Esposito, C.L., Nuzzo, S., Kumar, S.A., Rienzo, A., Lawrence, C.L., Pallini, R., Shaw, L., Alder, J.E., Ricci-Vitiani, L., Catuogno, S., de Franciscis, V.
A combined microRNA-based targeted therapeutic approach to eradicate glioblastoma stem-like cells
(2016) Journal of Controlled Release, 238, pp. 43-57.
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84979645423&partnerID=40&md5=e6e2a50bdbe5bc664a5fcc89b202676b
DOI: 10.1016/j.jconrel.2016.07.032
AFFILIATIONS: Istituto di Endocrinologia ed Oncologia Sperimentale “G. Salvatore”, CNR, Naples, Italy;
School of Pharmacy & Biomedical Sciences, University of Central Lancashire, Preston, United Kingdom;
Institute of Neurosurgery, Università Cattolica del Sacro Cuore, Rome, Italy;
Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Rome, Italy
ABSTRACT: 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. © 2016
CORRESPONDENCE ADDRESS: de Franciscis, V.; IEOS-CNR, Via T. de Amicis 95, Italy; email: defranci@unina.it
