Degradable polyethylenimine derivate coupled to a bifunctional peptide R13 as a new gene-delivery vector

Degradable polyethylenimine derivate coupled to a bifunctional peptide R13 as a new gene-delivery vector

Kehai Liu1,2,*, Xiaoyu Wang1,*, Wei Fan1, Qing Zhu2, Jingya Yang2, Jing Gao3, Shen Gao1 1Department of Pharmaceutics, Shanghai Hospital, Second Military Medical University, 2Department of Biopharmaceutics, School of Food Science and Technology, Shanghai Ocean University, 3Department of Pharmaceutics...

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Autores principales: Liu K, Wang X, Fan W, Zhu Q, Yang J, Gao J, Gao S
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2012
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/9cf92e1791e54fe5acea967e149067a7
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spelling oai:doaj.org-article:9cf92e1791e54fe5acea967e149067a72021-12-02T04:46:21ZDegradable polyethylenimine derivate coupled to a bifunctional peptide R13 as a new gene-delivery vector1176-91141178-2013https://doaj.org/article/9cf92e1791e54fe5acea967e149067a72012-02-01T00:00:00Zhttp://www.dovepress.com/degradable-polyethylenimine-derivate-coupled-to-a-bifunctional-peptide-a9382https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Kehai Liu1,2,*, Xiaoyu Wang1,*, Wei Fan1, Qing Zhu2, Jingya Yang2, Jing Gao3, Shen Gao1 1Department of Pharmaceutics, Shanghai Hospital, Second Military Medical University, 2Department of Biopharmaceutics, School of Food Science and Technology, Shanghai Ocean University, 3Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China*The first two authors contributed equally to this workBackground: To solve the efficiency versus cytotoxicity and tumor-targeting problems of polyethylenimine (PEI) used as a nonviral gene delivery vector, a degradable PEI derivate coupled to a bifunctional peptide R13 was developed.Methods: First, we synthesized a degradable PEI derivate by crosslinking low-molecular-weight PEI with pluronic P123, then used tumor-targeting peptide arginine-glycine-aspartate-cysteine (RGDC), in conjunction with the cell-penetrating peptide Tat (49–57), to yield a bifunctional peptide RGDC-Tat (49–57) named R13, which can improve cell selection and increase cellular uptake, and, lastly, adopted R13 to modify the PEI derivates so as to prepare a new polymeric gene vector (P123-PEI-R13). The new gene vector was characterized in terms of its chemical structure and biophysical parameters. We also investigated the specificity, cytotoxicity, and gene transfection efficiency of this vector in avß3-positive human cervical carcinoma Hela cells and murine melanoma B16 cells in vitro.Results: The vector showed controlled degradation, strong targeting specificity to avß3 receptor, and noncytotoxicity in Hela cells and B16 cells at higher doses, in contrast to PEI 25 KDa. The particle size of P123-PEI-R13/DNA complexes was around 100–250 nm, with proper zeta potential. The nanoparticles can protect plasmid DNA from being digested by DNase I at a concentration of 6 U DNase I/µg DNA. The nanoparticles were resistant to dissociation induced by 50% fetal bovine serum and 600 µg/mL sodium heparin. P123-PEI-R13 also revealed higher transfection efficiency in two cell lines as compared with PEI 25 KDa.Conclusion: P123-PEI-R13 is a potential candidate as a safe and efficient gene-delivery carrier for gene therapy.Keywords: nonviral gene vector, polyethylenimine, P123, αvß3, cell-penetrating peptidesLiu KWang XFan WZhu QYang JGao JGao SDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 1149-1162 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Liu K
Wang X
Fan W
Zhu Q
Yang J
Gao J
Gao S
Degradable polyethylenimine derivate coupled to a bifunctional peptide R13 as a new gene-delivery vector
description Kehai Liu1,2,*, Xiaoyu Wang1,*, Wei Fan1, Qing Zhu2, Jingya Yang2, Jing Gao3, Shen Gao1 1Department of Pharmaceutics, Shanghai Hospital, Second Military Medical University, 2Department of Biopharmaceutics, School of Food Science and Technology, Shanghai Ocean University, 3Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China*The first two authors contributed equally to this workBackground: To solve the efficiency versus cytotoxicity and tumor-targeting problems of polyethylenimine (PEI) used as a nonviral gene delivery vector, a degradable PEI derivate coupled to a bifunctional peptide R13 was developed.Methods: First, we synthesized a degradable PEI derivate by crosslinking low-molecular-weight PEI with pluronic P123, then used tumor-targeting peptide arginine-glycine-aspartate-cysteine (RGDC), in conjunction with the cell-penetrating peptide Tat (49–57), to yield a bifunctional peptide RGDC-Tat (49–57) named R13, which can improve cell selection and increase cellular uptake, and, lastly, adopted R13 to modify the PEI derivates so as to prepare a new polymeric gene vector (P123-PEI-R13). The new gene vector was characterized in terms of its chemical structure and biophysical parameters. We also investigated the specificity, cytotoxicity, and gene transfection efficiency of this vector in avß3-positive human cervical carcinoma Hela cells and murine melanoma B16 cells in vitro.Results: The vector showed controlled degradation, strong targeting specificity to avß3 receptor, and noncytotoxicity in Hela cells and B16 cells at higher doses, in contrast to PEI 25 KDa. The particle size of P123-PEI-R13/DNA complexes was around 100–250 nm, with proper zeta potential. The nanoparticles can protect plasmid DNA from being digested by DNase I at a concentration of 6 U DNase I/µg DNA. The nanoparticles were resistant to dissociation induced by 50% fetal bovine serum and 600 µg/mL sodium heparin. P123-PEI-R13 also revealed higher transfection efficiency in two cell lines as compared with PEI 25 KDa.Conclusion: P123-PEI-R13 is a potential candidate as a safe and efficient gene-delivery carrier for gene therapy.Keywords: nonviral gene vector, polyethylenimine, P123, αvß3, cell-penetrating peptides
format article
author Liu K
Wang X
Fan W
Zhu Q
Yang J
Gao J
Gao S
author_facet Liu K
Wang X
Fan W
Zhu Q
Yang J
Gao J
Gao S
author_sort Liu K
title Degradable polyethylenimine derivate coupled to a bifunctional peptide R13 as a new gene-delivery vector
title_short Degradable polyethylenimine derivate coupled to a bifunctional peptide R13 as a new gene-delivery vector
title_full Degradable polyethylenimine derivate coupled to a bifunctional peptide R13 as a new gene-delivery vector
title_fullStr Degradable polyethylenimine derivate coupled to a bifunctional peptide R13 as a new gene-delivery vector
title_full_unstemmed Degradable polyethylenimine derivate coupled to a bifunctional peptide R13 as a new gene-delivery vector
title_sort degradable polyethylenimine derivate coupled to a bifunctional peptide r13 as a new gene-delivery vector
publisher Dove Medical Press
publishDate 2012
url https://doaj.org/article/9cf92e1791e54fe5acea967e149067a7
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AT zhuq degradablepolyethyleniminederivatecoupledtoabifunctionalpeptider13asanewgenedeliveryvector
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