(208g) Effect of RGD to RGD Spacing On Clustered Ligand Targeted Non-Viral Vectors

Ng, Q. - Presenter, University of California, Los Angeles (UCLA)

We previously demonstrated that clustered Arg-Gly-Asp (RGD) peptides ligands could be introduced into DNA/polyethylene imine polyplexes through the use of RGD modified gold nanoparticles [1]. These clustered ligands were demonstrated to not only enhance non-viral gene transfer in vitro but also targeting towards tumors with high αvβ3 intergrin expression in vivo. In our present study, we investigated the effect of RGD to RGD spacing to the efficiency of gene transfer in vitro. Spacing was modulated by using gold nanoparticles of various core sizes and different peptide ratios. Spacing's ranging from 3 to 15 nm was studied using 5 nm and 10 nm gold nanoparticle cores. Through these studies we show that the ligand spacing is an important parameter to modulate for the enhancement of gene transfer in this system.

1. Ng, Q. K. T., Sutton, M. K., Soonsawad, P., Xing, L., Cheng, H., and Segura, T. (2009). Engineering Clustered Ligand Binding Into Nonviral Vectors: αvβ3 Targeting as an Example. Mol. Ther.