title: A combined microRNA-based targeted therapeutic approach to eradicate glioblastoma stem-like cells.
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.
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore", CNR, Naples, Italy.
authors.forename: Carla L
authors.initials: CL
authors.lastname: Esposito
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore", CNR, Naples, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Nuzzo
authors.affiliation: School of Pharmacy & Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK.
authors.forename: Swati A
authors.initials: SA
authors.lastname: Kumar
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore", CNR, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Rienzo
authors.affiliation: School of Pharmacy & Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Lawrence
authors.affiliation: Institute of Neurosurgery, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pallini
authors.affiliation: School of Pharmacy & Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Shaw
authors.affiliation: School of Pharmacy & Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Alder
authors.affiliation: Istituto Superiore di Sanità, Department of Hematology, Oncology and Molecular Medicine, Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Ricci-Vitiani
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore", CNR, Naples, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Catuogno
authors.affiliation: Istituto di Endocrinologia ed Oncologia Sperimentale "G. Salvatore", CNR, Naples, Italy. Electronic address: defranci@unina.it.
authors.forename: Vittorio
authors.initials: V
authors.lastname: de Franciscis
mesh_terms: D000070416:Antagomirs / Q000235:genetics / Q000627:therapeutic use*; D052157:Aptamers, Nucleotide / Q000378:metabolism / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000627:therapeutic use*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D000070416:Antagomirs; D052157:Aptamers, Nucleotide; C547183:MIRN10 microRNA, human; C545567:MIRN137 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human
keywords: Aptamer; Cancer stem cells; Glioblastoma; Targeted delivery; microRNA