Nanoparticles Designed Based on the Blood‐Brain Barrier for the Treatment of Cerebral Ischemia‐Reperfusion Injury

Abstract Cerebral ischemia‐reperfusion injury (CI/RI) is currently considered a significant factor affecting the prognosis of ischemic stroke. The blood‐brain barrier (BBB) plays multiple roles in the treatment ofCI/RI. BBB leakage allows bloodborne toxins to exacerbate the stroke pathology. Yet as the physiological barrier that separates the blood from the brain, BBB also poses a significant obstacle to therapeutic drug delivery. Therefore, it is essential to consider both crossing and repairing the BBB in the process of the treatment of CI/RI. Leveraging the exceptional benefits of nanoparticles (NPs) for BBB penetration and targeted repair, numerous NPs are developed as promising drug delivery platforms. Considering the complex role of the BBB in CI/RI, this review delves into the strategies for designing NPs to cross the BBB, focusing on peptide‐modified NPs, cell‐mediated NPs, cell membrane‐derived NPs, and BBB‐modulating NPs. Additionally, it summarizes design strategies of NPs targeting endothelial cells (ECs), astrocytes, and those aimed at regulating the microenvironment to repair the BBB. On this basis, it reveals the prospects and challenges of NPs designed around the BBB in CI/RI treatment. And it highlights the need to combine BBB permeability promotion and BBB repair in nanoparticle strategies designed based on the BBB to achieve more effective treatment.