Zhang Yangde, Zhang Yanqiong, Chen Jiji, Zhang Binghua, Pan Yifeng, Ren Lifeng, Zhao Jinfen, Luo Yulin, Zhai Denggao, Wang Shunwei, Wang Jiwei
National Hepatobiliary and Enteric Surgery Research Center, Central South University, Changsha, Hunan, China.
Nanomedicine. 2007 Jun;3(2):144-53. doi: 10.1016/j.nano.2007.01.004. Epub 2007 Apr 30.
To make progress toward an efficient gene vector for cancer gene therapy, a novel nonviral vector of polybutylcyanoacrylate nanoparticles (PBCA NPs) was developed. Cetyltrimethyl ammonium bromide (CTAB) was used to modify the surface of PBCA NPs, and then the plasmid DNA (pDNA) of pAFP-TK was wrapped into PBCA-CTAB NPs. Atomic force microscopy and zeta potential demonstrated that PBCA-CTAB NPs were 80-200 nm in diameter and had +15.6 mV positive surface charges. Assay using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide showed that PBCA-CTAB NPs had less cytotoxicity to 3T3 cells than HepG2 cells. The analysis of PBCA-CTAB-DNA complexes could not only protect DNA from degradation by DNase I, it could also transfer pDNA into targeted cells with high transfection efficiency. Furthermore, when PBCA-CTAB NPs combined with suicide gene pAFP-TK, alpha-fetoprotein-positive cells transfected by it were highly sensitive to ganciclovir treatment, and cell survival declined precipitously. Therefore, this target strategy using a pAFP-TK/GCV suicide gene therapy system in which PBCA-CTAB NPs serve as gene delivery vectors explores a promising area for alpha-fetoprotein-positive hepatocellular carcinoma and associated carcinoma therapy.
为了在癌症基因治疗的高效基因载体方面取得进展，开发了一种新型的聚氰基丙烯酸丁酯纳米颗粒（PBCA NPs）非病毒载体。使用十六烷基三甲基溴化铵（CTAB）修饰PBCA NPs的表面，然后将pAFP-TK的质粒DNA（pDNA）包裹到PBCA-CTAB NPs中。原子力显微镜和zeta电位表明，PBCA-CTAB NPs的直径为80-200 nm，表面带+15.6 mV的正电荷。使用3-（4,5-二甲基-2-噻唑基）-2,5-二苯基-2H-四唑溴盐的检测表明，PBCA-CTAB NPs对3T3细胞的细胞毒性低于对HepG2细胞的细胞毒性。对PBCA-CTAB-DNA复合物的分析不仅可以保护DNA不被DNase I降解，还可以将pDNA高效转染到靶细胞中。此外，当PBCA-CTAB NPs与自杀基因pAFP-TK结合时，被其转染的甲胎蛋白阳性细胞对更昔洛韦治疗高度敏感，细胞存活率急剧下降。因此，这种使用pAFP-TK/GCV自杀基因治疗系统，以PBCA-CTAB NPs作为基因递送载体的靶向策略，为甲胎蛋白阳性肝细胞癌及相关癌症的治疗探索了一个有前景的领域。
