A novel ultrasound-mediated nanodroplet-based gene delivery system for osteoporosis treatment

Angela Shar; Nadia Aboutalebianaraki; Kaylee Misiti; Yuen Yee Li Sip; Lei Zhai; Mehdi Razavi

doi:10.1016/j.nano.2022.102530

A novel ultrasound-mediated nanodroplet-based gene delivery system for osteoporosis treatment

Nanomedicine. 2022 Apr:41:102530. doi: 10.1016/j.nano.2022.102530. Epub 2022 Jan 30.

Authors

Angela Shar¹, Nadia Aboutalebianaraki², Kaylee Misiti³, Yuen Yee Li Sip⁴, Lei Zhai⁵, Mehdi Razavi⁶

Affiliations

¹ Biionix™ (Bionic Materials, Implants & Interfaces) Cluster, Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, Florida, USA; Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USA.
² Biionix™ (Bionic Materials, Implants & Interfaces) Cluster, Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, Florida, USA; Department of Material Sciences and Engineering, University of Central Florida, Orlando, Florida, USA.
³ Biionix™ (Bionic Materials, Implants & Interfaces) Cluster, Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, Florida, USA.
⁴ Department of Material Sciences and Engineering, University of Central Florida, Orlando, Florida, USA; Nanoscience Technology Center, University of Central Florida, Orlando, Florida, USA.
⁵ Nanoscience Technology Center, University of Central Florida, Orlando, Florida, USA; Department of Chemistry, University of Central Florida, Orlando, Florida, USA.
⁶ Biionix™ (Bionic Materials, Implants & Interfaces) Cluster, Department of Internal Medicine, College of Medicine, University of Central Florida, Orlando, Florida, USA; Department of Material Sciences and Engineering, University of Central Florida, Orlando, Florida, USA. Electronic address: Mehdi.Razavi@ucf.edu.

PMID: 35104672
DOI: 10.1016/j.nano.2022.102530

Abstract

This project aimed to develop, optimize, and test an ultrasound-responsive targeted nanodroplet system for the delivery of osteoporosis-related silencing gene Cathepsin K small interfering RNA (CTSK siRNA) for osteoporosis treatment. The nanodroplet (ND) is composed of a gas core made from perfluorocarbon, stabilized with albumin, encapsulated with CTSK siRNA, and embedded with alendronate (AL) for bone targeting (CTSK siRNA-ND-AL). Following the development, the responsiveness of CTSK siRNA-ND-AL to a therapeutic ultrasound probe was examined. The results of biocompatibility tests with human bone marrow-derived mesenchymal stem cells proved no significant cell death (P > 0.05). When the CTSK siRNA-ND-AL was supplemented with human osteoclast precursors, they suppressed osteoclastogenesis. Thus, this project establishes the potential of nanotechnology and ultrasound to deliver genes into the osteoclasts. This research also presents a novel ultrasound responsive and targeted nanodroplet platform that can be used as a gene and drug delivery system for various diseases including cancer.

Keywords: Nanodroplet; Osteoporosis; Targeting; Ultrasound; siRNA delivery.

Publication types

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

MeSH terms

Gene Transfer Techniques
Humans
Osteoclasts*
Osteogenesis / genetics
Osteoporosis* / drug therapy
Osteoporosis* / genetics
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism

Substances

RNA, Small Interfering