期刊
NANO LETTERS
卷 21, 期 7, 页码 3033-3043出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.1c00231
关键词
ischemic stroke; blood-brain barrier; bioinspired nanovehicle; cell membrane; drug delivery
类别
资金
- National Natural Science Foundation of China [81773201, 81873893]
- Fudan-SIMM Joint Research Fund [FU-SIMM20182005]
- PDH-SPFDU Joint Research Fund [RHJJ2018-02]
- Development Project of Shanghai Peak Disciplines-Integrative Medicine [20180101]
- Shanghai Municipal Science and Technology Major Project [2018SHZDZX01]
- ZJLab
The study presents a novel biomimetic nanoplatform designed to enhance drug delivery to cerebral ischemic lesions, demonstrating superior neuroprotective effects.
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.
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