Angiogenesis is an attractive target for
cancer therapy, due to its central position in
tumor growth and development.
Vascular Endothelial Growth Factor (
VEGF) and its receptors (VEGFRs) play a key role in the angiogenic process. A promising strategy for targeting
VEGF-mediated angiogenesis is RNA interference (RNAi) using
short interfering RNA (
siRNA). However, for efficacious RNAi a well-designed
siRNA delivery system is crucial.
Liposome-Polycation-
DNA (LPD) particles form a promising system for
siRNA delivery to
tumors. In order to target angiogenic endothelial cells, LPD particles may be modified with a targeting
ligand, such as a cyclic
Arg-Gly-Asp (
RGD) peptide that specifically binds to
integrins expressed on
tumor-associated endothelial cells. In the current study, RGD-targeted PEGylated LPD particles containing
VEGFR-2 siRNA were prepared and optimized with respect to their size and charge by varying
protamine content, carrier
DNA content for stronger complexation, and PEGylation density. The size of the optimized particles was around 200 nm and the ΞΆ-potential was approximately +20 mV. The uptake and silencing efficacy of the RGD-targeted PEGylated LPD particles were evaluated in H5V cells (murine endothelial cells) and Human Umbilical Vein Endothelial cells (HUVECs). When compared to non-targeted LPD particles, enhanced uptake and silencing of
VEGFR-2 expression was observed for RGD-targeted PEGylated LPD particles. In conclusion, the RGD-targeted PEGylated LPD particles containing
VEGFR-2 siRNA presented here may be a promising approach for targeting
VEGF-mediated angiogenesis in
cancer therapy.