A combined microRNA-based targeted therapeutic approach to eradicate glioblastoma stem-like cells

被引：69
作者：
Esposito, Carla L. [1 ]
Nuzzo, Silvia [1 ]
Kumar, Swati A. [2 ]
Rienzo, Anna [1 ]
Lawrence, Clare L. [2 ]
Pallini, Roberto [3 ]
Shaw, Lisa [2 ]
Alder, Jane E. [2 ]
Ricci-Vitiani, Lucia [4 ]
Catuogno, Silvia [1 ]
de Franciscis, Vittorio [1 ]
机构：
[1] CNR, Ist Endocrinol & Oncol Sperimentale G Salvatore, Naples, Italy
[2] Univ Cent Lancashire, Sch Pharm & Biomed Sci, Preston PR1 2HE, Lancs, England
[3] Univ Cattolica Sacro Cuore, Inst Neurosurg, Rome, Italy
[4] Ist Super Sanita, Dept Hematol Oncol & Mol Med, Rome, Italy
来源：
JOURNAL OF CONTROLLED RELEASE | 2016年 / 238卷
关键词：
Aptamer; Cancer stem cells; Glioblastoma; microRNA; Targeted delivery; APTAMER; GROWTH; SIRNA; CLASSIFICATION; RESISTANCE; PROGNOSIS; MECHANISM; AXL;
D O I：
10.1016/j.jconrel.2016.07.032
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
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 PDGFR beta. 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. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码：43 / 57
页数：15
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