Preparation and characterization of laminin-derived peptide AG73-coated liposomes as a selective gene delivery tool.

  • Negishi Y
  • Omata D
  • Iijima H
 et al. 
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Targeted gene delivery to cancer cells is considered as a promising strategy for cancer therapy. Since, several targeting ligands have been studied for cancer gene therapy, such as transferrin, folate, anisamide, RGD-peptide, and antibodies. We have focused on AG73 peptide, which is derived from the globular domain of the laminin α1 chain. AG73 peptide is known as a ligand for syndecans, one of the major heparin sulfate-containing transmembrane proteoglycans. Syndecan-2 is highly expressed in various cancer cells and plays a role in angiogenesis. In this study, we prepared AG73-labeled polyethyleneglycol-modified liposomes (AG73-PEG liposomes) for gene delivery tool to syndecan-2 overexpressing cancer cells, and assessed the characterization of AG73-PEG liposomes. We confirmed the conjugation of AG73 peptide to PEG liposomes by reverse-phase high-performance liquid chromatography analysis. Electron microscopy analysis showed that monodiseperse AG73-labeled lipsomes were prepared. We also assessed the gene transfection efficiency of AG73-PEG liposomes in syndecan-2 overexpressing cancer cells or syndecan-2 less expressing cancer cells. As a result, AG73-mediated liposomal gene transfection efficiency was increased by 100-fold in syndecan-2 overexpressing cancer cells compared to syndecan-2 less expressing cancer cells. These results suggested that AG73-PEG liposomes were successfully prepared from a point of view of the modification of AG73 peptide to PEG-liposomes and the particle size of liposomes, which presented nano size. Furthermore, our results suggest that AG73-PEG liposomes can be a useful targeted gene delivery vehicle for syndecan-2 overexpressing cancer cells.

Author-supplied keywords

  • Cell Line
  • Chromatography
  • DNA
  • DNA: administration & dosage
  • DNA: therapeutic use
  • Electron
  • Gene Transfer Techniques
  • Genetic Therapy
  • Genetic Therapy: methods
  • High Pressure Liquid
  • Humans
  • Laminin
  • Liposomes
  • Liposomes: administration & dosage
  • Liposomes: chemical synthesis
  • Microscopy
  • Neoplasms
  • Neoplasms: drug therapy
  • Neoplasms: metabolism
  • Particle Size
  • Peptide Fragments
  • Syndecan-2
  • Syndecan-2: metabolism
  • Transfection
  • Transfection: methods
  • Tumor
  • ag73 peptide
  • can selectively deliver therapeu-
  • delivery vehicles or vectors
  • gene delivery
  • in gene therapy
  • it is necessary that
  • liposome
  • syndecan
  • the development of

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  • Yoichi Negishi

  • Daiki Omata

  • Hiroshi Iijima

  • Nobuhito Hamano

  • Yoko Endo-Takahashi

  • Motoyoshi Nomizu

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