Citation:

Boron clusters (ferrabisdicarbollides) shaping the future as radiosensitizers for multimodal (chemo/radio/PBFR) therapy of glioblastoma, Nuez-Martínez, Miquel, Queralt-Martín María, Muñoz-Juan Amanda, Aguilella {Vicente M. }, Laromaine Anna, Teixidor Francesc, Viñas Clara, Pinto {Catarina G. }, Pinheiro Teresa, Guerreiro {Joana F. }, Mendes Filipa, Roma-Rodrigues Catarina, Baptista {Pedro V. }, Fernandes {Alexandra R. }, Valic Srecko, and Marques Fernanda , Journal of Materials Chemistry B, dec, Volume 10, Number 47, p.9794–9815, (2022)

Abstract:

Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, and is highly resistant to conventional radiotherapy and chemotherapy. Therefore, the development of multidrug resistance and tumor recurrence are frequent. Given the poor survival with the current treatments, new therapeutic strategies are urgently needed. Radiotherapy (RT) is a common cancer treatment modality for GBM. However, there is still a need to improve RT efficiency, while reducing the severe side effects. Radiosensitizers can enhance the killing effect on tumor cells with less side effects on healthy tissues. Herein, we present our pioneering study on the highly stable and amphiphilic metallacarboranes, ferrabis(dicarbollides) ([o-FESAN]− and [8,8′-I2-o-FESAN]−), as potential radiosensitizers for GBM radiotherapy. We propose radiation methodologies that utilize secondary radiation emissions from iodine and iron, using ferrabis(dicarbollides) as iodine/iron donors, aiming to achieve a greater therapeutic effect than that of a conventional radiotherapy. As a proof-of-concept, we show that using 2D and 3D models of U87 cells, the cellular viability and survival were reduced using this treatment approach. We also tested for the first time the proton boron fusion reaction (PBFR) with ferrabis(dicarbollides), taking advantage of their high boron (11B) content. The results from the cellular damage response obtained suggest that proton boron fusion radiation therapy, when combined with boron-rich compounds, is a promising modality to fight against resistant tumors. Although these results are encouraging, more developments are needed to further explore ferrabis(dicarbollides) as radiosensitizers towards a positive impact on the therapeutic strategies for GBM.

Notes:

info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04349%2F2019/PT# info:eu-repo/grantAgreement/FCT/3599-PPCDT/UTAP-EXPL%2FFMT%2F0020%2F2021/PT# info:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FBTM-TEC%2F29256%2F2017/PT# info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04565%2F2020/PT# info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT# info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT# Funding Information: The authors received support from the Spanish Ministerio de Economía y Competitividad (PID2019-106832RB-100), the Generalitat de Catalunya (2017SGR1720), FCT - Funda{\c c}ão para a Ciência e a Tecnologia, in the scope of the projects LISBOA-01-0247-FEDER-045904, and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB. The Metrology Laboratory of Ionizing Radiation team of Centro Tecnológico e Nuclear, Instituto Superior Técnico (CTN/IST) is acknowledged for their support in the irradiation setups. Miquel Nuez-Martínez is enrolled in the PhD program of the UAB. MQM and VMA acknowledge financial support by the Spanish Government MCIN/AEI/10.13039/501100011033 (project 2019-108434GB-I00 to VMA and project IJC2018-035283-I to MQM), and Universitat Jaume I (project UJI-B2018-53 to V. M. A. and project UJI-A2020-21 to MQM). SV thanks Croatian Science Foundation (project IP-2018-01-3168). Catarina I.G. Pinto is enrolled in the PhD scholarship 689 DFA/BD/07119/2020. Publisher Copyright: © 2022 The Royal Society of Chemistry.