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

Roberto Pallini, Carla L. Esposito, Silvia Nuzzo, Swati A. Kumar, Anna Rienzo, Clare L. Lawrence, Lisa Shaw, Jane E. Alder, Lucia Ricci-Vitiani, Silvia Catuogno, Vittorio De Franciscis

Research output: Contribution to journalArticle

50 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)43-57
Number of pages15
JournalJournal of Controlled Release
Volume238
DOIs
Publication statusPublished - 2016

Keywords

  • 3003
  • Aptamer
  • Cancer stem cells
  • Glioblastoma
  • Targeted delivery
  • microRNA

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