Quantum dot-engineered extracellular vesicles derived from human exfoliated deciduous teeth stem cells for the dynamic monitoring and synergistic therapy of ischemic stroke

Ischemic stroke, marked by oxidative stress and neuroinflammation in the long-term injury process after reperfusion, remains a leading global cause of disability and mortality, urging the need for innovative diagnostic and therapeutic strategies. Extracellular vesicles derived from human exfoliated deciduous teeth stem cells (SHED-EVs) have been suggested to be competent therapeutic agents in neurological diseases, with the capability as biological carriers. This study aims to develop engineered SHED-EVs for integrated diagnostic imaging and therapeutic intervention in ischemic stroke. Engineered SHED-EVs were constructed by loading fluorescent quantum dots and single-atom catalysts into native SHED-EVs. These EVs were nasally administered to middle cerebral artery occlusion (MCAO) mouse model to assess their biodistribution, blood-brain barrier (BBB) permeability, neuroprotective efficacy, functional recovery outcomes, and biocompatibility. Live imaging demonstrated preferential accumulation of engineered SHED-EVs at ischemic injury sites, correlating with dynamic BBB remodeling. Treatment significantly improved neurological function and reduced infarct volume in stroke models. Mechanistically, the engineered SHED-EVs effectively scavenged excess reactive oxygen species (ROS) and inhibited mRNA expression of proinflammation factors in oxygen-glucose deprivation (OGD)-treated brain microvessel endothelial cells (BMECs), which is critical for the restoration of BBB integrity and attenuation of neuroinflammation. We developed the engineered SHED-EVs with dual diagnostic-therapeutic functionality, which offers a promising approach for addressing post-reperfusion pathologies in ischemic stroke, including oxidative damage and neuroinflammation. The integration of tracking capability with therapeutic efficacy represents a significant advancement over current monomodal interventions. This study introduces a personalized theragnostic approach that combines SHED-EVs with real-time imaging to enhance treatment precision and monitoring in ischemic stroke. Clinically, it holds promise for improving patient outcomes by enabling early intervention, dynamic therapy adjustment, and reduced secondary injury. • Integrated SHED-EV-based diagnosis and therapy developed for ischemic stroke. • Engineered SHED-EVs preserve blood–brain barrier integrity through ROS scavenging. • Engineered SHED-EVs enable dynamic monitoring of the neurovascular barrier.