医学
体内
药理学
神经保护
冲程(发动机)
缺血
炎症
血脑屏障
缺血性中风
麻醉
内科学
免疫学
中枢神经系统
生物
机械工程
生物技术
工程类
作者
Weili Jin,Ye Wu,Ning Chen,Qixue Wang,Yunfei Wang,Yansheng Li,Sidi Li,Xing Han,Eryan Yang,Fei Tong,Jialing Wu,Xubo Yuan,Chunsheng Kang
出处
期刊:Theranostics
[Ivyspring International Publisher]
日期:2021-01-01
卷期号:11 (17): 8197-8217
被引量:13
摘要
Ischemic stroke is an acute and severe neurological disease, which leads to disability and death.Immunomodulatory therapies exert multiple remarkable protective effects during ischemic stroke.However, patients suffering from ischemic stroke do not benefit from immunomodulatory therapies due to the presence of the blood-brain barrier (BBB) and their off-target effects.Methods: We presented a delivery strategy to optimize immunomodulatory therapies by facilitating BBB penetration and selectively delivering intravenous immunoglobulin (IVIg) to ischemic regions using 2-methacryloyloxyethyl phosphorylcholine (MPC)-nanocapsules, MPC-n(IVIg), synthesized using MPC monomers and ethylene glycol dimethyl acrylate (EGDMA) crosslinker via in situ polymerization.In vitro and in vivo experiments verify the effect and safety of MPC-n(IVIg).Results: MPC-n(IVIg) efficiently crosses the BBB and IVIg selectively accumulates in ischemic areas in a high-affinity choline transporter 1 (ChT1)-overexpression dependent manner via endothelial cells in ischemic areas.Moreover, earlier administration of MPC-n(IVIg) more efficiently deliver IVIg to ischemic areas.Furthermore, the early administration of low-dosage MPC-n(IVIg) decreases neurological deficits and mortality by suppressing stroke-induced inflammation in the middle cerebral artery occlusion model. Conclusion:Our findings indicate a promising strategy to efficiently deliver the therapeutics to the ischemic target brain tissue and lower the effective dose of therapeutic drugs for treating ischemic strokes.
科研通智能强力驱动
Strongly Powered by AbleSci AI