A "Nano-Courier" for Precise Delivery of Acetylcholine and Melatonin by C5a-Targeted Aptamers Effectively Attenuates Reperfusion Injury of Ischemic Stroke

作者全名："Xiao, Xinyu; Gao, Yu; Liu, Shanshan; Wang, Meijiao; Zhong, Min; Wang, Jianwei; Jiang, Ning; Peng, Qiling"

作者地址："[Xiao, Xinyu; Wang, Meijiao; Wang, Jianwei; Peng, Qiling] Chongqing Med Univ, Sch Basic Med Sci, Chongqing 400016, Peoples R China; [Gao, Yu; Jiang, Ning] Chongqing Med Univ, Affiliated Hosp 1, Mol Med Diagnost & Testing Ctr, Dept Pathol, Chongqing 400016, Peoples R China; [Liu, Shanshan] Chongqing Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Zhong, Min] Chongqing Med Univ, Dept Rehabil, Childrens Hosp, Chongqing 400016, Peoples R China"

通信作者："Wang, JW; Peng, QL (通讯作者)，Chongqing Med Univ, Sch Basic Med Sci, Chongqing 400016, Peoples R China.; Jiang, N (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Mol Med Diagnost & Testing Ctr, Dept Pathol, Chongqing 400016, Peoples R China."

来源：ADVANCED FUNCTIONAL MATERIALS

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000950408500001

JCR分区：Q1

影响因子：18.5

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：biocompatible nanospheres; inflammatory responses; ischemic strokes; oxidative stress; reperfusion injury

摘要："Overactive inflammatory response and excessive oxidative stress are the main pathophysiological culprits for cerebral ischemia/reperfusion injury (IRI) that arouse neuronal damage . The neurotransmitter acetylcholine (ACh) exerts anti-inflammatory roles by stimulating alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) on microglia to activate the cholinergic anti-inflammatory pathway. Simultaneously, as a circadian rhythm-dependent hormone , melatonin (MT) possesses promising neuroprotective effects that eliminate reactive oxygen species (ROS) in the ischemic region. Relying on these, a biocompatible fluorescein isothiocyanate (FITC)-labeled SiO2@PAA-MT/ACh nanospheres are constructed to effectively alleviate oxidative stress and polarize microglial phenotype to suppress inflammatory response in cerebral IRI. Despite of biosafety and curative effects of ACh and MT, the poor aggregation in ischemic penumbra hinders their neuroprotection. To address that, complement component 5a (C5a) is used as a molecular target for delivery of ACh and MT. C5a conspicuously exists at local inflammatory sites of cerebral IRI, recruits immune cells, and mediates further release of inflammatory cytokines. Upon binding of anti-C5a (aC5a) aptamers onto FITC-labeled SiO2@PAA-MT/ACh nanospheres, they can effectively target the ischemic penumbra and promote neurological recovery. Taken together, the current study suggests that the FITC-labeled SiO2@PAA-MT/ACh-aC5a nanospheres after intravenous (i.v.) administration can act as an effective targeted nanotherapy to salvage neurons in cerebral IRI."

基金机构："National Natural Science Foundation of China [81972023]; Natural Science Foundation of Chongqing City [CSTC2020jcyj-msxmX0144, CSTC2021jcyj-msxm0172, CSTB2022NSCQ-MSX0054]; Science and Technology Research Program of Chongqing Education Commission of China [KJQN201900425, KJQN202000401]; Creative Research Group of CQ University [CXQT21017]; Province Natural Science Foundation of Jiangxi Province [20202BABL216040]; Program for Youth Innovation in Future Medicine from Chongqing Medical University"

基金资助正文："X.X., Y.G., and S.L. contributed equally to this work. This work was supported by the National Natural Science Foundation of China (grant no. 81972023), the Natural Science Foundation of Chongqing City (grant no. CSTC2020jcyj-msxmX0144, CSTC2021jcyj-msxm0172, and CSTB2022NSCQ-MSX0054), the Science and Technology Research Program of Chongqing Education Commission of China (grant no. KJQN201900425 and KJQN202000401), the Creative Research Group of CQ University (grant no. CXQT21017), the Province Natural Science Foundation of Jiangxi Province (grant no. 20202BABL216040), and the Program for Youth Innovation in Future Medicine from Chongqing Medical University. The authors acknowledge with thanks the ethics committee of the First Affiliated Hospital of Chongqing Medical University for the ethical approval of this study."