Tumor-targeted delivery of siRNA by surface-modified LPC nanoparticles

doi:10.5246/jcps.2011.06.076

Abstract

Abstract: 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-PEG2000 and DSPE-PEG2000-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.

Key words: siRNA, LPC-NP, Chondroitin sulfate, T7 peptide

CLC Number:

R943.42

Supporting:

Ting Yang, Zhi-Xia Zhao, Zhen-Zhong Xu, En-Yu Zhao, Xiao-Yan Liu, Cheng-Jun Chen, Jian-Cheng Wang^*, Qiang Zhang . Tumor-targeted delivery of siRNA by surface-modified LPC nanoparticles [J]. , DOI: 10.5246/jcps.2011.06.076.

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