Targeting Ischemic stroke-related oxidative stress with metal nanoparticles: Mechanisms and therapeutic advances.

BACKGROUND

Ischemic stroke is a major cause of mortality and disability, largely driven by excessive reactive oxygen species (ROS) during ischemia-reperfusion injury. Current reperfusion therapies restore blood flow but fail to effectively prevent oxidative damage or promote neuronal survival.

OBJECTIVE

This review summarizes the therapeutic potential of metal-based nanoparticles (MNPs) for ischemic stroke, focusing on their catalytic antioxidant mechanisms, regulation of cellular signaling, and strategies for targeted delivery and clinical translation.

METHODS

A systematic literature search was performed following PRISMA guidelines in PubMed, Web of Science, Scopus, and Google Scholar (January 2000-March 2026). Studies investigating metal-based nanoparticles in ROS regulation, neuroprotection, and drug delivery were included, while non-metal nanomaterials, irrelevant studies, and duplicates were excluded.

RESULTS

Cerium-, manganese-, copper-, and iron-based nanoparticles exhibit enzyme-mimetic antioxidant activity by scavenging ROS and regulating oxidative stress pathways. Nanozymes and drug-loaded nanoparticles enhance neuronal survival, reduce infarction, and modulate inflammation. BBB penetration can be improved through surface functionalization, receptor-mediated transcytosis, magnetic guidance, and biomimetic coatings. MNPs also show potential as imaging agents and biomarker detectors. However, biosafety, targeting efficiency, and clinical translation remain challenges.

CONCLUSIONS

Metal-based nanoparticles are promising multifunctional platforms for ischemic stroke therapy through ROS scavenging, antioxidant pathway activation, and targeted drug delivery. Future studies should optimize nanoparticle design and validate safety and efficacy in clinical trials.