Key Laboratory of Smart Drug Delivery, School of Pharmacy, Fudan University, Shanghai 201203, China.
Department of Neurosurgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
Nano Lett. 2021 Apr 14;21(7):3033-3043. doi: 10.1021/acs.nanolett.1c00231. Epub 2021 Mar 23.
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.
向脑缺血区域的药物递送不良是缺血性脑卒中治疗的一个关键挑战。受在脑转移时具有令人感兴趣的穿透血脑屏障（BBB）能力的 4T1 癌细胞的启发，我们设计了一种有前途的仿生纳米平台，通过用负载琥珀酸舒马曲坦的 pH 敏感聚合物纳米载体伪装 4T1 细胞膜（MPP/SCB），旨在促进对脑缺血损伤的选择性靶向，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 可以优先递送到缺血侧半球，其在正常侧半球的分布是其 4.79 倍。此外，MPP/SCB 可显著增强缺血侧半球的微血管再灌注，使梗死体积减少 69.9%，并显示出对 tMCAO 大鼠的显著神经保护作用，优于未伪装的纳米载体（PP/SCB）。因此，该设计为针对缺血性脑卒中治疗的脑缺血损伤提供了一种有前途的纳米平台。
