Ultrasound-Targeted Microbubble Destruction Mediates Gene Transfection for Beta-Cell Regeneration and Glucose Regulation

Chao Zhang; Shuyuan Chen; Qunying Li; Jiao Wu; Fuqiang Qiu; Zhiyi Chen; Yang Sun; Jieli Luo; Raul A Bastarrachea; Paul A Grayburn; Ralph A DeFronzo; Yajing Liu; Kun Qian; Pintong Huang

doi:10.1002/smll.202008177

Ultrasound-Targeted Microbubble Destruction Mediates Gene Transfection for Beta-Cell Regeneration and Glucose Regulation

Small. 2021 Aug;17(31):e2008177. doi: 10.1002/smll.202008177. Epub 2021 Jun 29.

Authors

Chao Zhang^{1

2}, Shuyuan Chen³, Qunying Li^{1

2}, Jiao Wu⁴, Fuqiang Qiu^{1

2}, Zhiyi Chen⁵, Yang Sun^{1

2}, Jieli Luo^{1

2}, Raul A Bastarrachea⁶, Paul A Grayburn⁷, Ralph A DeFronzo⁸, Yajing Liu^{1

2}, Kun Qian⁴, Pintong Huang^{1

2}

Affiliations

¹ Department of Ultrasound and Research Center of Ultrasound in Medicine and Biomedical Engineering, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.
² Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, China.
³ Department of Internal Medicine, UT Southwestern medical center at Dallas, Dallas, TX, 75390, USA.
⁴ School of Biomedical Engineering, Institute of Medical Robotics and Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, 200030, China.
⁵ Department of Ultrasound Medicine, Laboratory of Ultrasound Molecular Imaging, The Third Affiliated Hospital of Guangzhou Medical University, Guangdong, 510000, China.
⁶ Southwest National Primate Research Center, San Antonio, TX, 78249, USA.
⁷ Department of Internal Medicine, Division of Cardiology, Baylor Heart and Vascular Institute, Baylor University Medical Center, 621 N. Hall St, Suite H030, Dallas, Texas, 75226, USA.
⁸ Department of Medicine, Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, University Health System, San Antonio, TX, 78229, USA.

PMID: 34185956
DOI: 10.1002/smll.202008177

Abstract

Ultrasound-targeted microbubble destruction (UTMD) mediates gene transfection with high biosafety and thus has been promising toward treatment of type 1 diabetes. However, the potential application of UTMD in type 2 diabetes (T2D) is still limited, due to the lack of systematic design and dynamic monitoring. Herein, an efficient gene delivery system is constructed by plasmid deoxyribonucleic acid (DNA) encoding glucagon-like peptide 1 (GLP-1) in ultrasound-induced microbubbles, toward treatment of T2D in macaque. The as designed UTMD afforded enhancement of cell membrane penetration and GLP-1 expression in macaque, which is characterized by ultrasound-guided biopsy to monitor the dynamic process of islet cells for 6 months. Also, improvement of pancreatic beta cell regeneration, and regulation of plasma glucose in macaque with T2D is achieved. The approach would serve as promising alternatives for the treatment of T2D.

Keywords: cell metabolism; diabetes; gene transfection; microbubbles; ultrasound.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 2*
Gene Transfer Techniques
Glucose
Humans
Insulin-Secreting Cells*
Microbubbles
Regeneration
Transfection

Substances

Glucose