Polyamidoamine (PAMAM) dendrimers modified with cathepsin-B cleavable oligopeptides for enhanced gene delivery

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Title
Polyamidoamine (PAMAM) dendrimers modified with cathepsin-B cleavable oligopeptides for enhanced gene delivery
Author(s)
Seulgi Lee; S J Son; S J Song; Tai Hwan Ha; J S Choi
Bibliographic Citation
Polymers, vol. 9, no. 6, pp. 224-224
Publication Year
2017
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.
Keyword
ArginineCathepsin BGene deliveryGFLG peptideHistidinePoly(amidoamine) dendrimerPolyplex
ISSN
2073-4360
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/polym9060224
Type
Article
Appears in Collections:
Division of Biomaterials Research > Bionanotechnology Research Center > 1. Journal Articles
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