Nanomaterial-Based Drug Delivery Systems for Ischemic Stroke: From Blood-Brain Barrier Crossing to Neuroprotection

Yanan He,1,* Mengyao Qu,1,* Lu Yu,1,* Yiuxn Lu,1 Jin Hong,1 Miao Sun,1 Huikai Yang,1 Weidong Mi,1 Hang Guo,2 Yulong Ma1 1Department of Anesthesiology, the First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Anesthesiology, the Seventh Medical Center of Chinese PLA General Hospital, Beijing, 100700, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yulong Ma, Email yulongma123@163.com Weidong Mi, Email wwdd1962@163.comAbstract: Ischemic stroke remains a leading cause of mortality and long-term disability worldwide, largely due to limited therapeutic options and the restrictive nature of the blood–brain barrier (BBB). Nanomaterial-based drug delivery systems have emerged as promising strategies to enhance brain-targeted therapy by facilitating BBB penetration and enabling multi-pathway neuroprotection. This review provides a mechanism-driven overview of recent advances in stroke nanomedicine, classifying nanotherapeutic strategies into four major categories: reactive oxygen species–scavenging nanomaterials, glutamate-modulating systems, anti-inflammatory nanocarriers, and neuroprotective or neuroregenerative delivery platforms. Representative nanoplatforms within each category are discussed with respect to their BBB-crossing mechanisms, therapeutic potential, and translational relevance. In addition, the current clinical trial landscape, key translational bottlenecks, and emerging artificial intelligence–assisted approaches for optimizing nanocarrier design and supporting translational decision-making are highlighted. Overall, this review aims to provide a structured, clinically oriented framework to guide the rational design and translational development of nanomaterial-based drug delivery systems for ischemic stroke.Keywords: ischemic stroke, nanomedicine, blood-brain barrier, neuroprotection, drug delivery