Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore", CNR, Naples, Italy.
School of Pharmacy & Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK.
J Control Release. 2016 Sep 28;238:43-57. doi: 10.1016/j.jconrel.2016.07.032. Epub 2016 Jul 21.
A minor population of glioblastoma stem-like cells (GSCs) has been implicated in the relapse and resistance of glioblastoma to therapeutic treatments. Based on knowledge of the involvement of multiple microRNAs in GSC propagation, we designed a combinational approach to target the GSC population with multiple miRNA-based therapeutics. As carriers for the targeted delivery we took advantage of two aptamers that bind to, and inhibit, the receptor tyrosine kinases, Axl and PDGFRβ. We showed that the aptamer conjugates are transported through an in vitro blood-brain barrier (BBB) model. Furthermore, combining miR-137 and antimiR-10b synergizes with the receptor inhibitory function of aptamer carriers and prevents GSC expansion. Results highlighted the potential of combining multifunctional RNA-based therapeutics for selective targeting of GSCs and offer a proof of principle strategy to potentially fulfill the still unmet need for effective and safe treatment of glioma.
一小部分神经胶质瘤干细胞（GSCs）被认为与神经胶质瘤对治疗的复发和耐药有关。基于多种 microRNAs 参与 GSC 增殖的知识，我们设计了一种联合方法，用多种基于 microRNA 的治疗方法靶向 GSC 群体。作为靶向递送的载体，我们利用了两种能够结合并抑制受体酪氨酸激酶 Axl 和 PDGFRβ 的适体。我们表明，适体缀合物可以通过体外血脑屏障（BBB）模型进行运输。此外，miR-137 和 antimiR-10b 的联合作用与适体载体的受体抑制功能协同作用，防止 GSC 扩增。研究结果强调了联合使用多功能 RNA 治疗方法靶向 GSCs 的潜力，并为潜在地满足有效和安全治疗神经胶质瘤的未满足需求提供了一种原理验证策略。
