一种新型超声介导的基于纳升级液滴的基因传递系统，用于骨质疏松症治疗。

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

机构信息

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.

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.

出版信息

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

DOI:10.1016/j.nano.2022.102530

PMID:35104672

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.

摘要

本项目旨在开发、优化和测试一种超声响应靶向纳米液滴系统，用于递送与骨质疏松症相关的组织蛋白酶 K 小干扰 RNA（CTSK siRNA），以治疗骨质疏松症。纳米液滴（ND）由全氟碳气体核组成，用白蛋白稳定，包裹 CTSK siRNA，并嵌入阿仑膦酸钠（AL）用于骨靶向（CTSK siRNA-ND-AL）。在开发之后，研究了 CTSK siRNA-ND-AL 对治疗性超声探头的响应性。与人骨髓间充质干细胞的生物相容性测试结果表明，细胞没有明显死亡（P > 0.05）。当 CTSK siRNA-ND-AL 补充人破骨细胞前体时，它们抑制了破骨细胞的生成。因此，本项目确立了纳米技术和超声将基因递送入破骨细胞的潜力。这项研究还提出了一种新型的超声响应和靶向纳米液滴平台，可作为包括癌症在内的各种疾病的基因和药物递送系统。