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Article

Combined Targeting of Glioblastoma Stem-Like Cells by Neutralizing RNA-Bio-Drugs for STAT3

1
Istituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (CNR), 80145 Naples, Italy
2
IRCCS SDN (Istituto di Ricovero e Cura a Carattere Scientifico, SYNLAB istituto di Diagnostica Nucleare), 80143 Naples, Italy
3
Department of Molecular Medicine and Medical Biotechnology, “Federico II” University of Naples, 80131 Naples, Italy
4
Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
5
Institute of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
6
IRCCS Neuromed (Istituto di Ricovero e Cura a Carattere Scientifico Neuromed)—Istituto Neurologico Mediterraneo, 86077 Pozzilli, Italy
*
Authors to whom correspondence should be addressed.
Cancers 2020, 12(6), 1434; https://doi.org/10.3390/cancers12061434
Received: 22 April 2020 / Revised: 21 May 2020 / Accepted: 28 May 2020 / Published: 31 May 2020
(This article belongs to the Special Issue The Role of Aptamers in Cancer Diagnostics and Therapy)
An important drawback in the management of glioblastoma (GBM) patients is the frequent relapse upon surgery and therapy. A likely explanation is that conventional therapies poorly affect a small population of stem-like cancer cells (glioblastoma stem cells, GSCs) that remain capable of repopulating the tumour mass. Indeed, the development of therapeutic strategies able to hit GSCs while reducing the tumour burden has become an important challenge to increase a patient’s survival. The signal transducer and activator of transcription-3 (STAT3) has been reported to play a pivotal role in maintaining the tumour initiating capacity of the GSC population. Therefore, in order to impair the renewal and propagation of the PDGFRβ-expressing GSC population, here we took advantage of the aptamer–siRNA chimera (AsiC), named Gint4.T-STAT3, that we previously have shown to efficiently antagonize STAT3 in subcutaneous PDGFRβ-positive GBM xenografts. We demonstrate that the aptamer conjugate is able to effectively and specifically prevent patient-derived GSC function and expansion. Moreover, because of the therapeutic potential of using miR-10b inhibitors and of the broad expression of the Axl receptor in GBM, we used the GL21.T anti-Axl aptamer as the targeting moiety for anti-miR-10b, showing that, in combination with the STAT3 AsiC, the aptamer–miR-10b antagonist treatment further enhances the inhibition of GSC sphere formation. Our results highlight the potential to use a combined approach with targeted RNA therapeutics to inhibit GBM tumour dissemination and relapse. View Full-Text
Keywords: aptamer; cancer stem cells; glioblastoma; STAT3; targeted delivery aptamer; cancer stem cells; glioblastoma; STAT3; targeted delivery
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MDPI and ACS Style

Esposito, C.L.; Nuzzo, S.; Ibba, M.L.; Ricci-Vitiani, L.; Pallini, R.; Condorelli, G.; Catuogno, S.; de Franciscis, V. Combined Targeting of Glioblastoma Stem-Like Cells by Neutralizing RNA-Bio-Drugs for STAT3. Cancers 2020, 12, 1434. https://doi.org/10.3390/cancers12061434

AMA Style

Esposito CL, Nuzzo S, Ibba ML, Ricci-Vitiani L, Pallini R, Condorelli G, Catuogno S, de Franciscis V. Combined Targeting of Glioblastoma Stem-Like Cells by Neutralizing RNA-Bio-Drugs for STAT3. Cancers. 2020; 12(6):1434. https://doi.org/10.3390/cancers12061434

Chicago/Turabian Style

Esposito, Carla L.; Nuzzo, Silvia; Ibba, Maria L.; Ricci-Vitiani, Lucia; Pallini, Roberto; Condorelli, Gerolama; Catuogno, Silvia; de Franciscis, Vittorio. 2020. "Combined Targeting of Glioblastoma Stem-Like Cells by Neutralizing RNA-Bio-Drugs for STAT3" Cancers 12, no. 6: 1434. https://doi.org/10.3390/cancers12061434

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