MPEG-CS/Bmi-1RNAi Nanoparticles Synthesis and Its Targeted Inhibition Effect on CD133+ Laryngeal Stem Cells
MPEG-CS/Bmi-1RNAi Nanoparticles Synthesis and Its Targeted Inhibition Effect on CD133+ Laryngeal Stem Cells
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DOI：
10.1166/jnn.2018.14303
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发表时间：
2018-03-01
影响因子：
--
通讯作者：
Wang, Wei
中科院分区：
文献类型：
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作者：
Wei, Xudong;He, Jian;Wang, Wei
以往的研究证实，喉癌组织中的CD 133（+）细胞具有肿瘤干细胞的特征。Bmi-1基因表达是CD 133（+）细胞致瘤性的核心。在本研究中，我们尝试使用壳聚糖-甲氧基聚乙烯纳米颗粒（CS-mPEG-NPs）开发一种新的siRNA载体系统，其在CD 133（+）肿瘤干细胞中表现出更高的肿瘤靶向能力和增强的基因沉默功效。希望能阻断喉癌干细胞的自我更新，杀死喉癌干细胞。合成mPEG-CS-Bmi-1 RNAi纳米粒并检测其性质。观察Bmi-1基因沉默后CD 133（+）Hep-2肿瘤细胞侵袭能力及对放化疗敏感性的变化。本实验合成的mPEG-CS-Bmi-1 RNAi-NPs呈规则球形，平均粒径为139.70 ± 6.40 nm，包封率为85.21 ± 1.94%，载药量为18.47 ± 1.83%，细胞毒性低，对负载的基因具有良好的保护作用，抗核酸酶降解能力强，基因转染效率高。Bmi-1基因沉默后，CD 133（+）细胞的侵袭能力减弱。与紫杉醇共培养的CD 133（+）Bmi-1 RNAi细胞存活率较低。放疗后，CD 133（+）/Bmi-1 RNAi细胞的平均生长抑制率明显低于CD 133（+）细胞。结论：mPEG-CS纳米载体是一种理想的基因治疗载体，而沉默Bmi-1基因可增强CD 133（+）肿瘤干细胞对放化疗的敏感性，降低其侵袭能力。
Previous studies have confirmed that CD133(+) cells in laryngeal tumor tissue have the characteristics of cancer stem cells. Bmi-1 gene expression is central to the tumorigenicity of CD133(+) cells. In this study, we tried to develop a new siRNA carrier system using chitosan-methoxypolyethylene nanoparticles (CS-mPEG-NPs) that exhibit higher tumor-targeting ability and enhanced gene silencing efficacy in CD133(+) tumor stem cells. It is hoped to block the self-renewal and kill the stem cells of laryngeal carcinoma. The mPEG-CS-Bmi-1RNAi-NPs were synthesized and their characters were checked. The changes in invasion ability and sensitivity to radiotherapy and chemotherapy of CD133(+) Hep-2 tumor cells were observed after Bmi-1 gene silencing. The mPEG-CS-Bmi-1RNAi-NPs synthesized in this experiment have a regular spherical form, a mean size of 139.70 +/- 6.40 nm, an encapsulation efficiency of 85.21 +/- 1.94%, with drug loading capacity of 18.47 +/- 1.83%, as well as low cytotoxicity, providing good protection to the loaded gene, strong resistance to nuclease degradation and high gene transfection efficiency. After Bmi-1 gene silencing, the invasion ability of CD133(+) cells was weakened. Co-cultured with paclitaxel, the survival rates of CD133(+) Bmi-1RNAi cells were lower. After radiotherapy, the mean growth inhibition rate of CD133(+)/Bmi-1RNAi cells was significantly lower than CD133(+) cells. In conclusion, the mPEG-CS nano-carrier is an ideal vector in gene therapy, while silencing the Bmi-1 gene can enhance the sensitivity of CD133(+) tumor stem cells to chemoradiotherapy and abate their invasion ability.