RGD Conjugated Dendritic Polylysine for Cellular Delivery of Antisense Oligonucleotide

Dendritic polylysines (DPL) are highly branched nano-sized spherical polymer with positively charged primary amino groups on surface. This structural feature is useful for a delivery of antisense oligonucleotide or siRNA. In this study, we modified the surface of DPL with cyclic RGD (and iRGD) peptide by conjugation reaction generating RGD (and iRGD) peptide conjugated dendritic poly-lysines, RGD-DPL or iRGD-DPL. The prepared conjugates were evaluated for integrin receptor-mediated cellular delivery of antisense oligonucleotide. The conjugation of RGD or iRGD peptide on DPL was monitored by measuring the retention time in capillary zone electrophoresis and the absorbance at UV-Vis spectroscopy. Cellular delivery by DPL-RGD (or -iRGD)/antisense oligonucleotide complex was examined by antisense splicing correction assay on integrin alpha v/beta 3 positive A375B3-Luc cells, which were stably transfected with plasmid pLuc/705. DPL-RGD (or -iRGD)/antisense oligonucleotide complexes exhibited integrin receptor mediated uptake on A375B3 cells without inducing cellular toxicity. In addition, the delivery of antisense oligonucleotide was integrin receptor-dependent with moderate efficiency.