State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200032, People's Republic of China.
Langmuir. 2013 Jul 9;29(27):8683-93. doi: 10.1021/la401166v. Epub 2013 Jun 27.
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), ζ 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.
发展具有低细胞毒性的高稳定性和高效非病毒载体对于靶向肿瘤基因治疗非常重要。在这项研究中，从具有不同碳链（十二烷基、十四烷基、十六烷基和十八烷基）的季铵化（羧甲基）壳聚糖的聚合物表面活性剂制备了具有类似脂质双层结构和高热稳定性的阳离子聚合物脂质体（CPLs）。通过比较影响基因传递的不同因素，选择了具有合适尺寸（184.4±17.1nm）、ζ电位（27.5±4.9mV）和合成 TQCMC 的生产力（重量产率 13.1%）的十四烷基季铵化（羧甲基）壳聚糖（TQCMC）CPLs 用于各种癌细胞系的基因转染评估。尽管 TQCMC CPLs 在体外的基因转染效率低于阳离子脂质体（Lipofectamine 2000），但它们在静脉注射后体内对携带 U87 和 SMMC-7721 肿瘤的癌症组织具有更高的报告基因传递能力。TQCMC CPLs 还具有更低的细胞毒性和更低的细胞因子产生或肝损伤，用于 BALB/c 小鼠。我们得出结论，CPLs 是有前途的基因传递系统，可用于靶向各种癌症。
