Ultrasound and Microbubble-Induced Local Delivery of MicroRNA-Based Therapeutics

• Published in: Ultrasound in medicine & biology Vol. 41; no. 1; pp. 163 - 176
• Main Authors: Kwekkeboom, Rick F.J, Lei, Zhiyong, Bogaards, Sylvia J.P, Aiazian, Eric, Kamp, Otto, Paulus, Walter J, Sluijter, Joost P.G, Musters, René J.P
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.01.2015
• Subjects: Animals; AntagomiR; AntimiR; Cells, Cultured; Drug delivery; Endothelial cells; Endothelial Cells - physiology; Humans; Male; Mice; Mice, Inbred C57BL; Microbubbles; MicroRNA; MicroRNAs - administration & dosage; MicroRNAs - genetics; Muscle, Skeletal - physiology; Phonophoresis - methods; Radiology; Sonication - methods; Transfection - methods; Ultrasound; MicroRNA; Microbubbles; AntimiR; Drug delivery; Ultrasound; AntagomiR; Endothelial cells
• ISSN: 0301-5629; 1879-291X
• DOI: 10.1016/j.ultrasmedbio.2014.08.012

Abstract MicroRNAs are involved in many pathologic processes and are a promising target for therapeutic intervention. However, successful, localized delivery of microRNA-based therapeutics is lacking. In this study, cationic ultrasound-responsive microbubbles (MBs) were used to deliver microRNA blockers and mimics in vitro and in vivo . Cationic MBs successfully delivered microRNA blockers to human endothelial cells on ultrasound (US) exposure in vitro . This in vitro US protocol did not successfully deliver microRNA mimics to skeletal muscle of mice, whereas an US protocol that is routinely used for contrast imaging did. Additionally, we used cationic MBs and US to locally deliver antimiR and antagomiR molecules with US causing inertial cavitation. Delivery of antimiR to the extracellular compartments of the muscle was only slightly increased, whereas delivery of antagomiR to the capillaries, myocytes and extracellular space was significantly increased. AntagomiR seems to be a more suitable microRNA blocker than antimiR for use in combination with MBs and US for local delivery.