title: Polysaccharide nanogel gene delivery system with endosome-escaping function: Co-delivery of plasmid DNA and phospholipase A2.
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.
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Toita
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Sawada
authors.forename: Kazunari
authors.initials: K
authors.lastname: Akiyoshi
mesh_terms: D000818:Animals; D001516:Bees; D019556:COS Cells; D002412:Cations / Q000737:chemistry; D002522:Chlorocebus aethiops; D003505:Cyclodextrins / Q000737:chemistry*; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004337:Drug Carriers / Q000737:chemistry; D011992:Endosomes / Q000378:metabolism; D006461:Hemolysis; D008156:Luciferases / Q000235:genetics; D000080385:Nanogels; D054467:Phospholipases A2 / Q000008:administration & dosage* / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D012756:Sheep; D014162:Transfection
chemical_list: D002412:Cations; D003505:Cyclodextrins; D004337:Drug Carriers; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA; D008156:Luciferases; D054467:Phospholipases A2