College of Chemical Engineering, Huaqiao University, Xiamen, 361021, People's Republic of China.
Fujian Provincial Key Laboratory of Biochemical Technology, Huaqiao University, Xiamen, 361021, People's Republic of China.
Microb Cell Fact. 2017 Nov 28;16(1):216. doi: 10.1186/s12934-017-0830-6.
Gene therapy has gained an increasing interest in its anti-tumor efficiency. However, numerous efforts are required to promote them to clinics. In this study, a novel and efficient delivery platform based on bacterial magnetosomes (BMs) were developed, and the efficiency of BMs in delivering small interfering ribonucleic acid (siRNA) as well as antiproliferative effects in vitro were investigated.
Initially, we optimized the nitrogen/phosphate ratio and the BMs/siRNA mass ratio as 20 and 1:2, respectively, to prepare the BMs-PEI-siRNA composites. Furthermore, the prepared nanoconjugates were systematically characterized. The dynamic light scattering measurements indicated that the particle size and the zeta potential of BMs-PEI-siRNA are 196.5 nm and 49.5 ± 3.77 mV, respectively, which are optimum for cell internalization. Moreover, the confocal laser scanning microscope observations showed that these composites were at a proximity to the nucleus and led to an effective silencing effect. BMs-PEI-siRNA composites efficiently inhibited the growth of HeLa cells in a dose-as well as time-dependent manner. Eventually, a dual stain assay using acridine orange/ethidium bromide, revealed that these nanocomposites induced late apoptosis in cancer cells.
A novel and efficient gene delivery system based on BMs was successfully produced for cancer therapy, and these innovative carriers will potentially find widespread applications in the pharmaceutical field.
基因治疗因其抗肿瘤效率而受到越来越多的关注。然而,需要大量的努力才能将其推向临床。在这项研究中,开发了一种基于细菌磁小体(BMs)的新型高效递药平台,并研究了 BMs 传递小干扰核糖核酸(siRNA)的效率及其体外抗增殖作用。
首先,我们将氮/磷比和 BMs/siRNA 质量比优化为 20 和 1:2,以制备 BMs-PEI-siRNA 复合物。此外,还对制备的纳米复合物进行了系统表征。动态光散射测量表明,BMs-PEI-siRNA 的粒径和 Zeta 电位分别为 196.5nm 和 49.5±3.77mV,最有利于细胞内化。此外,共聚焦激光扫描显微镜观察表明,这些复合物接近细胞核,并导致有效的沉默效果。BMs-PEI-siRNA 复合物能够有效地抑制 HeLa 细胞的生长,具有剂量和时间依赖性。最终,使用吖啶橙/溴化乙锭的双重染色试验表明,这些纳米复合物诱导癌细胞晚期凋亡。
成功制备了一种基于 BMs 的新型高效基因传递系统,用于癌症治疗,这些创新载体将有望在制药领域得到广泛应用。