Preferential Targeting Cerebral Ischemic Lesions with Cancer Cell-Inspired Nanovehicle for Ischemic Stroke Treatment
Preferential Targeting Cerebral Ischemic Lesions with Cancer Cell-Inspired Nanovehicle for Ischemic Stroke Treatment
复制标题
利用癌细胞启发的纳米载体优先靶向脑缺血性病变治疗缺血性中风
DOI：
10.1021/acs.nanolett.1c00231
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发表时间：
2021-03-23
期刊：
影响因子：
10.8
通讯作者：
Sha, Xianyi
中科院分区：
文献类型：
--
作者：
He, Wenxiu;Mei, Qiyong;Sha, Xianyi
缺血性脑卒中治疗的一个关键问题是药物在脑缺血区的传递能力差。受4 T1癌细胞脑转移后血脑屏障（BBB）穿透能力的启发，我们设计了一种有前途的仿生纳米平台，通过将琥珀酸酐负载的pH敏感性聚合物纳米载体与4 T1细胞膜（MPP/SCB）包裹在一起，旨在促进脑缺血病变的优先靶向，以减轻缺血/再灌注损伤。在短暂性大脑中动脉闭塞（tMCAO）大鼠模型中，MPP/SCB可优先向缺血侧半球转运，是正常侧的4.79倍。此外，MPP/SCB可显著促进缺血侧脑微血管再灌注，使梗死体积减少69.9%，对tMCAO大鼠具有显著的神经保护作用，其保护效果上级优于未老化纳米载体（PP/SCB）。因此，这种设计提供了一个有前途的纳米平台，靶向脑缺血性病变的缺血性中风治疗。
The poor drug delivery to cerebral ischemic regions is a key challenge of ischemic stroke treatment. Inspired by the intriguing blood-brain barrier (BBB)-penetrating ability of 4T1 cancer cells upon their brain metastasis, we herein designed a promising biomimetic nanoplatform by camouflaging a succinobucol-loaded pH-sensitive polymeric nanovehicle with a 4T1 cell membrane (MPP/SCB), aiming to promote the preferential targeting of cerebral ischemic lesions to attenuate the ischemia/reperfusion injury. In transient middle cerebral artery occlusion (tMCAO) rat models, MPP/SCB could be preferentially delivered to the ischemic hemisphere with a 4.79-fold higher than that in the normal hemisphere. Moreover, MPP/SCB produced notable enhancement of microvascular reperfusion in the ischemic hemisphere, resulting in a 69.9% reduction of infarct volume and showing remarkable neuroprotective effects of tMCAO rats, which was superior to the counterpart uncamouflaged nanovehicles (PP/SCB). Therefore, this design provides a promising nanoplatform to target the cerebral ischemic lesions for ischemic stroke therapy.