Novel RGD-lipid conjugate-modified liposomes for enhancing siRNA delivery in human retinal pigment epithelial cells

Cheng-Wei Chen1, Da-Wen Lu2, Ming-Kung Yeh3, Chia-Yang Shiau4, Chiao-Hsi Chiang1,5 1Graduate Institute of Life Sciences, 2Department of Ophthalmology, Tri-Service General Hospital, 3Institution of Preventive Medicine, 4Graduate Institute of Medical Sciences, 5School of Pharmacy, National Defense Med...

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Autores principales:	Chen CW, Lu DW, Yeh MK, Shiau CY, Chiang CH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5cfc1c56b60f49f88115b1e65a853ed3
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spelling	oai:doaj.org-article:5cfc1c56b60f49f88115b1e65a853ed32021-12-02T02:16:45ZNovel RGD-lipid conjugate-modified liposomes for enhancing siRNA delivery in human retinal pigment epithelial cells1176-91141178-2013https://doaj.org/article/5cfc1c56b60f49f88115b1e65a853ed32011-10-01T00:00:00Zhttp://www.dovepress.com/novel-rgd-lipid-conjugate-modified-liposomes-for-enhancing-sirna-deliv-a8546https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Cheng-Wei Chen1, Da-Wen Lu2, Ming-Kung Yeh3, Chia-Yang Shiau4, Chiao-Hsi Chiang1,5 1Graduate Institute of Life Sciences, 2Department of Ophthalmology, Tri-Service General Hospital, 3Institution of Preventive Medicine, 4Graduate Institute of Medical Sciences, 5School of Pharmacy, National Defense Medical Center, Neihu, Taipei, Taiwan Background: Human retinal pigment epithelial cells are promising target sites for small interfering RNA (siRNA) that might be used for the prevention and/or treatment of choroidal neovascularization by inhibiting the expression of angiogenic factor; for example, by downregulating expression of the vascular endothelial growth factor gene. Methods: A novel functional lipid, DSPE-PEG-RGD, a Arg(R)-Gly(G)-Asp(D) motif peptide conjugated to 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine- N-[maleimide (polyethylene glycol)-2000], was synthesized for the preparation of siRNA-loaded RGD-PEGylated liposomes to enhance uptake of encapsulated siRNA in retinal pigment epithelial cells. Various liposomes, with 1 mol% and 5 mol% PEGylated lipid or 1 mol% and 5 mol% RGD-PEGylated lipid, were fabricated. Results: Characterization of the liposomes, including siRNA entrapment efficiency, average particle size and &zeta;-potential, were determined to be as follows: &gt;96%, 129.7 &plusmn; 51 to 230.7 &plusmn; 60.7 nm, and 17.3 &plusmn; 0.6 to 32 &plusmn; 1.3 mV, respectively. For the in vitro retinal pigment epithelial cell studies, the RGD-PEGylated liposomes had high delivery efficiency with siRNA delivery, about a four-fold increase compared with the PEGylated liposomes. Comparison of the various liposomes showed that the 1 mol% RGD-modified liposome had less cytotoxicity and higher siRNA delivery efficiency than the other liposomes. The antibody blocking assay confirmed that uptake of the 1 mol% RGD-PEGylated liposome was via integrin receptor-mediated endocytosis in retinal pigment epithelial cells. Conclusion: The results of this study suggest that RGD-PEGylated liposomes might be useful for siRNA delivery into retinal pigment epithelial cells by integrin receptor-medicated endocytosis. Keywords: Arg-Gly-Asp, RGD, small interfering RNA, liposome, retinal pigment epithelial cellsChen CWLu DWYeh MKShiau CYChiang CHDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 2567-2580 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Chen CW Lu DW Yeh MK Shiau CY Chiang CH Novel RGD-lipid conjugate-modified liposomes for enhancing siRNA delivery in human retinal pigment epithelial cells
description	Cheng-Wei Chen1, Da-Wen Lu2, Ming-Kung Yeh3, Chia-Yang Shiau4, Chiao-Hsi Chiang1,5 1Graduate Institute of Life Sciences, 2Department of Ophthalmology, Tri-Service General Hospital, 3Institution of Preventive Medicine, 4Graduate Institute of Medical Sciences, 5School of Pharmacy, National Defense Medical Center, Neihu, Taipei, Taiwan Background: Human retinal pigment epithelial cells are promising target sites for small interfering RNA (siRNA) that might be used for the prevention and/or treatment of choroidal neovascularization by inhibiting the expression of angiogenic factor; for example, by downregulating expression of the vascular endothelial growth factor gene. Methods: A novel functional lipid, DSPE-PEG-RGD, a Arg(R)-Gly(G)-Asp(D) motif peptide conjugated to 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine- N-[maleimide (polyethylene glycol)-2000], was synthesized for the preparation of siRNA-loaded RGD-PEGylated liposomes to enhance uptake of encapsulated siRNA in retinal pigment epithelial cells. Various liposomes, with 1 mol% and 5 mol% PEGylated lipid or 1 mol% and 5 mol% RGD-PEGylated lipid, were fabricated. Results: Characterization of the liposomes, including siRNA entrapment efficiency, average particle size and &zeta;-potential, were determined to be as follows: &gt;96%, 129.7 &plusmn; 51 to 230.7 &plusmn; 60.7 nm, and 17.3 &plusmn; 0.6 to 32 &plusmn; 1.3 mV, respectively. For the in vitro retinal pigment epithelial cell studies, the RGD-PEGylated liposomes had high delivery efficiency with siRNA delivery, about a four-fold increase compared with the PEGylated liposomes. Comparison of the various liposomes showed that the 1 mol% RGD-modified liposome had less cytotoxicity and higher siRNA delivery efficiency than the other liposomes. The antibody blocking assay confirmed that uptake of the 1 mol% RGD-PEGylated liposome was via integrin receptor-mediated endocytosis in retinal pigment epithelial cells. Conclusion: The results of this study suggest that RGD-PEGylated liposomes might be useful for siRNA delivery into retinal pigment epithelial cells by integrin receptor-medicated endocytosis. Keywords: Arg-Gly-Asp, RGD, small interfering RNA, liposome, retinal pigment epithelial cells
format	article
author	Chen CW Lu DW Yeh MK Shiau CY Chiang CH
author_facet	Chen CW Lu DW Yeh MK Shiau CY Chiang CH
author_sort	Chen CW
title	Novel RGD-lipid conjugate-modified liposomes for enhancing siRNA delivery in human retinal pigment epithelial cells
title_short	Novel RGD-lipid conjugate-modified liposomes for enhancing siRNA delivery in human retinal pigment epithelial cells
title_full	Novel RGD-lipid conjugate-modified liposomes for enhancing siRNA delivery in human retinal pigment epithelial cells
title_fullStr	Novel RGD-lipid conjugate-modified liposomes for enhancing siRNA delivery in human retinal pigment epithelial cells
title_full_unstemmed	Novel RGD-lipid conjugate-modified liposomes for enhancing siRNA delivery in human retinal pigment epithelial cells
title_sort	novel rgd-lipid conjugate-modified liposomes for enhancing sirna delivery in human retinal pigment epithelial cells
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/5cfc1c56b60f49f88115b1e65a853ed3
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Novel RGD-lipid conjugate-modified liposomes for enhancing siRNA delivery in human retinal pigment epithelial cells

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