Injured Cardiac Tissue-Targeted Delivery of TGFβ1 siRNA by FAP Aptamer-Functionalized Extracellular Vesicles Promotes...

Area of Science:

• Cardiovascular Research
• Nanomedicine
• Gene Therapy

Background:

• Small-interfering RNA (siRNA) therapy shows promise for cardiac injury but faces challenges with stability and cellular uptake.
• Extracellular vesicles (EVs) are effective siRNA delivery systems but lack specific targeting capabilities for injured tissues.

Purpose of the Study:

• To develop an EV-based delivery system for targeted delivery of therapeutic siRNA to injured cardiac tissue.
• To investigate fibroblast activation protein (FAP) as a target for enhanced delivery to cardiac injury sites.

Main Methods:

• Fibroblast activation protein (FAP) was identified as upregulated in cardiac injury. Human serum-derived EVs (hEVs) were functionalized with a FAP-targeting aptamer to create hEV@FAP.
• hEV@FAP were loaded with TGFβ1 siRNA (siTGFβ1) and administered intravenously to angiotensin II-treated mice.

Main Results:

• FAP aptamer-functionalized EVs (hEV@FAP) demonstrated specific targeting of FAP-positive regions in vitro and in vivo.
• Administration of hEV@FAP-siTGFβ1 significantly reduced TGFβ1 expression, myocardial fibrosis, and cardiomyocyte size in mice with cardiac injury.
• The treatment improved cardiac function without causing systemic toxicity.

Conclusions:

• FAP-targeted EVs offer a novel strategy for delivering therapeutic siRNA to injured cardiac tissue.
• This approach represents a promising nanomedicine for effective cardiac repair.