Coupling of a bifunctional peptide R13 to OTMCS-PEI copolymer as a gene vector increases transfection efficiency and tumor targeting

Hui Lv,1,* Qing Zhu,1,* Kewu Liu,2 Manman Zhu,1 Wenfang Zhao,1 Yuan Mao,1 Kehai Liu1 1Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, People's Republic of China; 2Heilongjiang Forest By-Product and Speciality Institute, Mudanjiang...

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Autores principales:	Lv H, Zhu Q, Liu K, Zhu M, Zhao W, Mao Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a9efe845c0b04ab1a99579cec4a9b17e
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spelling	oai:doaj.org-article:a9efe845c0b04ab1a99579cec4a9b17e2021-12-02T02:17:53ZCoupling of a bifunctional peptide R13 to OTMCS-PEI copolymer as a gene vector increases transfection efficiency and tumor targeting1178-2013https://doaj.org/article/a9efe845c0b04ab1a99579cec4a9b17e2014-03-01T00:00:00Zhttp://www.dovepress.com/coupling-of-a-bifunctional-peptide-r13-to-otmcs-pei-copolymer-as-a-gen-a16079https://doaj.org/toc/1178-2013 Hui Lv,1,* Qing Zhu,1,* Kewu Liu,2 Manman Zhu,1 Wenfang Zhao,1 Yuan Mao,1 Kehai Liu1 1Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, People's Republic of China; 2Heilongjiang Forest By-Product and Speciality Institute, Mudanjiang, People's Republic of China *These authors contributed equally to this work Background: A degradable polyethylenimine (PEI) derivative coupled to a bifunctional peptide R13 was developed to solve the transfection efficiency versus cytotoxicity and tumor-targeting problems of PEI when used as a gene vector. Methods: We crossed-linked low molecular weight PEI with N-octyl-N-quaternary chitosan (OTMCS) to synthesize a degradable PEI derivative (OTMCS-PEI), and then used a bifunctional peptide, RGDC-Tat (49–57) called R13 to modify OTMCS-PEI so as to prepare a new gene vector, OTMCS-PEI-R13. This new gene vector was characterized by various physicochemical methods. Its cytotoxicity and gene transfection efficiency were also determined both in vitro and in vivo. Results: The vector showed controlled degradation and excellent buffering capacity. The particle size of the OTMCS-PEI-R13/DNA complexes was around 150–250 nm and the zeta potential ranged from 10 mV to 30 mV. The polymer could protect plasmid DNA from being digested by DNase I at a concentration of 23.5 U DNase I/µg DNA. Further, the polymer was resistant to dissociation induced by 50% fetal bovine serum and 400 µg/mL sodium heparin. Compared with PEI 25 kDa, the OTMCS-PEI-R13/DNA complexes showed higher transfection efficiency both in vitro and in vivo. Further, compared with OTMCS-PEI, distribution of OTMCS-PEI-R13 at tumor sites was markedly enhanced, indicating the tumor-targeting specificity of R13. Conclusion: OTMCS-PEI-R13 could be a potential candidate as a safe and efficient gene delivery carrier for gene therapy. Keywords: nonviral gene vector, polyethylenimine, R13, transfection efficiency, tumor-targetingLv HZhu QLiu KZhu MZhao WMao YLiu KDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 1311-1322 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Lv H Zhu Q Liu K Zhu M Zhao W Mao Y Liu K Coupling of a bifunctional peptide R13 to OTMCS-PEI copolymer as a gene vector increases transfection efficiency and tumor targeting
description	Hui Lv,1,* Qing Zhu,1,* Kewu Liu,2 Manman Zhu,1 Wenfang Zhao,1 Yuan Mao,1 Kehai Liu1 1Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, People's Republic of China; 2Heilongjiang Forest By-Product and Speciality Institute, Mudanjiang, People's Republic of China *These authors contributed equally to this work Background: A degradable polyethylenimine (PEI) derivative coupled to a bifunctional peptide R13 was developed to solve the transfection efficiency versus cytotoxicity and tumor-targeting problems of PEI when used as a gene vector. Methods: We crossed-linked low molecular weight PEI with N-octyl-N-quaternary chitosan (OTMCS) to synthesize a degradable PEI derivative (OTMCS-PEI), and then used a bifunctional peptide, RGDC-Tat (49–57) called R13 to modify OTMCS-PEI so as to prepare a new gene vector, OTMCS-PEI-R13. This new gene vector was characterized by various physicochemical methods. Its cytotoxicity and gene transfection efficiency were also determined both in vitro and in vivo. Results: The vector showed controlled degradation and excellent buffering capacity. The particle size of the OTMCS-PEI-R13/DNA complexes was around 150–250 nm and the zeta potential ranged from 10 mV to 30 mV. The polymer could protect plasmid DNA from being digested by DNase I at a concentration of 23.5 U DNase I/µg DNA. Further, the polymer was resistant to dissociation induced by 50% fetal bovine serum and 400 µg/mL sodium heparin. Compared with PEI 25 kDa, the OTMCS-PEI-R13/DNA complexes showed higher transfection efficiency both in vitro and in vivo. Further, compared with OTMCS-PEI, distribution of OTMCS-PEI-R13 at tumor sites was markedly enhanced, indicating the tumor-targeting specificity of R13. Conclusion: OTMCS-PEI-R13 could be a potential candidate as a safe and efficient gene delivery carrier for gene therapy. Keywords: nonviral gene vector, polyethylenimine, R13, transfection efficiency, tumor-targeting
format	article
author	Lv H Zhu Q Liu K Zhu M Zhao W Mao Y Liu K
author_facet	Lv H Zhu Q Liu K Zhu M Zhao W Mao Y Liu K
author_sort	Lv H
title	Coupling of a bifunctional peptide R13 to OTMCS-PEI copolymer as a gene vector increases transfection efficiency and tumor targeting
title_short	Coupling of a bifunctional peptide R13 to OTMCS-PEI copolymer as a gene vector increases transfection efficiency and tumor targeting
title_full	Coupling of a bifunctional peptide R13 to OTMCS-PEI copolymer as a gene vector increases transfection efficiency and tumor targeting
title_fullStr	Coupling of a bifunctional peptide R13 to OTMCS-PEI copolymer as a gene vector increases transfection efficiency and tumor targeting
title_full_unstemmed	Coupling of a bifunctional peptide R13 to OTMCS-PEI copolymer as a gene vector increases transfection efficiency and tumor targeting
title_sort	coupling of a bifunctional peptide r13 to otmcs-pei copolymer as a gene vector increases transfection efficiency and tumor targeting
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/a9efe845c0b04ab1a99579cec4a9b17e
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Coupling of a bifunctional peptide R13 to OTMCS-PEI copolymer as a gene vector increases transfection efficiency and tumor targeting

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