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Introduction to the Ultrasound Targeted Microbubble Destruction Technique
Published on: June 12, 2011
Ultrasound and microbubble-induced local delivery of MicroRNA-based therapeutics
Rick F J Kwekkeboom1, Zhiyong Lei2, Sylvia J P Bogaards1
1Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands.
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.
Insights
Cationic microbubbles with ultrasound effectively deliver microRNA blockers in vitro and in vivo. AntagomiR molecules showed superior local delivery to muscle tissues compared to antimiR, indicating their potential for targeted microRNA therapeutics.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Pharmacology
Background:
- MicroRNAs play crucial roles in various pathological processes.
- Targeted delivery of microRNA therapeutics remains a significant challenge.
- MicroRNA-based therapies offer promising therapeutic potential.
Purpose of the Study:
- To evaluate the efficacy of cationic ultrasound-responsive microbubbles (MBs) for localized microRNA delivery.
- To compare the delivery efficiency of microRNA blockers and mimics in vitro and in vivo.
- To determine the optimal ultrasound (US) protocol and microRNA blocker for targeted delivery.
Main Methods:
- Utilized cationic ultrasound-responsive microbubbles (MBs) for targeted delivery of microRNA blockers and mimics.
- Investigated in vitro delivery to human endothelial cells using ultrasound exposure.
- Assessed in vivo delivery to mouse skeletal muscle using different US protocols and microRNA blockers (antimiR, antagomiR).
- Analyzed delivery efficiency to various cellular and extracellular compartments within the muscle.
Main Results:
- Cationic MBs successfully delivered microRNA blockers to endothelial cells in vitro with ultrasound.
- An ultrasound protocol used for contrast imaging, not the in vitro protocol, enabled microRNA mimic delivery to mouse skeletal muscle.
- Ultrasound-induced inertial cavitation with MBs significantly enhanced antagomiR delivery to capillaries, myocytes, and extracellular space.
- AntagomiR delivery was significantly improved compared to antimiR delivery.
Conclusions:
- Cationic microbubbles combined with ultrasound represent a viable strategy for localized microRNA delivery.
- AntagomiR is a more effective microRNA blocker than antimiR for ultrasound-mediated delivery to skeletal muscle.
- Optimized ultrasound protocols are critical for successful microRNA mimic and blocker delivery.
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