Dual-degradable disulfide-containing PEI–Pluronic/DNA polyplexes: transfection efficiency and balancing protection and DNA release

Dual-degradable disulfide-containing PEI–Pluronic/DNA polyplexes: transfection efficiency and balancing protection and DNA release

Lifen Zhang,* Zhenzhen Chen,* Yanfeng LiState Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Institute of Biochemical Engineering and Environmental Technology, Lanz...

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Autores principales: Zhang L, Chen Z, Li Y
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2013
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/f24964e5a397412abe47397b9c104e8f
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spelling oai:doaj.org-article:f24964e5a397412abe47397b9c104e8f2021-12-02T08:06:26ZDual-degradable disulfide-containing PEI–Pluronic/DNA polyplexes: transfection efficiency and balancing protection and DNA release1176-91141178-2013https://doaj.org/article/f24964e5a397412abe47397b9c104e8f2013-09-01T00:00:00Zhttp://www.dovepress.com/dual-degradable-disulfide-containing-peindashpluronicdna-polyplexes-tr-a14519https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Lifen Zhang,* Zhenzhen Chen,* Yanfeng LiState Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Institute of Biochemical Engineering and Environmental Technology, Lanzhou University, Lanzhou, People's Republic of China*These authors contributed equally to this workAbstract: Polymeric gene-delivery vectors to achieve lack of toxicity and a balance between protection and DNA release remains a formidable challenge. Incorporating intracellular environment-responsive degradable bonds is an appreciable step toward developing safer transfection agents. In this study, novel, dual-degradable polycation copolymers (Pluronic-diacrylate [PA]–polyethyleneimine [PEI]–SS) were synthesized through the addition of low molecular weight (800 Da) PEI cross-linked with SS (PEI-SS) to PA. Three PA-PEI-SS copolymers (PA-PEI-SS1, 2, and 3) with different PEI-SS to Pluronic molar ratios were investigated and found to strongly condense plasmid DNA into positively charged nanoparticles with an average particle size of approximately 200 nm and to possess higher stability against DNase I digestion and sodium heparin. Disulfide and ester bonds of the copolymers were susceptible to intracellular redox conditions. In vitro experiments demonstrated that the PA-PEI-SS copolymers had significantly lower cytotoxicity and higher transfection efficiency in both BGC-823 and 293T cell lines than the controls of degradable PEI-SS and nondegradable 25 kDa PEI. Transfection activity was influenced by the PEI-SS content in the polymers and PA-PEI-SS1 showed the highest efficiency of the three copolymers. These studies suggest that these dual-degradable copolymers could be used as potential biocompatible gene delivery carriers.Keywords: Pluronic, PEI, gene vector, dual-degradable, disulfide-containing linkerZhang LChen ZLi YDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss Issue 1, Pp 3689-3701 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Zhang L
Chen Z
Li Y
Dual-degradable disulfide-containing PEI–Pluronic/DNA polyplexes: transfection efficiency and balancing protection and DNA release
description Lifen Zhang,* Zhenzhen Chen,* Yanfeng LiState Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Institute of Biochemical Engineering and Environmental Technology, Lanzhou University, Lanzhou, People's Republic of China*These authors contributed equally to this workAbstract: Polymeric gene-delivery vectors to achieve lack of toxicity and a balance between protection and DNA release remains a formidable challenge. Incorporating intracellular environment-responsive degradable bonds is an appreciable step toward developing safer transfection agents. In this study, novel, dual-degradable polycation copolymers (Pluronic-diacrylate [PA]–polyethyleneimine [PEI]–SS) were synthesized through the addition of low molecular weight (800 Da) PEI cross-linked with SS (PEI-SS) to PA. Three PA-PEI-SS copolymers (PA-PEI-SS1, 2, and 3) with different PEI-SS to Pluronic molar ratios were investigated and found to strongly condense plasmid DNA into positively charged nanoparticles with an average particle size of approximately 200 nm and to possess higher stability against DNase I digestion and sodium heparin. Disulfide and ester bonds of the copolymers were susceptible to intracellular redox conditions. In vitro experiments demonstrated that the PA-PEI-SS copolymers had significantly lower cytotoxicity and higher transfection efficiency in both BGC-823 and 293T cell lines than the controls of degradable PEI-SS and nondegradable 25 kDa PEI. Transfection activity was influenced by the PEI-SS content in the polymers and PA-PEI-SS1 showed the highest efficiency of the three copolymers. These studies suggest that these dual-degradable copolymers could be used as potential biocompatible gene delivery carriers.Keywords: Pluronic, PEI, gene vector, dual-degradable, disulfide-containing linker
format article
author Zhang L
Chen Z
Li Y
author_facet Zhang L
Chen Z
Li Y
author_sort Zhang L
title Dual-degradable disulfide-containing PEI–Pluronic/DNA polyplexes: transfection efficiency and balancing protection and DNA release
title_short Dual-degradable disulfide-containing PEI–Pluronic/DNA polyplexes: transfection efficiency and balancing protection and DNA release
title_full Dual-degradable disulfide-containing PEI–Pluronic/DNA polyplexes: transfection efficiency and balancing protection and DNA release
title_fullStr Dual-degradable disulfide-containing PEI–Pluronic/DNA polyplexes: transfection efficiency and balancing protection and DNA release
title_full_unstemmed Dual-degradable disulfide-containing PEI–Pluronic/DNA polyplexes: transfection efficiency and balancing protection and DNA release
title_sort dual-degradable disulfide-containing pei–pluronic/dna polyplexes: transfection efficiency and balancing protection and dna release
publisher Dove Medical Press
publishDate 2013
url https://doaj.org/article/f24964e5a397412abe47397b9c104e8f
work_keys_str_mv AT zhangl dualdegradabledisulfidecontainingpeindashpluronicdnapolyplexestransfectionefficiencyandbalancingprotectionanddnarelease
AT chenz dualdegradabledisulfidecontainingpeindashpluronicdnapolyplexestransfectionefficiencyandbalancingprotectionanddnarelease
AT liy dualdegradabledisulfidecontainingpeindashpluronicdnapolyplexestransfectionefficiencyandbalancingprotectionanddnarelease
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