Enhanced Local Delivery of microRNA-145a-5P into Mouse Aorta via Ultrasound-Targeted Microbubble Destruction Inhibits Atherosclerotic Plaque Formation

Abstract

Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play a key role in the formation and rupture of atherosclerotic plaques. Previous studies have confirmed that microRNA-145 (miR-145) is involved in the phenotypic regulation of VSMCs and reduction of atherosclerosis. At present, seeking safe and effective gene delivery remains a key problem restricting the development of gene therapy. In recent years, ultrasound-targeted microbubble destruction (UTMD) has become a safe and effective transfection method that is widely used in the basic research of gene therapy for heart and tumor diseases. Here, we synthesized cationic microbubbles to encapsulate miR-145 and targeted their release into VSMCs in vitro and in vivo using ultrasound. The feasibility of this gene therapy was verified by fluorescence microscopy and an in vivo imaging system. The results showed that treatment with miR-145 delivered via UTMD considerably improved the gene transfection efficiency and promoted the contraction phenotype of VSMCs in vitro. In vivo, this treatment reduced the atherosclerotic plaque area by 48.04% compared with treatment with free miR-145. Therefore, UTMDmediated miRNA therapy may provide a new targeted therapeutic approach for atherosclerotic plaques.

Ultrasound Microbubble-Stimulated miR-145-5p Inhibits Malignant Behaviors of Breast Cancer Cells by Targeting ACTG1

“…Ultrasound-targeted microbubble destruction–mediated miR-145-5p therapy was once demonstrated to be effective for atherosclerotic plaques. In the study performed by Wu et al, 42 cationic MBs encapsulating miR-145-5p were synthesized, and ultrasound was used to target their release into vascular smooth muscle cells, the method of which were confirmed to better suppress abnormal vascular smooth muscle cell growth and migration in vitro and reduce the atherosclerotic plaque area in vivo than treatment with free miR-145-5p. Herein, we discovered that UTMD delivery enhanced the overexpression efficiency of miR-145-5p, and gain-of-function assays showed that UTMD-delivered miR-145-5p mimics reinforced the repression of miR-145-5p on BC cell malignant behaviors.…”

Non-coding RNAs are key players and promising therapeutic targets in atherosclerosis

“…Yu Wu et al synthesized cationic microbubbles and encapsulated miR-145 within them to target its release in vascular smooth muscle cells using ultrasound. The in vitro findings demonstrated that this approach significantly increased the transfection efficiency of miR-145; in vivo, this approach reduced AS plaque size by nearly half that achieved by direct treatment with free miR-145 (Wu et al, 2023). In addition, UTMD technology can be applied to exosomal vectors to achieve targeted release of the mounted ncRNA (Sun et al, 2020).…”