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Polymers 2017, 9(6), 224; doi:10.3390/polym9060224

Polyamidoamine (PAMAM) Dendrimers Modified with Cathepsin-B Cleavable Oligopeptides for Enhanced Gene Delivery

1
Department of Biochemistry, Chungnam National University, Daejeon 305-764, Korea
2
Hazards Monitoring BNT Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon 34141, Korea
3
Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 34134, Korea
4
Department of Nanobiotechnology, KRIBB School of Biotechnology, Korea University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon 34113, Korea
*
Authors to whom correspondence should be addressed.
Academic Editor: Ravin Narain
Received: 15 March 2017 / Revised: 4 June 2017 / Accepted: 12 June 2017 / Published: 14 June 2017
(This article belongs to the Special Issue Polymers and Nanogels for Gene Therapy)
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Abstract

Because of the complex mechanisms mediating cancer onset, prognosis, and metastatic behavior, different therapeutic approaches targeting these mechanisms have been investigated. Recent advancements in nanocarrier-based drug and gene delivery methods have encouraged scientific groups to investigate various novel therapeutic techniques. In this study, a poly(amidoamine) (PAMAM) polymer-based gene carrier containing the cathepsin B-enzyme sensitive sequence (glycine-phenylalanine-leucine-glycine, GFLG) was evaluated to determine transfection efficiency. Following the GFLG sequence, the surface of PAMAM generation 4 (G4) was conjugated with histidine (H) and arginine (R) for improved endosomal escape and cellular uptake, respectively. The successful synthesis of G4-GLFG-H-R was confirmed by 1H-nuclear magnetic resonance spectroscopy. The polyplex composed of G4-GLFG-H-R and pDNA was simulated by the enzyme cathepsin B and induced endosomal escape of pDNA, which was confirmed by gel electrophoresis. Compared with the G4 control, enzyme-sensitive G4-GLFG-H-R showed higher transfection efficiency and lower cytotoxicity in HeLa cells. These results demonstrated that G4-GLFG-H-R may be a highly potent and efficient carrier for gene therapy applications. View Full-Text
Keywords: gene delivery; polyplex; poly(amidoamine) dendrimer; GFLG peptide; cathepsin B; histidine; arginine gene delivery; polyplex; poly(amidoamine) dendrimer; GFLG peptide; cathepsin B; histidine; arginine
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Lee, S.; Son, S.J.; Song, S.J.; Ha, T.H.; Choi, J.S. Polyamidoamine (PAMAM) Dendrimers Modified with Cathepsin-B Cleavable Oligopeptides for Enhanced Gene Delivery. Polymers 2017, 9, 224.

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