Yu Yingting, Yao Yi, Yan Hao, Wang Rui, Zhang Zhenming, Sun Xiaodan, Zhao Lingyun, Ao Xiang, Xie Zhen, Wu Qiong
MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science & Engineering, Tsinghua University, Beijing, China.
Mol Ther Nucleic Acids. 2016 May 3;5(5):e318. doi: 10.1038/mtna.2016.28.
Targeted therapy for cancer is a research area of great interest, and magnetic nanoparticles (MNPs) show great potential as targeted carriers for therapeutics. One important class of cancer biomarkers is microRNAs (miRNAs), which play a significant role in tumor initiation and progression. In this study, a cascade recognition system containing multiple plasmids, including a Tet activator, a lacI repressor gene driven by the TetOn promoter, and a reporter gene repressed by the lacI repressor and influenced by multiple endogenous miRNAs, was used to recognize cells that display miRNA signals that are characteristic of cancer. For this purpose, three types of signal miRNAs with high proliferation and metastasis abilities were chosen (miR-21, miR-145, and miR-9). The response of this system to the human breast cancer MCF-7 cell line was 3.2-fold higher than that to the human breast epithelial HBL100 cell line and almost 7.5-fold higher than that to human embryonic kidney HEK293T cells. In combination with polyethyleneimine-modified MNPs, this recognition system targeted the tumor location in situ in an animal model, and an ~42% repression of tumor growth was achieved. Our study provides a new combination of magnetic nanocarrier and gene therapy based on miRNAs that are active in vivo, which has potential for use in future cancer therapies.
癌症的靶向治疗是一个备受关注的研究领域，磁性纳米颗粒（MNPs）作为治疗药物的靶向载体显示出巨大潜力。一类重要的癌症生物标志物是微小RNA（miRNAs），它们在肿瘤的发生和发展中起着重要作用。在本研究中，使用了一种包含多个质粒的级联识别系统，其中包括一个Tet激活剂、一个由TetOn启动子驱动的lacI阻遏基因，以及一个受lacI阻遏并受多种内源性miRNAs影响的报告基因，用于识别显示癌症特征性miRNA信号的细胞。为此，选择了三种具有高增殖和转移能力的信号miRNA（miR-21、miR-145和miR-9）。该系统对人乳腺癌MCF-7细胞系的反应比对人乳腺上皮HBL100细胞系高3.2倍，比对人胚肾HEK293T细胞高近7.5倍。与聚乙烯亚胺修饰的MNPs相结合，该识别系统在动物模型中原位靶向肿瘤部位，实现了约42%的肿瘤生长抑制。我们的研究提供了一种基于体内活性miRNAs的磁性纳米载体与基因治疗的新组合，具有在未来癌症治疗中应用的潜力。
