Theranostics 2019; 9(23):7088-7098. doi:10.7150/thno.34895 This issue Cite

Research Paper

Ultrasound and Microbubble-targeted Delivery of a microRNA Inhibitor to the Heart Suppresses Cardiac Hypertrophy and Preserves Cardiac Function

Jonathan A. Kopechek1,2, Charles F. McTiernan1, Xucai Chen1, Jianhui Zhu1, Maureen Mburu1, Rafey Feroze1, Daniel A. Whitehurst1, Linda Lavery1, Jissy Cyriac1, Flordeliza S. Villanueva1✉

1. Center for Ultrasound Molecular Imaging and Therapeutics, Heart and Vascular Institute, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA
2. Dept. of Bioengineering, University of Louisville, Louisville, KY, USA

Citation:
Kopechek JA, McTiernan CF, Chen X, Zhu J, Mburu M, Feroze R, Whitehurst DA, Lavery L, Cyriac J, Villanueva FS. Ultrasound and Microbubble-targeted Delivery of a microRNA Inhibitor to the Heart Suppresses Cardiac Hypertrophy and Preserves Cardiac Function. Theranostics 2019; 9(23):7088-7098. doi:10.7150/thno.34895. https://www.thno.org/v09p7088.htm
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Abstract

Graphic abstract

MicroRNAs (miRs) are dysregulated in pathological left ventricular hypertrophy. AntimiR inhibition of miR-23a suppressed hypertension-induced cardiac hypertrophy in preclinical models, but clinical translation is limited by a lack of cardiac-targeted delivery systems. Ultrasound-targeted microbubble cavitation (UTMC) utilizes microbubbles as nucleic acid carriers to target delivery of molecular therapeutics to the heart. The objective of this study was to evaluate the efficacy of UTMC targeted delivery of antimiR-23a to the hearts of mice for suppression of hypertension-induced cardiac hypertrophy.

Methods: Cationic lipid microbubbles were loaded with 300 pmol negative control antimiR (NC) or antimiR-23a. Mice received continuous phenylephrine infusion via implanted osmotic minipumps, then UTMC treatments with intravenously injected antimiR-loaded microbubbles 0, 3, and 7 days later. At 2 weeks, hearts were harvested and miR-23a levels were measured. Left ventricular (LV) mass and function were assessed with echocardiography.

Results: UTMC treatment with antimiR-23a decreased cardiac miR-23a levels by 41 ± 8% compared to UTMC + antimiR-NC controls (p < 0.01). Furthermore, LV mass after 1 week of phenylephrine treatment was 17 ± 10% lower following UTMC + antimiR-23a treatment compared to UTMC + antimiR-NC controls (p = 0.02). At 2 weeks, fractional shortening was 23% higher in the UTMC + antimiR-23a mice compared to UTMC + antimiR-NC controls (p < 0.01).

Conclusions: UTMC is an effective technique for targeted functional delivery of antimiRs to the heart causing suppression of cardiac hypertrophy and preservation of systolic function. This approach could represent a revolutionary therapy for patients suffering from pathological cardiac hypertrophy and other cardiovascular conditions.

Keywords: Cardiac hypertrophy, Ultrasound targeted microbubble cavitation, miRNA delivery


Citation styles

APA
Kopechek, J.A., McTiernan, C.F., Chen, X., Zhu, J., Mburu, M., Feroze, R., Whitehurst, D.A., Lavery, L., Cyriac, J., Villanueva, F.S. (2019). Ultrasound and Microbubble-targeted Delivery of a microRNA Inhibitor to the Heart Suppresses Cardiac Hypertrophy and Preserves Cardiac Function. Theranostics, 9(23), 7088-7098. https://doi.org/10.7150/thno.34895.

ACS
Kopechek, J.A.; McTiernan, C.F.; Chen, X.; Zhu, J.; Mburu, M.; Feroze, R.; Whitehurst, D.A.; Lavery, L.; Cyriac, J.; Villanueva, F.S. Ultrasound and Microbubble-targeted Delivery of a microRNA Inhibitor to the Heart Suppresses Cardiac Hypertrophy and Preserves Cardiac Function. Theranostics 2019, 9 (23), 7088-7098. DOI: 10.7150/thno.34895.

NLM
Kopechek JA, McTiernan CF, Chen X, Zhu J, Mburu M, Feroze R, Whitehurst DA, Lavery L, Cyriac J, Villanueva FS. Ultrasound and Microbubble-targeted Delivery of a microRNA Inhibitor to the Heart Suppresses Cardiac Hypertrophy and Preserves Cardiac Function. Theranostics 2019; 9(23):7088-7098. doi:10.7150/thno.34895. https://www.thno.org/v09p7088.htm

CSE
Kopechek JA, McTiernan CF, Chen X, Zhu J, Mburu M, Feroze R, Whitehurst DA, Lavery L, Cyriac J, Villanueva FS. 2019. Ultrasound and Microbubble-targeted Delivery of a microRNA Inhibitor to the Heart Suppresses Cardiac Hypertrophy and Preserves Cardiac Function. Theranostics. 9(23):7088-7098.

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