The clinical application of small interference RNA (siRNA) has been restricted by poor intracellular uptake, low serum stability, non-targeting property et al.During last decades, a lot of effort has been devoted to explore materials for siRNA delivery.In this study, a biodegradable, tumor-targeted, peptide self-assembled nanoparticles (NPs) (c(RGDfk)-PEG-MAL hereinafter referred to as RPM) was found to be an effective siRNA carrier both in vitro and in vivo.The characterizations of the NPs were well studied by transmission electron microscopy (TEM), circular dichroism (CD) spectrum and dynamic light scattering (DLS).Studies in vitro demonstrated that RPM/VEGFR2-siRNA NPs are negligible cytotoxicity and can lead to gene silencing in HUVECs effectively.The study on zebra-fish showed its inhibition of neovascularization.And studies on animal model of tumor bearing nude mice indicated that it can significantly inhibit the tumor growth, remarkably reduce the vessels in tumor tissue, and down VEGFR2 (mRNA and protein) expression obviously.Furthermore, no immunogenicity was found by ELISA assay suggested RPM is negligible biological toxicity in vivo.In conclusion, RPM may provide a safe and effective delivery vector for the clinical application of siRNA in the near future.