Polysaccharide nanogel gene delivery system with endosome-escaping function: Co-delivery of plasmid DNA and phospholipase A2

J Control Release. 2011 Oct 10;155(1):54-9. doi: 10.1016/j.jconrel.2010.12.008. Epub 2010 Dec 24.

Abstract

We developed a novel gene delivery system capable of endosome disruption using a polysaccharide-based cationic nanogel composed of a hexadecyl group-bearing cationic cycloamylose nanogel (C16-catCA nanogel) and phospholipaseA(2) (PLA(2)) to hydrolyze membrane phospholipids. C16-catCA nanogel formed nanoparticles with PLA(2) and pDNA by hydrophobic and electrostatic interactions. Both pDNA and PLA(2) were effectively internalized into cells by the C16-catCA nanogel. In addition, the pDNA expression level was enhanced when complexed with specific concentrations of PLA(2). PLA(2) complexed with C16-catCA nanogel also showed a similar hemolytic activity against red blood cells to that observed using native PLA(2). These results suggest that the C16-catCA nanogel/PLA(2) complex possesses membrane disruption ability when delivered into cells and triggers the subsequent release of pDNA from the endosome to the cytoplasm. This is the first report of co-delivery of pDNA and PLA(2) using the same carrier to achieve effective gene delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bees
  • COS Cells
  • Cations / chemistry
  • Chlorocebus aethiops
  • Cyclodextrins / chemistry*
  • DNA / administration & dosage*
  • DNA / genetics
  • Drug Carriers / chemistry
  • Endosomes / metabolism
  • Hemolysis
  • Luciferases / genetics
  • Nanogels
  • Phospholipases A2 / administration & dosage*
  • Phospholipases A2 / metabolism
  • Plasmids / administration & dosage*
  • Plasmids / genetics
  • Polyethylene Glycols / chemistry*
  • Polyethyleneimine / chemistry*
  • Sheep
  • Transfection*

Substances

  • Cations
  • Cyclodextrins
  • Drug Carriers
  • Nanogels
  • polyethylene glycol polyethyleneimine nanogel
  • Polyethylene Glycols
  • Polyethyleneimine
  • DNA
  • Luciferases
  • Phospholipases A2