Ultrasound-Guided Functionalized Extracellular Vesicles for Visualized, Controlled, and Efficient Renal Delivery for...

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Nanotechnology

Background:

• Mesenchymal stem cell-derived extracellular vesicles (EVs) show therapeutic potential for acute kidney injury (AKI).
• Inefficient delivery and reduced cellular uptake limit the efficacy of EVs in AKI treatment.
• Cisplatin-induced damage in AKI impairs renal tubular cell uptake of EVs.

Purpose of the Study:

• To engineer ultrasound-guided, microbubble-functionalized EVs (MB-EVs) for enhanced renal delivery and uptake in AKI.
• To visualize and control EV delivery using ultrasound-triggered release.
• To investigate the role of F-actin in MB-EV uptake and therapeutic efficacy.

Main Methods:

• Development of RGD-integrin functionalized MB-EVs for targeted delivery.
• Percutaneous intrarenal injection of MB-EVs with ultrasound guidance.
• Assessment of EV uptake pathways, F-actin restoration, and therapeutic effects in an AKI model.
• Analysis of renal function, morphology, apoptosis, and mitochondrial integrity.

Main Results:

• Ultrasound imaging enabled precise localization and triggered microbubble-mediated release of MB-EVs.
• MB-EVs restored F-actin, enhancing endocytic pathways and improving EV uptake in cisplatin-damaged renal cells.
• MB-EVs demonstrated superior recovery of renal function, morphology, and mitochondrial health compared to EVs alone.
• EVs delivered miR-24-3p, restoring CPT1A-mediated fatty acid oxidation for improved renal recovery.

Conclusions:

• Engineered ultrasound-guided MB-EVs offer visualized, controlled, and efficient renal delivery for AKI treatment.
• MB-EVs overcome cisplatin-induced uptake barriers by restoring F-actin.
• This approach achieves superior therapeutic outcomes, presenting a promising strategy for AKI management.