Ischemic\nMicroenvironment-Targeted Bioinspired Lipoprotein\nSequentially Penetrates Cerebral Ischemic Lesions to Rescue Ischemic\nStroke

Reperfusion\ninjury represents a significant impediment to recovery\nafter recanalization in an ischemic stroke and can be alleviated by\nneuroprotectants. However, inadequate drug delivery to ischemic lesions\nimpairs the therapeutic effects of neuroprotectants. To address this\nissue, an ischemic microenvironment-targeted bioinspired lipoprotein\nsystem encapsulating lipoic acid (LA@PHDL) is herein designed to sequentially\npenetrate ischemic lesions and be readily taken up by neurons and\nmicroglia. In transient middle cerebral artery occlusion (tMCAO) mouse\nmodels, LA@PHDL accumulates rapidly and preferentially in the ischemic\nbrain, with a 2.29-fold higher than the nontargeted nanoplatform in\nthe early stage. Furthermore, LA@PHDL effectively restores neurological\nfunction, reduces infarct volume to 17.70%, prevents brain cell necrosis\nand apoptosis, and attenuates inflammation in tMCAO mouse models.\nThis design presents new opportunities for delivering neuroprotectants\nto cerebral ischemic lesions to improve the outcome of an ischemic\nstroke.