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

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.