Properties and Evaluation of Quaternized Chitosan/Lipid Cation Polymeric Liposomes for Cancer-Targeted Gene Delivery
Properties and Evaluation of Quaternized Chitosan/Lipid Cation Polymeric Liposomes for Cancer-Targeted Gene Delivery
复制标题
用于癌症靶向基因递送的季铵化壳聚糖/脂质阳离子聚合物脂质体的特性和评价
DOI：
10.1021/la401166v
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发表时间：
2013-07-09
期刊：
影响因子：
3.9
通讯作者：
Li, Zonghai
中科院分区：
文献类型：
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作者：
Liang, Xiaofei;Li, Xiaoyu;Li, Zonghai
开发稳定、高效、低细胞毒性的非病毒载体对肿瘤靶向基因治疗具有重要意义。以不同碳链（十二烷基、十四烷基、十六烷基和十八烷基）的季铵化（羧甲基）壳聚糖为高分子表面活性剂，制备了具有相似脂双层结构和高热稳定性的阳离子聚合物脂质体（CPLs）。通过比较影响基因递送的不同因素，选择具有合适尺寸（184.4 +/- 17.1 nm）、zeta电位（27.5 +/- 4.9 mV）和合成产率的十四烷基季铵化（羧甲基）壳聚糖（TQCMC）CPL（重量产率13.1%）用于各种癌细胞系的基因转染评估。尽管TQCMC CPL在体外的基因转染效率低于阳离子脂质体（Lipofectamine 2000），但静脉注射后，TQCMC CPL在体内对癌组织（荷U87和SMMC-7721肿瘤）显示出更高的报告基因递送能力。TQCMC CPL还具有较低的细胞毒性和较低的细胞因子产生或对BALB/c小鼠的肝损伤。我们的结论是，CPL是有前途的基因传递系统，可用于靶向各种癌症。
Development of high-stability and efficient nonviral vectors with low cytoxicity is important for targeted tumor gene therapy. In this study, cationic polymeric liposomes (CPLs), with similar lipid bilayer structure and high thermal stability, were prepared from polymeric surfactants of quaternized (carboxymethyl)chitosan with different carbon chains (dodecyl, tetradecyl, hexadecyl, and octadecyl). By comparing different factors that influence gene delivery, tetradecyl-quaternized (carboxymethy)chitosan (TQCMC) CPLs, with suitable size (184.4 +/- 17.1 nm), zeta potentials (27.5 +/- 4.9 mV), and productivity for synthesis TQCMC (weight yield 13.1%), were selected for gene transfection evaluation in various cancer cell lines. Although TQCMC CPLs have lower gene transfection efficiency compared with cationic liposomes (Lipofectamine 2000) in vitro, they displayed higher reporter gene delivery ability for cancer tissues (bearing U87 and SMMC-7721 tumors) in vivo after intravenous injection. TQCMC CPLs also have lower cell cytotoxicity and lower cytokine production or liver injury for BALB/c mice. We conclude that the CPLs are promising gene delivery systems that may be used to target various cancers.