Detection of nucleic acid-loaded microbubbles in mouse hearts during ultrasound-mediated delivery

Abstract

Heart disease is a leading cause of death worldwide. Recently, there has been a growing interest in nucleic acid-based therapeutics, such as microRNAs (miRs) or microRNA inhibitors (antimiRs), for cardiac repair. Previous studies have shown that regulating microRNA levels in the heart can promote proliferation of cardiac cells, decrease fibrosis, and improve cardiac function. Ultrasound targeted microbubble destruction (UTMD) is in development to focus the delivery of therapeutic nucleic acids to the heart and reduce adverse systemic effects. Microbubbles can be loaded with nucleic acids and exposed to ultrasound in order to induce cavitation and enhance delivery at the target site. In this study phospholipid-coated microbubbles were loaded with therapeutic miR mimics or antimiRs and injected intravenously in mice. Ultrasound pulses (2.5 MHz, 0.9 MPa peak negative pressure) were applied to the heart using a P4-1 array on a Verasonics Vantage ultrasound system. The ultrasound images were analyzed to detect microbubbles in the heart during treatment. Increased mean intensity during infusion was associated with increased delivery of nucleic acids to the heart as assessed with qPCR. The results suggest that quantitative analysis of ultrasound images to detect microbubbles in vivo may aid in monitoring UTMD treatment for improved cardiac health.