Co-Delivery Of Dihydroartemisinin And HMGB1 siRNA By TAT-Modified Cationic Liposomes Through The TLR4 Signaling Pathway For Treatment Of Lupus Nephritis

Lu Diao,1,2 Jin Tao,2 Yiqi Wang,3 Ying Hu,1,2 Wenfei He1 1School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of China; 2College of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, Zhejiang 315100, People’s Republic of Chin...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Diao L, Tao J, Wang Y, Hu Y, He W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	cationic liposome hmgb1 sirna dha toll-like receptor 4 Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5e921dc9440d484487aac485f1e287f4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5e921dc9440d484487aac485f1e287f4
record_format	dspace
spelling	oai:doaj.org-article:5e921dc9440d484487aac485f1e287f42021-12-02T09:22:35ZCo-Delivery Of Dihydroartemisinin And HMGB1 siRNA By TAT-Modified Cationic Liposomes Through The TLR4 Signaling Pathway For Treatment Of Lupus Nephritis1178-2013https://doaj.org/article/5e921dc9440d484487aac485f1e287f42019-11-01T00:00:00Zhttps://www.dovepress.com/co-delivery-of-dihydroartemisinin-and-hmgb1-sirna-by-tat-modified-cati-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Lu Diao,1,2 Jin Tao,2 Yiqi Wang,3 Ying Hu,1,2 Wenfei He1 1School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of China; 2College of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, Zhejiang 315100, People’s Republic of China; 3College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, People’s Republic of ChinaCorrespondence: Ying HuCollege of Pharmacy, Zhejiang Pharmaceutical College, No. 888, East Section, Yinxian Main Road, The Zone of Higher Education, Ningbo, Zhejiang 315100, People’s Republic of ChinaTel +86 5748822 2707Fax +86 5748822 3023Email pharmhawk@126.comWenfei HeSchool of Pharmaceutical Sciences, Wenzhou Medical University, Ouhai District, Chashan Street, University Campus, Wenzhou, Zhejiang 325035 People’s Republic of ChinaTel +86 0577 86699572Email wenfeihe@126.comBackground and purpose: Systemic lupus erythematous (SLE) is an autoimmune disease caused by many factors. Lupus nephritis (LN) is a common complication of SLE and represents a major cause of morbidity and mortality. Previous studies have shown the advantages of multi-targeted therapy for LN and that TLR4 signaling is a target of anti-LN drugs. High-mobility group box 1 (HMGB1), a nuclear protein with a proinflammatory cytokine activity, binds specifically to TLR4 to induce inflammation. We aimed to develop PEGylated TAT peptide-cationic liposomes (TAT-CLs) to deliver anti-HMGB1 siRNA and dihydroartemisinin (DHA) to increase LN therapeutic efficiency and explore their treatment mechanism.Methods: We constructed the TAT-CLs-DHA/siRNA delivery system using the thin film hydration method. The uptake and localization of Cy3-labeled siRNA were detected by confocal microscopy and flow cytometry. MTT assays were used to detect glomerular mesangial cell proliferation. Real-time PCR, Western blot analysis, and ELISA evaluated the anti-inflammatory mechanism of TAT-CLs-DHA/siRNA.Results: We constructed the TAT-CLs-DHA/siRNA delivery system measuring approximately 140 nm with superior storage and serum stabilities. In vitro, it showed significantly greater uptake compared with unmodified liposomes and significant inhibition of glomerular mesangial cell proliferation. TAT-CLs-DHA/siRNA inhibited NF-κB activation in a concentration-dependent manner. Real-time PCR and Western blot analysis showed that TAT-CLs-DHA/siRNA downregulated expression of HMGB1 mRNA and protein. TAT-CLs-DHA/siRNA markedly diminished Toll-like receptor 4 (TLR4) expression and subsequent activation of MyD88, IRAK4, and NF-κB.Conclusion: TAT-CLs-DHA/siRNA may have the potential for treatment of inflammatory diseases such as LN mediated by the TLR4 signaling pathway.Keywords: cationic liposome, HMGB1 siRNA, DHA, Toll-like receptor 4Diao LTao JWang YHu YHe WDove Medical Pressarticlecationic liposomehmgb1 sirnadhatoll-like receptor 4Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 8627-8645 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	cationic liposome hmgb1 sirna dha toll-like receptor 4 Medicine (General) R5-920
spellingShingle	cationic liposome hmgb1 sirna dha toll-like receptor 4 Medicine (General) R5-920 Diao L Tao J Wang Y Hu Y He W Co-Delivery Of Dihydroartemisinin And HMGB1 siRNA By TAT-Modified Cationic Liposomes Through The TLR4 Signaling Pathway For Treatment Of Lupus Nephritis
description	Lu Diao,1,2 Jin Tao,2 Yiqi Wang,3 Ying Hu,1,2 Wenfei He1 1School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, People’s Republic of China; 2College of Pharmacy, Zhejiang Pharmaceutical College, Ningbo, Zhejiang 315100, People’s Republic of China; 3College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, People’s Republic of ChinaCorrespondence: Ying HuCollege of Pharmacy, Zhejiang Pharmaceutical College, No. 888, East Section, Yinxian Main Road, The Zone of Higher Education, Ningbo, Zhejiang 315100, People’s Republic of ChinaTel +86 5748822 2707Fax +86 5748822 3023Email pharmhawk@126.comWenfei HeSchool of Pharmaceutical Sciences, Wenzhou Medical University, Ouhai District, Chashan Street, University Campus, Wenzhou, Zhejiang 325035 People’s Republic of ChinaTel +86 0577 86699572Email wenfeihe@126.comBackground and purpose: Systemic lupus erythematous (SLE) is an autoimmune disease caused by many factors. Lupus nephritis (LN) is a common complication of SLE and represents a major cause of morbidity and mortality. Previous studies have shown the advantages of multi-targeted therapy for LN and that TLR4 signaling is a target of anti-LN drugs. High-mobility group box 1 (HMGB1), a nuclear protein with a proinflammatory cytokine activity, binds specifically to TLR4 to induce inflammation. We aimed to develop PEGylated TAT peptide-cationic liposomes (TAT-CLs) to deliver anti-HMGB1 siRNA and dihydroartemisinin (DHA) to increase LN therapeutic efficiency and explore their treatment mechanism.Methods: We constructed the TAT-CLs-DHA/siRNA delivery system using the thin film hydration method. The uptake and localization of Cy3-labeled siRNA were detected by confocal microscopy and flow cytometry. MTT assays were used to detect glomerular mesangial cell proliferation. Real-time PCR, Western blot analysis, and ELISA evaluated the anti-inflammatory mechanism of TAT-CLs-DHA/siRNA.Results: We constructed the TAT-CLs-DHA/siRNA delivery system measuring approximately 140 nm with superior storage and serum stabilities. In vitro, it showed significantly greater uptake compared with unmodified liposomes and significant inhibition of glomerular mesangial cell proliferation. TAT-CLs-DHA/siRNA inhibited NF-κB activation in a concentration-dependent manner. Real-time PCR and Western blot analysis showed that TAT-CLs-DHA/siRNA downregulated expression of HMGB1 mRNA and protein. TAT-CLs-DHA/siRNA markedly diminished Toll-like receptor 4 (TLR4) expression and subsequent activation of MyD88, IRAK4, and NF-κB.Conclusion: TAT-CLs-DHA/siRNA may have the potential for treatment of inflammatory diseases such as LN mediated by the TLR4 signaling pathway.Keywords: cationic liposome, HMGB1 siRNA, DHA, Toll-like receptor 4
format	article
author	Diao L Tao J Wang Y Hu Y He W
author_facet	Diao L Tao J Wang Y Hu Y He W
author_sort	Diao L
title	Co-Delivery Of Dihydroartemisinin And HMGB1 siRNA By TAT-Modified Cationic Liposomes Through The TLR4 Signaling Pathway For Treatment Of Lupus Nephritis
title_short	Co-Delivery Of Dihydroartemisinin And HMGB1 siRNA By TAT-Modified Cationic Liposomes Through The TLR4 Signaling Pathway For Treatment Of Lupus Nephritis
title_full	Co-Delivery Of Dihydroartemisinin And HMGB1 siRNA By TAT-Modified Cationic Liposomes Through The TLR4 Signaling Pathway For Treatment Of Lupus Nephritis
title_fullStr	Co-Delivery Of Dihydroartemisinin And HMGB1 siRNA By TAT-Modified Cationic Liposomes Through The TLR4 Signaling Pathway For Treatment Of Lupus Nephritis
title_full_unstemmed	Co-Delivery Of Dihydroartemisinin And HMGB1 siRNA By TAT-Modified Cationic Liposomes Through The TLR4 Signaling Pathway For Treatment Of Lupus Nephritis
title_sort	co-delivery of dihydroartemisinin and hmgb1 sirna by tat-modified cationic liposomes through the tlr4 signaling pathway for treatment of lupus nephritis
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/5e921dc9440d484487aac485f1e287f4
work_keys_str_mv	AT diaol codeliveryofdihydroartemisininandhmgb1sirnabytatmodifiedcationicliposomesthroughthetlr4signalingpathwayfortreatmentoflupusnephritis AT taoj codeliveryofdihydroartemisininandhmgb1sirnabytatmodifiedcationicliposomesthroughthetlr4signalingpathwayfortreatmentoflupusnephritis AT wangy codeliveryofdihydroartemisininandhmgb1sirnabytatmodifiedcationicliposomesthroughthetlr4signalingpathwayfortreatmentoflupusnephritis AT huy codeliveryofdihydroartemisininandhmgb1sirnabytatmodifiedcationicliposomesthroughthetlr4signalingpathwayfortreatmentoflupusnephritis AT hew codeliveryofdihydroartemisininandhmgb1sirnabytatmodifiedcationicliposomesthroughthetlr4signalingpathwayfortreatmentoflupusnephritis
_version_	1718398123143856128

Co-Delivery Of Dihydroartemisinin And HMGB1 siRNA By TAT-Modified Cationic Liposomes Through The TLR4 Signaling Pathway For Treatment Of Lupus Nephritis

Ejemplares similares