Journal
JOURNAL OF CONTROLLED RELEASE
Volume 238, Issue -, Pages 43-57Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2016.07.032
Keywords
Aptamer; Cancer stem cells; Glioblastoma; microRNA; Targeted delivery
Funding
- AIRC [13345, 9980, 15584, 14574]
- Italian Ministry of Economy and Finance
- Italian Ministry of Health [GR-2011-02352546]
- Brain Tumour North-West and In Between Ears Charity
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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.
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