With increasing knowledge of the molecular mechanisms of endogenous RNA interference,systemic delivery of small interfering RNA（siRNA） via targeted nanoparticles has emerged as a potential strategy for cancer gene therapy.In this study,a novel formulation[liposome-protamine-chondroitin sulfate nanoparticles（LPC-NP）]was developed for siRNA delivery by self-assembling with charge-charge interaction.The LPC-NP was further modified by DSPE-PEG_（2000） and DSPE-PEG_（2000）-T7 by the post-insertion method.T7,a transferrin-like seven-amino acid peptide,is a targeting ligand for transferrin receptor-overexpressed MCF-7 breast cancer cells.The particle size and zeta potential of LPC-NP were approximately 90 nm and ＋35 mV,respectively. It was shown that PEG modification could significantly decrease aggregation of LPC-NP in serum,and T7 peptide modified LPC-NP could significantly increase the cellular uptake and the gene-silencing effect of siRNA.In vitro cytotoxicity assay exhibited that significant cell growth inhibition was achieved in MCF-7 cells after the delivery of anti-EGFR siRNA.Our encouraging results suggested that T7-modified LPC-NP might be a promising carrier for RNAi-based tumor therapy.
