Liposomal codelivery of an SN38 prodrug and a survivin siRNA for tumor therapy

Ye Bi,1 Robert J Lee,1,2 Xinyu Wang,1 Yating Sun,1 Mengqiao Wang,1 Lianlian Li,1 Chenliang Li,1 Jing Xie,1 Lesheng Teng1 1School of Life Sciences, Jilin University, Changchun, Jilin, People’s Republic of China; 2Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Co...

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Autores principales:	Bi Y, Lee RJ, Wang X, Sun Y, Wang M, Li L, Li C, Xie J, Teng L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	SN38 survivin siRNA transferrin prodrug Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8db0d6001d8744e98dbbf27ac3c0593f
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spelling	oai:doaj.org-article:8db0d6001d8744e98dbbf27ac3c0593f2021-12-02T08:33:56ZLiposomal codelivery of an SN38 prodrug and a survivin siRNA for tumor therapy1178-2013https://doaj.org/article/8db0d6001d8744e98dbbf27ac3c0593f2018-10-01T00:00:00Zhttps://www.dovepress.com/liposomal-codelivery-of-an-sn38-prodrug-and-a-survivin-sirna-for-tumor-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ye Bi,1 Robert J Lee,1,2 Xinyu Wang,1 Yating Sun,1 Mengqiao Wang,1 Lianlian Li,1 Chenliang Li,1 Jing Xie,1 Lesheng Teng1 1School of Life Sciences, Jilin University, Changchun, Jilin, People’s Republic of China; 2Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA Purpose: A liposome-based siRNA–drug combination was evaluated as a potential therapeutic strategy to improve the curative effect. Methods: A topoisomerase inhibitor SN38 prodrug was combined with a survivin siRNA through codelivery using transferrin (Tf)-L-SN38/P/siRNA. In this combination, SN38 was conjugated to the cell penetrating peptide TAT through a polyethylene glycol (PEG) linker to synthesize TAT-PEG-SN38. The amphiphilic TAT-PEG-SN38 was used as an ingredient of liposomes to improve the cellular uptake. Protamine was added to form an electrostatic complex with siRNA in the core of the liposomes. Tf was introduced to enable tumor cell targeting of liposomes (Tf-L-SN38/P/siRNA). Results: Tf-L-SN38/P/siRNA exhibited a particle size of 148 nm and a ζ-potential of +7.8 mV. The cellular uptake and antitumor activity were dependent on Tf receptor targeting, TAT-PEG-SN38, and siRNA codelivery. Tf-L-SN38/P/siRNA was shown to be considerably more effective than liposomes carrying individual components. This combination induced potent tumor inhibition (76.8%) in HeLa cell xenograft tumor-bearing nude mice. Conclusion: These data indicated that Tf-L-SN38/P/siRNA was an effective system for codelivery of SN38 and a survivin siRNA and that its therapeutic potential deserved further evaluation. Keywords: SN38, survivin, siRNA, transferrin, prodrugBi YLee RJWang XSun YWang MLi LLi CXie JTeng LDove Medical PressarticleSN38survivinsiRNAtransferrinprodrugMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 5811-5822 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	SN38 survivin siRNA transferrin prodrug Medicine (General) R5-920
spellingShingle	SN38 survivin siRNA transferrin prodrug Medicine (General) R5-920 Bi Y Lee RJ Wang X Sun Y Wang M Li L Li C Xie J Teng L Liposomal codelivery of an SN38 prodrug and a survivin siRNA for tumor therapy
description	Ye Bi,1 Robert J Lee,1,2 Xinyu Wang,1 Yating Sun,1 Mengqiao Wang,1 Lianlian Li,1 Chenliang Li,1 Jing Xie,1 Lesheng Teng1 1School of Life Sciences, Jilin University, Changchun, Jilin, People’s Republic of China; 2Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA Purpose: A liposome-based siRNA–drug combination was evaluated as a potential therapeutic strategy to improve the curative effect. Methods: A topoisomerase inhibitor SN38 prodrug was combined with a survivin siRNA through codelivery using transferrin (Tf)-L-SN38/P/siRNA. In this combination, SN38 was conjugated to the cell penetrating peptide TAT through a polyethylene glycol (PEG) linker to synthesize TAT-PEG-SN38. The amphiphilic TAT-PEG-SN38 was used as an ingredient of liposomes to improve the cellular uptake. Protamine was added to form an electrostatic complex with siRNA in the core of the liposomes. Tf was introduced to enable tumor cell targeting of liposomes (Tf-L-SN38/P/siRNA). Results: Tf-L-SN38/P/siRNA exhibited a particle size of 148 nm and a ζ-potential of +7.8 mV. The cellular uptake and antitumor activity were dependent on Tf receptor targeting, TAT-PEG-SN38, and siRNA codelivery. Tf-L-SN38/P/siRNA was shown to be considerably more effective than liposomes carrying individual components. This combination induced potent tumor inhibition (76.8%) in HeLa cell xenograft tumor-bearing nude mice. Conclusion: These data indicated that Tf-L-SN38/P/siRNA was an effective system for codelivery of SN38 and a survivin siRNA and that its therapeutic potential deserved further evaluation. Keywords: SN38, survivin, siRNA, transferrin, prodrug
format	article
author	Bi Y Lee RJ Wang X Sun Y Wang M Li L Li C Xie J Teng L
author_facet	Bi Y Lee RJ Wang X Sun Y Wang M Li L Li C Xie J Teng L
author_sort	Bi Y
title	Liposomal codelivery of an SN38 prodrug and a survivin siRNA for tumor therapy
title_short	Liposomal codelivery of an SN38 prodrug and a survivin siRNA for tumor therapy
title_full	Liposomal codelivery of an SN38 prodrug and a survivin siRNA for tumor therapy
title_fullStr	Liposomal codelivery of an SN38 prodrug and a survivin siRNA for tumor therapy
title_full_unstemmed	Liposomal codelivery of an SN38 prodrug and a survivin siRNA for tumor therapy
title_sort	liposomal codelivery of an sn38 prodrug and a survivin sirna for tumor therapy
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/8db0d6001d8744e98dbbf27ac3c0593f
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_version_	1718398499153772544

Liposomal codelivery of an SN38 prodrug and a survivin siRNA for tumor therapy

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