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Improvement of targeted gene delivery to human cancer cells by a novel trifunctional crosslinker.
Chem Asian J. 2009 Aug 3;4(8):1318-22
Authors: Shiota M, Shamsur L, Kawahara S, Wadhwa R, Ikeda Y
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.
PMID: 19579256 [PubMed - indexed for MEDLINE]
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