PEI-g-PEG-RGD/pCMV-sFlt-1 complex for targeted tumor therapy

Abstract

Vascular endothelial growth factor (VEGF) is overexpressed in most tumors and closely associated with tumor growth and metastasis. It has been shown that a soluble fragment of VEGF receptor Flt-1 (sFlt-1) has anti-angiogenic properties by way of its antagonist activity against VEGF. In the present study, a targeted polymeric gene delivery system, PEI-g-PEG-RGD, was developed by incorporating the ανβ3/ανβ5 integrin-binding RGD peptide, to the cationic polymer, PEI via a hydrophilic PEG spacer. The complex of sFlt-1 gene with PEI-g-PEG-RGD conjugate efficiently inhibited the proliferation of cultured endothelial cells. Moreover, PEI-g-PEG-RGD/pCMV-sFlt-1 complex repeatedly injected systemically showed the tumor regression effect in vivo tumor model.