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| 搭载达沙替尼的巨噬细胞膜囊泡用于缺血性脑卒中的治疗研究 | |
| 引用本文： | 张晓婷,张可,郭镜培,刘佳妮,周斌. 搭载达沙替尼的巨噬细胞膜囊泡用于缺血性脑卒中的治疗研究[J]. 中华介入放射学电子杂志, 2022, 10(2): 145-151. DOI: 10.3877/cma.j.issn.2095-5782.2022.02.005 |
| 作者姓名： | 张晓婷 张可 郭镜培 刘佳妮 周斌 |
| 作者单位： | 1. 519000 广东珠海，中山大学附属第五医院介入医学中心；519000 广东珠海，中山大学附属第五医院脑血管病中心2. 广东省生物医学影像 重点实验室；广东省分子影像技术工程研究中心 |
| 基金项目： | 国家自然科学基金(82102164); 广东省自然科学基金(2019A1515011223); 珠海市科技计划医疗卫生项目(ZH22036201210058PWC) |
| 摘 要： | 目的研究开发靶向缺血性大脑和跨血脑屏障的纳米载体，帮助达沙替尼（DAS）有效地输送到大脑，以减轻缺血性脑卒中（IS）后局部炎症反应和神经损伤。 方法提取巨噬细胞膜构建搭载DAS的纳米囊泡。经尾静脉给药IS小鼠后，通过各器官组织切片HE染色分析载药囊泡的生物安全性。采用荧光标记载药囊泡，利用活体成像和免疫荧光分析载药囊泡的大脑靶向性和生物分布。对不同治疗处理组做神经功能评分、死亡率统计和神经细胞计数，评估载药囊泡的神经保护作用。 结果载药囊泡在活体内具有良好的生物安全性，可快速高效靶向缺血侧脑组织内并被神经细胞摄取。对比单纯的DAS治疗，载药囊泡治疗可明显改善IS小鼠的神经功能，降低死亡率，减少神经细胞的凋亡。 结论研究证实搭载DAS的巨噬细胞膜纳米囊泡可安全高效靶向缺血侧大脑递药，有效发挥抗炎和神经保护作用，可为改善IS后药物治疗提供新思路。 |
| 关 键 词： | 缺血性脑卒中 达沙替尼 巨噬细胞膜 载药囊泡 靶向治疗 |
| 收稿时间： | 2022-04-07 |
Dasatinib-loaded macrophage membrane vesicles for the treatment of ischemic stroke |
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| Xiaoting Zhang,Ke Zhang,Jingpei Guo,Jiani Liu,Bin Zhou. Dasatinib-loaded macrophage membrane vesicles for the treatment of ischemic stroke[J]. Chinese Journal of Interventional Radiology (Electronic Edition), 2022, 10(2): 145-151. DOI: 10.3877/cma.j.issn.2095-5782.2022.02.005 | |
| Authors: | Xiaoting Zhang Ke Zhang Jingpei Guo Jiani Liu Bin Zhou |
| Abstract: | ObjectiveAims to develop nanocarrier targeting the ischemic brain and the blood-brain barrier help deliver dasatinib (DAS) effectively to the brain, so as to alleviate local inflammatory response and neuronal damage after ischemic stroke (IS). MethodsThe macrophages membranes were extracted to construct DAS-loaded nanovesicles. The biosafety of DAS-loaded vesicles in IS mice was analyzed by HE staining in tissue sections of each organ. The DAS-loaded vesicles were labeled with fluorescence. Then, the brain targeting characteristic and biological distribution of DAS-loaded vesicles were analyzed by in vivo imaging and immunofluorescence. Neurological function score, mortality statistics and neuron count were performed in different treatment groups to evaluate the neuroprotective effect of DAS-loaded vesicles. ResultsDAS-loaded vesicles had good biosafety in vivo. They could rapidly and efficiently target ischemic brain tissue and be taken up by neuron. Compared with DAS, DAS-loaded vesicles significantly improved the neurological function of IS mice, reduced the mortality rate and neuronal apoptosis. ConclusionsOur study confirmed that DAS-loaded macrophage membrane nanovesicles can safely and efficiently target the ischemic side of the brain, exert anti-inflammatory and neuroprotective effects. That provide new ideas for improving drug treatment after IS. |
| Keywords: | Ischemic stroke Dasatinib Macrophage membrane Drug-loaded nanovesicles Targeted therapy |
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