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通过全身注射携带配体和小干扰RNA的RNA纳米颗粒实现胃癌消退

Regression of Gastric Cancer by Systemic Injection of RNA Nanoparticles Carrying both Ligand and siRNA.

作者信息

Cui Daxiang, Zhang Chunlei, Liu Bing, Shu Yi, Du Tong, Shu Dan, Wang Kan, Dai Fangping, Liu Yanlei, Li Chao, Pan Fei, Yang Yuming, Ni Jian, Li Hui, Brand-Saberi Beate, Guo Peixuan

机构信息

Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, Bio-X center, National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.

Nanobiotechnology Center, Markey Cancer Center, and Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.

出版信息

Sci Rep. 2015 Jul 3;5:10726. doi: 10.1038/srep10726.

Abstract

Gastric cancer is the second leading cause of cancer-related death worldwide. RNA nanotechnology has recently emerged as an important field due to recent finding of its high thermodynamic stability, favorable and distinctive in vivo attributes. Here we reported the use of the thermostable three-way junction (3WJ) of bacteriophage phi29 motor pRNA to escort folic acid, a fluorescent image marker and BRCAA1 siRNA for targeting, imaging, delivery, gene silencing and regression of gastric cancer in animal models. In vitro assay revealed that the RNA nanoparticles specifically bind to gastric cancer cells, and knock-down the BRCAA1 gene. Apoptosis of gastric cancer cells was observed. Animal trials confirmed that these RNA nanoparticles could be used to image gastric cancer in vivo, while showing little accumulation in crucial organs and tissues. The volume of gastric tumors noticeably decreased during the course of treatment. No damage to important organs by RNA nanoparticles was detectible. All the results indicated that this novel RNA nanotechnology can overcome conventional cancer therapeutic limitations and opens new opportunities for specific delivery of therapeutics to stomach cancer without damaging normal cells and tissues, reduce the toxicity and side effect, improve the therapeutic effect, and exhibit great potential in clinical tumor therapy.

摘要

胃癌是全球癌症相关死亡的第二大主要原因。由于最近发现RNA纳米技术具有高热力学稳定性、良好且独特的体内特性,它已成为一个重要领域。在此,我们报告了利用噬菌体phi29马达pRNA的热稳定三向接头(3WJ)来护送叶酸、一种荧光图像标记物以及BRCAA1 siRNA,用于在动物模型中对胃癌进行靶向、成像、递送、基因沉默和消退。体外试验表明,RNA纳米颗粒特异性结合胃癌细胞,并敲低BRCAA1基因。观察到胃癌细胞发生凋亡。动物试验证实,这些RNA纳米颗粒可用于体内胃癌成像,同时在关键器官和组织中几乎没有积累。在治疗过程中,胃肿瘤体积明显减小。未检测到RNA纳米颗粒对重要器官造成损害。所有结果表明,这种新型RNA纳米技术可以克服传统癌症治疗的局限性,为向胃癌特异性递送治疗药物开辟新的机会,而不会损害正常细胞和组织,降低毒性和副作用,提高治疗效果,并在临床肿瘤治疗中展现出巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eee6/4490273/030bed00e62d/srep10726-f1.jpg

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