title: Ultrasound and microbubble-induced local delivery of MicroRNA-based therapeutics.
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.
authors.affiliation: Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: R.kwekkeboom@vumc.nl.
authors.forename: Rick F J
authors.initials: RF
authors.lastname: Kwekkeboom
authors.affiliation: Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lei
authors.affiliation: Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Sylvia J P
authors.initials: SJ
authors.lastname: Bogaards
authors.affiliation: Axle International, The Hague, The Netherlands; Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Aiazian
authors.affiliation: Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Otto
authors.initials: O
authors.lastname: Kamp
authors.affiliation: Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Paulus
authors.affiliation: Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Joost P G
authors.initials: JP
authors.lastname: Sluijter
authors.affiliation: Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: René J P
authors.initials: RJ
authors.lastname: Musters
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics*; D045423:Microbubbles; D018482:Muscle, Skeletal / Q000502:physiology*; D015612:Phonophoresis / Q000379:methods*; D013010:Sonication / Q000379:methods; D014162:Transfection / Q000379:methods*
chemical_list: D035683:MicroRNAs
keywords: AntagomiR; AntimiR; Drug delivery; Endothelial cells; MicroRNA; Microbubbles; Ultrasound