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

钴胺素(二碳酰胺)([ o-COSAN]-)作为多功能化疗药物:在胶质母细胞瘤硼中子俘获疗法 (BNCT) 中的预期应用

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作者:Miquel Nuez-Martinez, Catarina I G Pinto, Joana F Guerreiro, Filipa Mendes, Fernanda Marques, Amanda Muñoz-Juan, Jewel Ann Maria Xavier, Anna Laromaine, Valeria Bitonto, Nicoletta Protti, Simonetta Geninatti Crich, Francesc Teixidor, Clara Viñas

Conclusions

These small molecules, particularly [8,8'-I2-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.

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.

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'-I2-o-COSAN]) could be promising agents for dual anti-cancer treatment (chemotherapy + BNCT) for GBM.

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 10B inside the cells is enough for BNCT irradiation. BNCT becomes more effective on T98G after their incubation with Na[8,8'-I2-o-COSAN], whereas no apparent cell-killing effect was observed for untreated cells. Conclusions: These small molecules, particularly [8,8'-I2-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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