Nanoparticles in the Diagnosis and Management of Stroke: A Review

Stroke is the third leading cause of death and the fourth leading cause of disability-adjusted life years worldwide, yet disease-modifying treatment remains largely confined to reperfusion of large-vessel ischemic occlusion within a narrow window. No neuroprotective or hemostatic agent has entered routine practice. Engineered nanoparticles have been proposed to improve delivery across the blood-brain barrier, concentrate drug within the ischemic or perihematomal microenvironment, and add imaging or sensing functions. The resulting literature is large but fragmented across platforms, models, and outcome measures, so it is not evident which platforms carry the strongest evidence or which are closest to clinical evaluation. This narrative review synthesizes preclinical and clinical evidence on nanoparticle-based diagnosis, treatment, rehabilitation, and monitoring in ischemic and hemorrhagic stroke. We searched PubMed, Scopus, and the Cochrane Library from inception to July 2025 using predefined Boolean strings and assigned each included study an evidence tier to separate extrapolated and cross-field evidence from stroke-specific data. Comparative tables summarize nanoparticle type, payload, model, route, dose, treatment window, particle size and surface charge, principal outcomes, safety assessment, and translational readiness. Therapeutic evidence is almost entirely preclinical: Efficacy has been shown in young, male, comorbidity-free rodents treated within minutes of reperfusion and followed for 24 h to 28 days, with group sizes typically between three and 15, and few studies reporting any bleeding or coagulation endpoint. Diagnostic applications are closer to patients because iron-oxide nanoparticles have already been given to humans, although not for imaging. We identified seven registered clinical studies of nanoparticle-related interventions in stroke; one perfluorocarbon nanodroplet emulsion completed a randomized dose-escalation trial in acute ischemic stroke, the EU Clinical Trials Register returned none, and none exists in hemorrhagic stroke. Nanoparticle platforms, therefore, remain investigational, and progress will depend less on new chemistry than on comorbid and large-animal models, realistic treatment windows, systematic reporting of bleeding risk and of interference with follow-up imaging, and reproducible manufacturing.