, Peoples R China

年份：2023

卷号：18

期号：10

起止页码：1230

外文期刊名：NATURE NANOTECHNOLOGY

收录：;EI(收录号：20232414252597);WOS:【SCI-EXPANDED(收录号:WOS:001004926500001)】；

基金：We acknowledge the excellent technical staff at the Imaging Facility, Core Facility of Zhejiang University School of Medicine and Center of Cryo-Electron Microscopy of Zhejiang University for their assistance with confocal laser scanning microscopy and TEM. This study was supported by the Scientific and Technological Innovation 2030 Program of China, major projects (2021ZD0200408 to X.W.); the National Natural Science Foundation of China (81971866 to X.W.); the Science Fund for Distinguished Young Scholars of Zhejiang Province (LR20H090002 to X.W.); the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang (2019R01007 to X.W.); the Fundamental Research Funds for the Central Universities (K20210195 to X.W.); and the National Major Project of Research and Development (2017YFA0104701 to B.Y.).

语种：英文

外文关键词：Neurophysiology - Patient rehabilitation - Recovery

摘要：Here the authors report the delivery of neurotransmitter-conjugated KCC2 agonist using a reactive oxygen species-responsive polymer nanoparticle that can cross the damaged blood-spinal cord barrier and significantly increase recovery after spinal cord injury in vivo. Despite considerable unmet medical needs, effective pharmacological treatments that promote functional recovery after spinal cord injury remain limited. Although multiple pathological events are implicated in spinal cord injuries, the development of a microinvasive pharmacological approach that simultaneously targets the different mechanisms involved in spinal cord injury remains a formidable challenge. Here we report the development of a microinvasive nanodrug delivery system that consists of amphiphilic copolymers responsive to reactive oxygen species and an encapsulated neurotransmitter-conjugated KCC2 agonist. Upon intravenous administration, the nanodrugs enter the injured spinal cord due to a disruption in the blood-spinal cord barrier and disassembly due to damage-triggered reactive oxygen species. The nanodrugs exhibit dual functions in the injured spinal cord: scavenging accumulated reactive oxygen species in the lesion, thereby protecting spared tissues, and facilitating the integration of spared circuits into the host spinal cord through targeted modulation of inhibitory neurons. This microinvasive treatment leads to notable functional recovery in rats with contusive spinal cord injury.