A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system

Shaowei Wang,1 Xiaochun Wei,1 Xiaojuan Sun,1 Chongwei Chen,1 Jingming Zhou,2 Ge Zhang,3 Heng Wu,3 Baosheng Guo,3 Lei Wei1,2 1Department of Orthopaedics, The 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi, China; 2Department of Orthopaedics, Rhode Island Hospital, The Warren Alpert Medic...

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Autores principales:	Wang S, Wei X, Sun X, Chen C, Zhou J, Zhang G, Wu H, Guo B, Wei L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	cartilage diseases lipid nanoparticle RNA interference delivery system Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/379e489ad779407a91929c3e03eebc53
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spelling	oai:doaj.org-article:379e489ad779407a91929c3e03eebc532021-12-02T07:47:01ZA novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system1178-2013https://doaj.org/article/379e489ad779407a91929c3e03eebc532018-01-01T00:00:00Zhttps://www.dovepress.com/a-novel-therapeutic-strategy-for-cartilage-diseases-based-on-lipid-nan-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Shaowei Wang,1 Xiaochun Wei,1 Xiaojuan Sun,1 Chongwei Chen,1 Jingming Zhou,2 Ge Zhang,3 Heng Wu,3 Baosheng Guo,3 Lei Wei1,2 1Department of Orthopaedics, The 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi, China; 2Department of Orthopaedics, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA; 3Integrated Traditional Chinese and Western Medicine, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Background: Cartilage degeneration affects millions of people but preventing its degeneration is a big challenge. Although RNA interference (RNAi) has been used in human trials via silencing specific genes, the cartilage RNAi has not been possible to date because the cartilage is an avascular and very dense tissue with very low permeability. Purpose: The objective of this study was to develop and validate a novel lipid nanoparticle (LNP)-siRNA delivery system that can prevent cartilage degeneration by knocking down specific genes. Methods: LNP transfection efficiency was evaluated in vitro and ex vivo. Indian Hedgehog (Ihh) has been correlated with cartilage degeneration. The in vivo effects of LNP-Ihh siRNA complexes on cartilage degeneration were evaluated in a rat model of surgery-induced osteoarthritis (OA). Results: In vitro, 100% of chondrocytes were transfected with siRNA in the LNP-siRNA group. In accordance with the cell culture results, red positive signals could be detected even in the deep layer of cartilage tissue cultures treated by LNP-beacon. In vivo data showed that LNP is specific for cartilage, since positive signals were detected by fluorescence molecular tomography and confocal microscopy in joint cartilage injected with LNP-beacon, but not on the surface of the synovium. In the rat model of OA, intraarticular injection of LNP-Ihh siRNA attenuated OA progression, and PCR results showed LNP-Ihh siRNA exerted a positive impact on anabolic metabolism and negative impact on catabolic metabolism. Conclusion: This study demonstrates that our LNP-RNAi delivery system has a significantly chondroprotective effect that attenuates cartilage degeneration and holds great promise as a powerful tool for treatment of cartilage diseases by knocking down specific genes. Keywords: cartilage diseases, lipid nanoparticle, RNA interference, delivery systemWang SWei XSun XChen CZhou JZhang GWu HGuo BWei LDove Medical Pressarticlecartilage diseaseslipid nanoparticleRNA interferencedelivery systemMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 617-631 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	cartilage diseases lipid nanoparticle RNA interference delivery system Medicine (General) R5-920
spellingShingle	cartilage diseases lipid nanoparticle RNA interference delivery system Medicine (General) R5-920 Wang S Wei X Sun X Chen C Zhou J Zhang G Wu H Guo B Wei L A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system
description	Shaowei Wang,1 Xiaochun Wei,1 Xiaojuan Sun,1 Chongwei Chen,1 Jingming Zhou,2 Ge Zhang,3 Heng Wu,3 Baosheng Guo,3 Lei Wei1,2 1Department of Orthopaedics, The 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi, China; 2Department of Orthopaedics, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, RI, USA; 3Integrated Traditional Chinese and Western Medicine, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong Background: Cartilage degeneration affects millions of people but preventing its degeneration is a big challenge. Although RNA interference (RNAi) has been used in human trials via silencing specific genes, the cartilage RNAi has not been possible to date because the cartilage is an avascular and very dense tissue with very low permeability. Purpose: The objective of this study was to develop and validate a novel lipid nanoparticle (LNP)-siRNA delivery system that can prevent cartilage degeneration by knocking down specific genes. Methods: LNP transfection efficiency was evaluated in vitro and ex vivo. Indian Hedgehog (Ihh) has been correlated with cartilage degeneration. The in vivo effects of LNP-Ihh siRNA complexes on cartilage degeneration were evaluated in a rat model of surgery-induced osteoarthritis (OA). Results: In vitro, 100% of chondrocytes were transfected with siRNA in the LNP-siRNA group. In accordance with the cell culture results, red positive signals could be detected even in the deep layer of cartilage tissue cultures treated by LNP-beacon. In vivo data showed that LNP is specific for cartilage, since positive signals were detected by fluorescence molecular tomography and confocal microscopy in joint cartilage injected with LNP-beacon, but not on the surface of the synovium. In the rat model of OA, intraarticular injection of LNP-Ihh siRNA attenuated OA progression, and PCR results showed LNP-Ihh siRNA exerted a positive impact on anabolic metabolism and negative impact on catabolic metabolism. Conclusion: This study demonstrates that our LNP-RNAi delivery system has a significantly chondroprotective effect that attenuates cartilage degeneration and holds great promise as a powerful tool for treatment of cartilage diseases by knocking down specific genes. Keywords: cartilage diseases, lipid nanoparticle, RNA interference, delivery system
format	article
author	Wang S Wei X Sun X Chen C Zhou J Zhang G Wu H Guo B Wei L
author_facet	Wang S Wei X Sun X Chen C Zhou J Zhang G Wu H Guo B Wei L
author_sort	Wang S
title	A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system
title_short	A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system
title_full	A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system
title_fullStr	A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system
title_full_unstemmed	A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system
title_sort	novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-rnai delivery system
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/379e489ad779407a91929c3e03eebc53
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A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system

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