Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Ministry of Education), Shanghai 201203, China.
Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai 200030, China.
ACS Appl Mater Interfaces. 2024 Sep 18;16(37):49628-49639. doi: 10.1021/acsami.4c08966. Epub 2024 Sep 3.
Reperfusion injury represents a significant impediment to recovery after recanalization in an ischemic stroke and can be alleviated by neuroprotectants. However, inadequate drug delivery to ischemic lesions impairs the therapeutic effects of neuroprotectants. To address this issue, an ischemic microenvironment-targeted bioinspired lipoprotein system encapsulating lipoic acid (LA@PHDL) is herein designed to sequentially penetrate ischemic lesions and be readily taken up by neurons and microglia. In transient middle cerebral artery occlusion (tMCAO) mouse models, LA@PHDL accumulates rapidly and preferentially in the ischemic brain, with a 2.29-fold higher than the nontargeted nanoplatform in the early stage. Furthermore, LA@PHDL effectively restores neurological function, reduces infarct volume to 17.70%, prevents brain cell necrosis and apoptosis, and attenuates inflammation in tMCAO mouse models. This design presents new opportunities for delivering neuroprotectants to cerebral ischemic lesions to improve the outcome of an ischemic stroke.
再灌注损伤是缺血性脑卒中再通后恢复的一个重大障碍，可以通过神经保护剂来缓解。然而，神经保护剂向缺血性病变的药物递送不足会影响其治疗效果。为了解决这个问题，本文设计了一种缺血微环境靶向仿生脂蛋白系统，将硫辛酸（LA@PHDL）包裹其中，以顺序穿透缺血性病变，并被神经元和小胶质细胞轻易摄取。在短暂性大脑中动脉闭塞（tMCAO）小鼠模型中，LA@PHDL 迅速且优先地在缺血性大脑中积累，早期的积累量是无靶向纳米平台的 2.29 倍。此外，LA@PHDL 有效地恢复了神经功能，将梗死体积减少到 17.70%，防止了脑细胞坏死和凋亡，并减轻了 tMCAO 小鼠模型中的炎症。本设计为将神经保护剂递送到脑缺血性病变提供了新的机会，以改善缺血性脑卒中的预后。
