Nam Joung-Pyo, Nam Kihoon, Jung Simhyun, Nah Jae-Woon, Kim Sung Wan
Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, United States.
Department of Polymer Science and Engineering, Sunchon National University 255 Jungang-ro, Suncheon, Jeollanam-do, Republic of Korea.
J Control Release. 2015 Jul 10;209:179-85. doi: 10.1016/j.jconrel.2015.04.039. Epub 2015 Apr 30.
Small interfering ribonucleic acid (siRNA), 20-25 base pairs in length, can interfere with the expression of specific genes. Recently, many groups reported the therapeutic intervention of siRNA in various cancer cells. In this study, dendrimer type bio-reducible polymer (PAM-ABP) which was synthesized using arginine grafted bio-reducible poly(cystaminebisacrylamide-diaminohexane) (ABP) and polyamidoamine (PAMAM) was used to deliver anti-VEGF siRNA into cancer cell lines including human hepatocarcinoma (Huh-7), human lung adenocarcinoma (A549), and human fibrosarcoma (HT1080) cells and access their potential as a siRNA delivery carrier for cancer therapy. PAM-ABP and siRNA formed polyplexes with average diameter of 116 nm and charge of around +24.6 mV. The siRNA in the PAM-ABP/siRNA polyplex was released by 5mM DTT and heparin. VEGF gene silencing efficiency of PAM-ABP/siRNA polyplexes was shown to be more effective than PEI/siRNA polyplexes in three cell lines with the following order HT1080>A549>Huh-7.
长度为20 - 25个碱基对的小干扰核糖核酸(siRNA)能够干扰特定基因的表达。最近,许多研究小组报道了siRNA在多种癌细胞中的治疗干预作用。在本研究中,使用精氨酸接枝的生物可还原聚(胱胺双丙烯酰胺 - 二氨基己烷)(ABP)和聚酰胺 - 胺(PAMAM)合成的树枝状生物可还原聚合物(PAM - ABP)被用于将抗血管内皮生长因子(VEGF)的siRNA递送至包括人肝癌细胞系(Huh - 7)、人肺腺癌细胞系(A549)和人纤维肉瘤细胞系(HT1080)在内的癌细胞系中,并评估其作为癌症治疗中siRNA递送载体的潜力。PAM - ABP和siRNA形成了平均直径为116 nm、电荷约为 +24.6 mV的多聚体。PAM - ABP/siRNA多聚体中的siRNA可被5mM二硫苏糖醇(DTT)和肝素释放。在三种细胞系中,PAM - ABP/siRNA多聚体的VEGF基因沉默效率显示比聚乙烯亚胺(PEI)/siRNA多聚体更有效,顺序为HT1080 > A549 > Huh - 7。