表面修饰的LPC纳米粒介导的siRNA肿瘤靶向递送

doi:10.5246/jcps.2011.06.076

表面修饰的LPC纳米粒介导的siRNA肿瘤靶向递送

杨婷, 赵志霞, 徐振中, 赵恩宇, 刘晓岩, 陈成军, 王坚成^*, 张强

北京大学医学部药学院药剂学系, 北京 100191

收稿日期:2011-05-04 修回日期:2011-09-04 出版日期:2011-11-15 发布日期:2011-11-15
通讯作者: 王坚成*

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

Ting Yang, Zhi-Xia Zhao, Zhen-Zhong Xu, En-Yu Zhao, Xiao-Yan Liu, Cheng-Jun Chen, Jian-Cheng Wang^*, Qiang Zhang

Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2011-05-04 Revised:2011-09-04 Online:2011-11-15 Published:2011-11-15
Contact: Jian-Cheng Wang*

摘要/Abstract

摘要：

本研究构建了能够靶向肿瘤的新型纳米粒 (脂质体-鱼精蛋白-硫酸软骨素纳米粒, LPC-NP)。该纳米粒粒径约90 nm, zata电位约+35 mV。采用后插法对LPC纳米粒进行DSPE-PEG2000或DSPE-PEG2000-T7修饰。T7是与转铁蛋白功能类似的七肽, 能够靶向转铁蛋白受体过度表达的乳腺癌细胞MCF-7。PEG修饰可显著降低血清对LPC纳米粒的聚集作用, T7修饰的纳米粒显著提高siRNA的细胞摄取和基因沉默效率。体外细胞毒实验表明抗EGFR siRNA显著抑制MCF-7细胞生长。实验结果表明经T7肽修饰的LPC纳米粒有望成为RNA干扰肿瘤治疗的递送载体。

关键词: siRNA, LPC纳米粒, 硫酸软骨素, T7修饰

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

中图分类号:

R943.42

Supporting:

Foundation items: National Basic Research Program of China (973 Program, Grant No. 2007CB935800 and 2009CB930300) and Beijing Natural Science foundation (Grant No. 7112089).
^*Corresponding author. Tel.: 86-10-82802683

杨婷, 赵志霞, 徐振中, 赵恩宇, 刘晓岩, 陈成军, 王坚成^*, 张强

. 表面修饰的LPC纳米粒介导的siRNA肿瘤靶向递送[J]. , DOI: 10.5246/jcps.2011.06.076.

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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