Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNA

To solve the problem of transfection efficiency vs. cytotoxicity and tumor-targeting ability when polyethylenimine (PEI) was used as a nonviral gene delivery vector, new degradable PEI polymers were synthesized via cross-linking low-molecular-weight PEI with Pluronic P123 and then further coupled wi...

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Autors principals: Jing Hu, Wenfang Zhao, Kehai Liu, Qian Yu, Yuan Mao, Zeyu Lu, Yaguang Zhang, Manman Zhu
Format: Article
Idioma:English
Publicat: MDPI AG 2016-05-01
Col·lecció:Molecules
Matèries:
Accés en línia:http://www.mdpi.com/1420-3049/21/5/655
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author Jing Hu
Wenfang Zhao
Kehai Liu
Qian Yu
Yuan Mao
Zeyu Lu
Yaguang Zhang
Manman Zhu
author_facet Jing Hu
Wenfang Zhao
Kehai Liu
Qian Yu
Yuan Mao
Zeyu Lu
Yaguang Zhang
Manman Zhu
author_sort Jing Hu
collection DOAJ
description To solve the problem of transfection efficiency vs. cytotoxicity and tumor-targeting ability when polyethylenimine (PEI) was used as a nonviral gene delivery vector, new degradable PEI polymers were synthesized via cross-linking low-molecular-weight PEI with Pluronic P123 and then further coupled with a targeting peptide R4 (RGD) and a bifunctional R11 (RGD-NLS), which were termed as P123-PEI-R4 and P123-PEI-R11, respectively. Agarose gel electrophoresis showed that both P123-PEI-R4 and P123-PEI-R11 efficaciously condense plasmid DNA at a polymer-to-pDNA w/w ratio of 3.0 and 0.4, respectively. The polyplexes were stable in the presence of serum and could protect plasmid DNA against DNaseI. They had uniform spherical nanoparticles with appropriate sizes around 100–280 nm and zeta-potentials about +40 mV. Furthermore, in vitro experiments showed that these polyplexes had lower cytotoxicity at any concentration compared with PEI 25 kDa, thus giving promise to high transfection efficiency as compared with another P123-PEI derivate conjugated with trifunctional peptide RGD-TAT-NLS (P123-PEI-R18). More importantly, compared with the other polymers, P123-PEI-R11 showed the highest transfection efficiency with relatively lower cytotoxicity at any concentration, indicating that the new synthetic polymer P123-PEI-R11 could be used as a safe and efficient gene deliver vector.
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spelling doaj.art-ca9f2d2719d94dcea2d2dfab23f11a552022-12-22T03:55:48ZengMDPI AGMolecules1420-30492016-05-0121565510.3390/molecules21050655molecules21050655Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNAJing Hu0Wenfang Zhao1Kehai Liu2Qian Yu3Yuan Mao4Zeyu Lu5Yaguang Zhang6Manman Zhu7Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, ChinaDepartment of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, ChinaDepartment of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, ChinaDepartment of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, ChinaDepartment of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, ChinaDepartment of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, ChinaDepartment of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, ChinaDepartment of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, ChinaTo solve the problem of transfection efficiency vs. cytotoxicity and tumor-targeting ability when polyethylenimine (PEI) was used as a nonviral gene delivery vector, new degradable PEI polymers were synthesized via cross-linking low-molecular-weight PEI with Pluronic P123 and then further coupled with a targeting peptide R4 (RGD) and a bifunctional R11 (RGD-NLS), which were termed as P123-PEI-R4 and P123-PEI-R11, respectively. Agarose gel electrophoresis showed that both P123-PEI-R4 and P123-PEI-R11 efficaciously condense plasmid DNA at a polymer-to-pDNA w/w ratio of 3.0 and 0.4, respectively. The polyplexes were stable in the presence of serum and could protect plasmid DNA against DNaseI. They had uniform spherical nanoparticles with appropriate sizes around 100–280 nm and zeta-potentials about +40 mV. Furthermore, in vitro experiments showed that these polyplexes had lower cytotoxicity at any concentration compared with PEI 25 kDa, thus giving promise to high transfection efficiency as compared with another P123-PEI derivate conjugated with trifunctional peptide RGD-TAT-NLS (P123-PEI-R18). More importantly, compared with the other polymers, P123-PEI-R11 showed the highest transfection efficiency with relatively lower cytotoxicity at any concentration, indicating that the new synthetic polymer P123-PEI-R11 could be used as a safe and efficient gene deliver vector.http://www.mdpi.com/1420-3049/21/5/655polycationsRGDnuclear localization signalphysico-chemical propertiestransfection efficiency
spellingShingle Jing Hu
Wenfang Zhao
Kehai Liu
Qian Yu
Yuan Mao
Zeyu Lu
Yaguang Zhang
Manman Zhu
Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNA
Molecules
polycations
RGD
nuclear localization signal
physico-chemical properties
transfection efficiency
title Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNA
title_full Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNA
title_fullStr Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNA
title_full_unstemmed Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNA
title_short Low-Molecular Weight Polyethylenimine Modified with Pluronic 123 and RGD- or Chimeric RGD-NLS Peptide: Characteristics and Transfection Efficacy of Their Complexes with Plasmid DNA
title_sort low molecular weight polyethylenimine modified with pluronic 123 and rgd or chimeric rgd nls peptide characteristics and transfection efficacy of their complexes with plasmid dna
topic polycations
RGD
nuclear localization signal
physico-chemical properties
transfection efficiency
url http://www.mdpi.com/1420-3049/21/5/655
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