Zinc-chelated poly(1-vinylimidazole) and a carbohydrate ligand polycation form DNA ternary complexes for gene delivery

Bioconjug Chem. 2011 Sep 21;22(9):1864-8. doi: 10.1021/bc2003378. Epub 2011 Aug 25.

Abstract

Zinc-chelated poly(1-vinylimidazole) (PVIm-Zn) and a carbohydrate ligand polycation, a poly(l-lysine) conjugated with lactose molecules (PLL-Lac), have formed DNA ternary complexes for gene delivery. The particle size of the PVIm-Zn/DNA complexes with negative zeta potential was decreased by the addition of the PLL-Lac. The resulting PLL-Lac/PVIm-Zn/DNA ternary complexes, which exhibited the pH-dependent dissociation of the PLL-Lac, mediated more gene expression than the PVIm/DNA binary complexes. The PLL-Lac/PVIm-Zn/DNA complexes with the specific recognition of cell surface receptors mediated the highest gene expression without cytotoxicity at a relatively lower charge ratio (positive/negative = 2.5). These results suggest that the pH-dependent dissociation of the carbohydrate ligands after the recognition of cell surface receptors, including the physicochemical and biochemical function of PVIm-Zn, played an important role in gene expression.

MeSH terms

  • Amino Acid Sequence
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival
  • Chelating Agents / chemistry
  • DNA / administration & dosage*
  • Gene Expression
  • Gene Transfer Techniques*
  • Humans
  • Hydrogen-Ion Concentration
  • Imidazoles / chemistry*
  • Lactose / chemistry
  • Ligands
  • Molecular Sequence Data
  • Polyamines
  • Polyelectrolytes
  • Polylysine / chemistry
  • Polyvinyls / chemistry*
  • Zinc / chemistry*

Substances

  • Antineoplastic Agents
  • Chelating Agents
  • Imidazoles
  • Ligands
  • Polyamines
  • Polyelectrolytes
  • Polyvinyls
  • poly(1-vinylimidazole)
  • polycations
  • Polylysine
  • DNA
  • Lactose
  • Zinc