期刊
JOURNAL OF CONTROLLED RELEASE
卷 210, 期 -, 页码 147-159出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2015.05.276
关键词
Aptamer; AntimiR; Targeted delivery; Cancer; Therapy
资金
- MERIT [RBNE08YFN3_001]
- AIRC [13345]
- Italian Ministry of Economy and Finance
- Grant CNR Medicina Personalizzata
- Compagnia San Paolo [2011.1172]
- CNR Flagship Project NanoMax (DESIRED) [2012-2014]
- Italian Ministry of Health [GR-2011-02352546]
Development of RNA-based antagonists (antimiRs) for disease-associated miRNAs in specific cell types or tissues has recently become a promising approach for treating several pathological conditions, including cancer. In order to explore the use of RNA-aptamers as carriers for cell-targeted delivery of antimiRs, here we designed two different conjugates using as carrier two aptamers that bind and antagonize cancer-associated receptor tyrosine kinases, Axl and PDGFRa. We conjugated the tumor suppressor antimiR-222 to each aptamer demonstrating: 1) effective and selective delivery to receptor-expressing tumor cells, 2) increased expression of miR-222 target mRNAs, and 3) functional synergy between the kinase inhibitory aptamer and the antimiR antagonizing functions. Furthermore, we generated modular molecules in which two different antimiR sequences connected in tandem are conjugated to a unique carrier aptamer. We proved this strategy to be effective to deplete multiple microRNAs simultaneously, thus combining the effects of different antimiRs without losing the cell targeting specificity. (C) 2015 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据