Synthetic polyspermine imidazole-4, 5-amide as an efficient and cytotoxicity-free gene delivery system

Shi-Yue Duan, Xue-Mei Ge, Nan Lu, Fei Wu, Weien Yuan, Tuo JinSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, People&#39;s Republic of ChinaAbstract: A chemically dynamic spermine-based polymer: polyspermine imidazole-4, 5-amide (PSIA, Mw &gt; 7 kDa) was designed,...

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Autores principales:	Duan S, Ge X, Lu N, Wu F, Yuan W, Jin T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/14780350d32545e0abb6288c7ee200b6
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spelling	oai:doaj.org-article:14780350d32545e0abb6288c7ee200b62021-12-02T06:34:20ZSynthetic polyspermine imidazole-4, 5-amide as an efficient and cytotoxicity-free gene delivery system1176-91141178-2013https://doaj.org/article/14780350d32545e0abb6288c7ee200b62012-07-01T00:00:00Zhttp://www.dovepress.com/synthetic-polyspermine-imidazole-4-5-amide-as-an-efficient-and-cytotox-a10447https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Shi-Yue Duan, Xue-Mei Ge, Nan Lu, Fei Wu, Weien Yuan, Tuo JinSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, People&#39;s Republic of ChinaAbstract: A chemically dynamic spermine-based polymer: polyspermine imidazole-4, 5-amide (PSIA, Mw &gt; 7 kDa) was designed, synthesized, and evaluated in terms of its ability to deliver nucleic acids. This polymer was made from an endogenous monomer professionally condensing genes in sperms, spermine, and a known safety drug metabolite, imidazole-4, 5-dicarboxylic acid, through a bis-amide bond conjugated with the imidazole ring. This polymer can condense pDNA at a W/W ratio above 10 to form polyplexes (100&ndash;200 nm in diameter), which is consistent with the observation by transmission electron microscopy (TEM), and the zeta potential was in the range of 10&ndash;20 mV. The pDNA packaged polymer was stable in phosphate buffer solution (PBS) at pH 7.4 (simulated body fluid) while the polyplexes were releasing pDNA into the solution at pH 5.8 (simulated endo-lysosomes) due to the degradation of the bis-amide linkages in response to changes in pH values. PSIA-polyplexes were able to achieve efficient cellular uptake and luciferase gene silencing by co-transfection of pDNA and siRNA in COS-7 cells and HepG2 cells with negligible cytotoxicity. Biodistribution of Rhodamine B-labeled PSIA-polyplexes after being systemically injected in BALB/c nude-mice showed that the polyplexes circulated throughout the body, accumulated mainly in the kidney at 4 hours of sample administration, and moved to the liver and spleen after 24 hours. All the results suggested that PSIA offered a promising example to balance the transfection efficiency and toxicity of a synthetic carrier system for the delivery of therapeutic nucleic acids.Keywords: gene delivery, polyspermine, cytotoxicity, transfection efficiency, biodistributionDuan SGe XLu NWu FYuan WJin TDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 3813-3822 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Duan S Ge X Lu N Wu F Yuan W Jin T Synthetic polyspermine imidazole-4, 5-amide as an efficient and cytotoxicity-free gene delivery system
description	Shi-Yue Duan, Xue-Mei Ge, Nan Lu, Fei Wu, Weien Yuan, Tuo JinSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, People&#39;s Republic of ChinaAbstract: A chemically dynamic spermine-based polymer: polyspermine imidazole-4, 5-amide (PSIA, Mw &gt; 7 kDa) was designed, synthesized, and evaluated in terms of its ability to deliver nucleic acids. This polymer was made from an endogenous monomer professionally condensing genes in sperms, spermine, and a known safety drug metabolite, imidazole-4, 5-dicarboxylic acid, through a bis-amide bond conjugated with the imidazole ring. This polymer can condense pDNA at a W/W ratio above 10 to form polyplexes (100&ndash;200 nm in diameter), which is consistent with the observation by transmission electron microscopy (TEM), and the zeta potential was in the range of 10&ndash;20 mV. The pDNA packaged polymer was stable in phosphate buffer solution (PBS) at pH 7.4 (simulated body fluid) while the polyplexes were releasing pDNA into the solution at pH 5.8 (simulated endo-lysosomes) due to the degradation of the bis-amide linkages in response to changes in pH values. PSIA-polyplexes were able to achieve efficient cellular uptake and luciferase gene silencing by co-transfection of pDNA and siRNA in COS-7 cells and HepG2 cells with negligible cytotoxicity. Biodistribution of Rhodamine B-labeled PSIA-polyplexes after being systemically injected in BALB/c nude-mice showed that the polyplexes circulated throughout the body, accumulated mainly in the kidney at 4 hours of sample administration, and moved to the liver and spleen after 24 hours. All the results suggested that PSIA offered a promising example to balance the transfection efficiency and toxicity of a synthetic carrier system for the delivery of therapeutic nucleic acids.Keywords: gene delivery, polyspermine, cytotoxicity, transfection efficiency, biodistribution
format	article
author	Duan S Ge X Lu N Wu F Yuan W Jin T
author_facet	Duan S Ge X Lu N Wu F Yuan W Jin T
author_sort	Duan S
title	Synthetic polyspermine imidazole-4, 5-amide as an efficient and cytotoxicity-free gene delivery system
title_short	Synthetic polyspermine imidazole-4, 5-amide as an efficient and cytotoxicity-free gene delivery system
title_full	Synthetic polyspermine imidazole-4, 5-amide as an efficient and cytotoxicity-free gene delivery system
title_fullStr	Synthetic polyspermine imidazole-4, 5-amide as an efficient and cytotoxicity-free gene delivery system
title_full_unstemmed	Synthetic polyspermine imidazole-4, 5-amide as an efficient and cytotoxicity-free gene delivery system
title_sort	synthetic polyspermine imidazole-4, 5-amide as an efficient and cytotoxicity-free gene delivery system
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/14780350d32545e0abb6288c7ee200b6
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Synthetic polyspermine imidazole-4, 5-amide as an efficient and cytotoxicity-free gene delivery system

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