DNA polyplexes based on degradable oligoethylenimine-derivatives: combination with EGF receptor targeting and endosomal release functions.
Combination of the degradable polymeric gene carriers OEI-HD-1 and LT- OEI-HD-1 with an EGF targeting conjugate resulted in strongly (up to 900-fold) enhanced polyplex activity in EGF-receptor rich HUH7 hepatocellular carcinoma cells. The targeting ligand effect was DNA dose dependent, could be blocked by competitive receptor binding with unbound EGF ligand, and was not observed in receptor-negative control cells. Measures which enhance intracellular endosomal escape, either photochemically enhanced intracellular release (PCI) or the incorporation of a novel membrane-active melittin analog NMA-3, further enhanced gene transfer activity of EGF/OEI-HD-1 polyplexes.
Kloeckner
Julia
J
Pharmaceutical Biology-Biotechnology, Department of Pharmacy, Ludwig-Maximilians-Universität, Butenandtstr. 5-13, D-81377 Munich, Germany.
Boeckle
Sabine
S
Persson
Daniel
D
Roedl
Wolfgang
W
Ogris
Manfred
M
Berg
Kristian
K
Wagner
Ernst
E
D000818:Animals; D001667:Binding, Competitive; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000628:therapy; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000628:therapy; D008156:Luciferases; D008555:Melitten / Q000031:analogs & derivatives / Q000378:metabolism; D051379:Mice; D017319:Photosensitizing Agents / Q000494:pharmacology; D010957:Plasmids; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry*; D011166:Porphyrins / Q000494:pharmacology; D014162:Transfection / Q000379:methods*
C050105:N-methylanthraniloyl melitten; D017319:Photosensitizing Agents; D011166:Porphyrins; C425082:di(4-sulfonatophenyl)diphenylporphine; D008555:Melitten; D004815:Epidermal Growth Factor; D011094:Polyethyleneimine; D004247:DNA; D008156:Luciferases; D066246:ErbB Receptors