Targeted gene delivery to hepatocytes with galactosylated amphiphilic cyclodextrins.
作者： Anthony McMahon , Martin J. O'Neill , Eva Gomez , Ruth Donohue , Damien Forde
DOI: 10.1111/J.2042-7158.2012.01497.X
关键词:
摘要: Objectives Achieving targeted delivery of gene medicines is desirable to maximise activity. Here, galactosylated amphiphilic cyclodextrins (CDs) are examined in terms their ability transfect asialoglycoprotein receptor-bearing HepG2 cells. Methods Cationic CDs were synthesised as well bearing galactose-targeting ligands with different linker lengths. Binding a galactose-specific lectin was by surface plasmon resonance. formulated and without the helper lipid DOPE complexed plasmid DNA. Transfection evaluated luciferase assay. Intracellular trafficking assessed confocal microscopy. Key findings achieved. decreased length between galactosyl group CD core. Contrary binding results, transfection levels increased an increase from 7 atoms 15. Compared non-targeted formulations, significant observed only presence DOPE. Confocal microscopy revealed that caused pronounced effect on cellular distribution. Conclusions The ligand induced substantial increases over formulations when included, indicating potential for using CD-based systems.
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