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

Abstract

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. 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 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.

Water soluble organometallic small molecules as promising antibacterial agents: synthesis, physical–chemical properties and biological evaluation to tackle bacterial infections

“…The Na[ 1 ] cytotoxicity was tested on U87 and T98G glioblastoma cells, A375 melanoma cells and non-tumoral V79 fibroblasts, 16 and the cytotoxicity of Na[ 3 ] was tested against U87 and T98G glioblastoma cells. 44 The IC 50 (compound concentration causing 50% inhibition of cell growth) is a parameter used to evaluate the cytotoxicity of a given compound. The IC 50 values at 24 h of incubation time with Na[ 1 ] and/or Na[ 3 ] ranged from 59 μM to 195 μM, displaying no relevant cytotoxic activity, whereas the MIC values for the microorganisms tested here ranged from 0.002 μM to 0.653 μM.…”

“…and T98G glioblastoma cells. 44 The IC 50 (compound concentration causing 50% inhibition of cell growth) is a parameter used to evaluate the cytotoxicity of a given compound. The IC 50 values at 24 h of incubation time with Na[1] and/or Na [3] ranged from 59 µM to 195 µM, displaying no relevant cytotoxic activity, whereas the MIC values for the microorganisms tested here ranged from 0.002 µM to 0.653 µM.…”

Tuning the Biological Activity of Camphorimine Complexes through Metal Selection

“…The nematode strain, obtained from the Caenorhabditis Genetic Center, was maintained at 20 °C on Nematode Growth Medium (NGM) agar plates seeded with Escherichia coli OP50 under standard conditions and synchronized using standard protocols and as previously described [ 52 , 53 , 54 ]. L4 synchronized worms, prepared as previously described [ 53 , 54 ], were exposed to [Ag(NO 3 )( 1 A) 2 ] ( 5 ) complex final concentrations of 0, 1, 2.5, 5, 10, 25, 50, 100, 250, and 500 µM in M9 buffer (22.04 mM KH 2 PO 4 , 42.27 mM Na 2 HPO 4 , 85.56 mM NaCl, and 1 mM MgSO 4 ) supplemented with 0.2% ( w / v ) of dead E. coli OP50, for 96 h at 20 °C, in a final volume of 500 μL (24 wells) [ 55 ]. The total number of living and dead worms per well was assessed at 24, 48, 72, and 96 h timepoints with the aid of a Zeiss Stemi 2000-C stereomicroscope.…”

Importance of radiobiological studies for the advancement of boron neutron capture therapy (BNCT)

“…Refs27, 28) and bimodal drugs (with anti-tumoural and BNCT effects) such as metallocarboranes (e.g. Refs29, 30). As an example, icosahedral boron clusters have shown the relevance of these compounds as exquisite frameworks in the design of novel drug candidates (Refs31–33).…”