Ischemic stroke remains a leading global cause of disability and mortality, and a major challenge in stroke treatment is "reperfusion injury"—where return of blood flow causes oxidative stress and inflammation, further damaging the brain and disrupting the blood-brain barrier (BBB). Current diagnostic imaging and therapeutic treatment are often separate processes, delaying the critical feedback clinicians need to assess how well a treatment is working in real-time.
In a new study published in Translational Dental Research, a team of researchers from China introduced a "theragnostic" agent that combines therapy and diagnosis.
"We engineered extracellular vesicles derived from human exfoliated deciduous teeth stem cells (SHED-EVs)," shares co-corresponding author Lingxin Zhu. "These vesicles were loaded with manganese-based single-atom catalysts and near-infrared quantum dots (Mn/QD SACs) for integrated diagnostic imaging and therapeutic intervention in ischemic stroke."
"The unique advantage of SHED-EVs lies in their lineage affinity to neural cells, making them effective carriers for delivering neuroprotective agents directly to injured brain tissue.," adds co-corresponding author Gang Chen. "By incorporating quantum dots, the researchers endowed these vesicles with fluorescence capabilities in the near-infrared spectrum, allowing for deep-tissue imaging without interference from the body's natural fluorescence."
The team found that in mouse models of stroke, the engineered EVs demonstrated a dual capability of dynamic monitoring and synergistic therapy. "Upon intranasal administration, the EVs preferentially accumulated at the site of ischemic injury," adds Zhu.
The quantum dots allowed to visualize the dynamic remodeling of the blood-brain barrier in real-time, tracking the restoration of vascular integrity. In addition, the engineered vesicles effectively scavenged excess reactive oxygen species (ROS) and inhibited pro-inflammatory factors.
"The treatment was also shown to increase the expression of GPX4, a protein that protects cells from ferroptosis," says Zhu. "This significantly reduced the volume of the infarction and improved neurological function and motor skills in the treated mice."
The integration of tracking capability with therapeutic efficacy represents an advancement over current monomodal interventions.
"This personalized approach holds clinical promise for improving patient outcomes by enabling early intervention and dynamic therapy adjustment based on real-time imaging feedback," notes Zhu.
