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

表面修饰的LPC纳米粒介导的siRNA肿瘤靶向递送(英文)

作　　者：杨婷[1] 赵志霞[1] 徐振中[1] 赵恩宇[1] 刘晓岩[1] 陈成军[1] 王坚成[1] 张强[1] 

机构地区：[1]北京大学医学部药学院药剂学系,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2011年第6期590-596,共7页中国药学（英文版）

基　　金：National Basic Research Program of China(973 Program,Grant No.2007CB935800 and 2009CB930300);Beijing Natural Science foundation(Grant No.7112089)

摘　　要：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.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-PEG_(2000)或DSPE-PEG_(2000)-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-NP Chondroitin sulfate T7 peptide 

分 类 号：R730.2[医药卫生—肿瘤]