PSL公司
白细胞介素10
脑出血
小胶质细胞
医学
神经炎症
脂质体
药理学
免疫学
细胞因子
癌症研究
内科学
材料科学
炎症
纳米技术
数学
几何学
蛛网膜下腔出血
作者
Ranran Han,Xi Lan,Zheng Han,Honglei Ren,Safiya Aafreen,Wenshen Wang,Zhipeng Hou,Tianyue Zhu,Andrew Qian,Xiaoning Han,Raymond C. Koehler,Guanshu Liu
出处
期刊:Biomaterials
[Elsevier]
日期:2023-08-15
卷期号:301: 122277-122277
被引量:21
标识
DOI:10.1016/j.biomaterials.2023.122277
摘要
Intracerebral hemorrhage (ICH) remains the most lethal type of stroke, and effective clinical therapies that can speed up hematoma resolution after ICH are still lacking. While the beneficial effects of IL-10 on ICH recovery have been demonstrated, the clinical translation of IL-10 requires effective delivery methods by which sufficient IL-10 can be delivered to ICH-affected regions in the brain. Here we report the use of a phosphatidylserine (PS) liposome (PSL)-based nanoparticle system for microglia/macrophage-targeted delivery of IL-10 in ICH. We first prepared IL-10-conjugated PSL (PSL-IL10) and characterized their immunomodulating effects in vitro. Then we evaluated the therapeutic effects, including hematoma absorption, short-term outcomes, and neuroinflammation, of intranasally administered PSL-IL10 (3 μg IL-10 per mouse, 2 h post-ICH) in a collagenase-induced ICH mouse model. We also isolated microglia/macrophages from the mouse brains with ICH to analyze their morphology, phagocytosis ability, and polarization. Our study reveals that, 1) PSL-IL10 treatment resulted in significantly improved outcomes and accelerated hematoma resolution in the acute phase of ICH; 2) PSL-IL10 inhibited glial activation and down-regulated pro-inflammatory cytokine production; 3) PSL-IL10 induced Iba1+ cells with a stronger phagocytosis ability; 4) PSL-IL10 activated STAT3 and upregulated CD36 expression in microglia/macrophage. These findings collectively show that PSL-IL10 is a promising nanotherapeutic for effectively ameliorating ICH.
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