Preferential Targeting Cerebral Ischemic Lesions with Cancer Cell-Inspired Nanovehicle for Ischemic Stroke Treatment

• Published in: Nano letters 2021-04, Vol.21 (7), p.3033-3043
• Main Authors: He, Wenxiu, Mei, Qiyong, Li, Jie, Zhai, Yuting, Chen, Yiting, Wang, Rui, Lu, Enhao, Zhang, Xiao-Yong, Zhang, Zhiwen, Sha, Xianyi
• Format: Article
• Language: English
• ISSN: 1530-6984; 1530-6992
• DOI: 10.1021/acs.nanolett.1c00231

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.