Improvement of targeted gene delivery to human cancer cells by a novel trifunctional crosslinker.
A facile method for the construction of an immunoconjugate which displays targeting ligands, such as antibody fragments, with a high density is reported. For this purpose, we synthesized a novel trifunctional crosslinking reagent. By the use of this reagent, ligands targeting the specific cell can be displayed on the surface of the drug carrier with a high density. In this study, we display HER2 (human epidermal growth-factor receptor-2) binding ligands on branched polyethylenimine (PEI), which can form polyplexes with plasmid DNA. Kinetic analysis of the binding to the extracellular domain of HER2 show the PEI displaying a high density of ligands binds to the target more strongly compared to the PEI displaying ligands at a low density. The increased density of HER2 ligands displayed on the gene carrier contributes to the improved transfection efficiency. This approach can be applied to other drug delivery systems, including liposome, micelle, and so on.
Shiota
Maki
M
National Institute of Advanced Industrial Science and Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562, Japan.
Shamsur
Lahman
L
Kawahara
Shun-ichi
S
Wadhwa
Renu
R
Ikeda
Yutaka
Y
D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry*; D015316:Genetic Therapy; D006801:Humans; D007094:Imides / Q000138:chemical synthesis / Q000737:chemistry*; D008024:Ligands; D008081:Liposomes; D009369:Neoplasms / Q000628:therapy*; D011094:Polyethyleneimine / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D014162:Transfection
D003432:Cross-Linking Reagents; D007094:Imides; D008024:Ligands; D008081:Liposomes; D011094:Polyethyleneimine; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human