4.6 Article

Cobaltabis(dicarbollide) ([o-COSAN]-) as Multifunctional Chemotherapeutics: A Prospective Application in Boron Neutron Capture Therapy (BNCT) for Glioblastoma

期刊

CANCERS
卷 13, 期 24, 页码 -

出版社

MDPI
DOI: 10.3390/cancers13246367

关键词

boron clusters; metallacarboranes; small molecules; COSAN; boron neutron capture therapy (BNCT); glioblastoma; 3D cell models; in vitro BNCT effect; C; elegans

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资金

  1. Spanish Ministerio de Economia y Competitividad [PID2019-106832RB-I00, RTI2018-096273-B-I00]
  2. Generalitat de Catalunya [2017SGR1720, 2017SGR765]
  3. 'Severo Ochoa' Program for Centers of Excellence in RD [SEV-2015-0496]
  4. AIRC (Associazione Italiana per la Ricerca sul Cancro) [23267]
  5. Fundacao para a Ciencia e Tecnologia (FCT) Portugal [UID/MULTI/04349/2019, PTDC/BTM-TEC/29256/2017, DFA/BD/07119/2020]
  6. DOC-FAM program under the Marie Sklodowska-Curie grant [754397]
  7. UAB [FPU18/05190]
  8. EPNOE [RED2018-102469-T]
  9. Fundação para a Ciência e a Tecnologia [PTDC/BTM-TEC/29256/2017] Funding Source: FCT

向作者/读者索取更多资源

The study evaluates the potential of sodium salt of cobaltabis(dicarbollide) and its di-iodinated derivative as promising agents for dual anti-cancer treatment for GBM. Results show enhanced resistance in U87 cell lines in 3D models, contrasting the observations in monolayer cultures. BNCT is more effective on T98G cells after their incubation with Na[8,8 '-I-2-o-COSAN].
Simple Summary Glioblastoma multiforme (GBM) is one of the most common malignant brain tumors. Although a variety of GBMs is initially susceptible to chemotherapy, the development of multi-drug resistance and recurrence is frequent. Therefore, there is an urgent need for more efficient treatment modalities for GBM. Boron neutron capture therapy (BNCT) is a cancer therapy based on the potential of B-10 atoms to produce alpha particles that cross tissues in which the B-10 accumulates without damaging the surrounding healthy tissues after irradiation with low energy thermal neutrons. The aim of our study was to assess that the sodium salt of cobaltabis(dicarbollide) and its di-iodinated derivative could be good candidates for dual anti-cancer treatment (chemotherapy + BNCT). Our results strongly suggest that these small molecules, in particular [8,8 '-I-2-o-COSAN](-), are serious candidates to be taken into account for BNCT now that the accelerator-based neutron source facilities are more accessible, providing an alternative treatment for resistant glioblastoma. Purpose: The aim of our study was to assess if the sodium salt of cobaltabis(dicarbollide) and its di-iodinated derivative (Na[o-COSAN] and Na[8,8 '-I-2-o-COSAN]) could be promising agents for dual anti-cancer treatment (chemotherapy + BNCT) for GBM. Methods: The biological activities of the small molecules were evaluated in vitro with glioblastoma cells lines U87 and T98G in 2D and 3D cell models and in vivo in the small model animal Caenorhabditis elegans (C. elegans) at the L4-stage and using the eggs. Results: Our studies indicated that only spheroids from the U87 cell line have impaired growth after treatment with both compounds, suggesting an increased resistance from T98G spheroids, contrary to what was observed in the monolayer culture, which highlights the need to employ 3D models for future GBM studies. In vitro tests in U87 and T98G cells conclude that the amount of B-10 inside the cells is enough for BNCT irradiation. BNCT becomes more effective on T98G after their incubation with Na[8,8 '-I-2-o-COSAN], whereas no apparent cell-killing effect was observed for untreated cells. Conclusions: These small molecules, particularly [8,8 '-I-2-o-COSAN](-), are serious candidates for BNCT now that the facilities of accelerator-based neutron sources are more accessible, providing an alternative treatment for resistant glioblastoma.

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