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.

The anionic cobaltabis (dicarbollide) [3,3′-Co(1,2-C₂B₉H₁₁)₂]⁻, [o-COSAN]⁻, is the most studied icosahedral metallacarborane. The sodium salts of [o-COSAN]⁻ could be an ideal candidate for the anti-cancer treatment Boron Neutron Capture Therapy (BNCT) as it possesses the ability to readily cross biological membranes thereby producing cell cycle arrest in cancer cells. BNCT is a cancer therapy based on the potential of ¹⁰B atoms to produce α particles that cross tissues in which the ¹⁰B is accumulated without damaging the surrounding healthy tissues, after being irradiated with low energy thermal neutrons. Since Na[o-COSAN] displays a strong and characteristic ν(B-H) frequency in the infrared range 2.600–2.500 cm⁻¹, we studied the uptake of Na[o-COSAN] followed by its interaction with biomolecules and its cellular biodistribution in two different glioma initiating cells (GICs), mesenchymal and proneural respectively, by using Synchrotron Radiation-Fourier Transform Infrared (FTIR) micro-spectroscopy (SR-FTIRM) facilities at the MIRAS Beamline of ALBA synchrotron light source. The spectroscopic data analysis from the bands in the regions of DNA, proteins, and lipids permitted to suggest that after its cellular uptake, Na[o-COSAN] strongly interacts with DNA strings, modifies proteins secondary structure and also leads to lipid saturation. The mapping suggests the nuclear localization of [o-COSAN]⁻, which according to reported Monte Carlo simulations may result in a more efficient cell-killing effect compared to that in a uniform distribution within the entire cell. In conclusion, we show pieces of evidence that at low doses, [o-COSAN]⁻ translocates GIC cells’ membranes and it alters the physiology of the cells, suggesting that Na[o-COSAN] is a promising agent to BNCT for glioblastoma cells.

Background: Boron neutron capture therapy (BNCT) is a tumor-selective particle radiotherapy that combines preferential boron accumulation in tumors and neutron irradiation. Based on previous studies in tumor-bearing mice, this study evaluated the biodistribution of the sodium salt of cobaltabis(dicarbollide) (Na[3,3′-Co(C₂B₉H₁₁)₂], abbreviated as Na[o-COSAN]) in the hamster cheek pouch oral cancer model and the Na[o-COSAN]/BNCT therapeutic effect on tumors and induced radiotoxicity. The synthesis and comprehensive characterization of ¹⁰B-enriched trimethylammonium salt of nido-[7,8-C₂¹⁰B₉H₁₂]⁻o-carborane, along with the cesium and sodium salts of [o-¹⁰COSAN] cobaltabis(dicarbollide) are reported here for the first time. Methods: Hamsters bearing tumors were injected with Na[o-COSAN] (7.5 mg B/kg) and euthanized at different time-points after injection (30 min, 2, 3, 5, and 18 h post-administration) to evaluate boron uptake in different tissues/organs. Based on these results, tumor-bearing animals were treated with Na[¹⁰B-o-COSAN]/BNCT (7.5 mg B/kg b.w., 3 h), prescribing 5 Gy total in absorbed dose to the precancerous tissue surrounding tumors, i.e., the dose-limiting tissue. Results: Na[o-¹⁰COSAN] exhibited no toxicity. Although biodistribution studies employing Na[o-COSAN] have shown low absolute boron concentration in the tumor (approx. 11 ppm), Na[o-¹⁰COSAN]/BNCT induced a high and significant therapeutic effect on tumors versus the control group (cancerized, untreated animals). Moreover, only half of the animals exhibited severe mucositis in the precancerous dose-limiting tissue after BNCT, which resolved completely at 21 days after irradiation. Conclusions: Na[o-¹⁰COSAN] would be potentially useful to treat head and neck cancer with BNCT.

In this paper, we investigated how different growth conditions (i.e., temperature, growth time, and composition) allows for trading off cost (i.e., In content) and performance of nanostructured indium tin oxide (ITO) for biosensing applications. Next, we compared the behavior of these functionalized nanostructured surfaces obtained in different growth conditions between each other and with a standard thin film as a reference, observing improvements in effective detection area up to two orders of magnitude. This enhanced the biosensor’s sensitivity, with higher detection level, better accuracy and higher reproducibility. Results show that below 150 °C, the growth of ITO over the substrate forms a homogenous layer without any kind of nanostructuration. In contrast, at temperatures higher than 150 °C, a two-phase temperature-dependent growth was observed. We concluded that (i) nanowire length grows exponentially with temperature (activation energy 356 meV) and leads to optimal conditions in terms of both electroactive surface area and sensitivity at around 300 °C, (ii) longer times of growth than 30 min lead to larger active areas and (iii) the In content in a nanostructured film can be reduced by 10%, obtaining performances equivalent to those found in commercial flat-film ITO electrodes. In summary, this work shows how to produce appropriate materials with optimized cost and performances for different applications in biosensing.

Two distinctive types of protein interactions modelled on the basis of basic amino acid residues on the protein surface using the anionic ‘small molecule’ probe [o-COSAN]⁻.

Background: Radiosensitizers can be used to enhance tumor response and mitigate toxicity in healthy tissues during radiation therapy. This study investigates the radiosensitizing potential of the metallacarborane Fe/⁵⁷Fe-ferrabisdicarbollide in SK-BR-3 and MDA-MB-231 breast cancer cells, using two distinct gamma-photon sources: high-dose ⁶⁰Co (2.08 Gy) and low-dose ⁵⁷Co (37.55 mGy, ⁵⁷Fe Mössbauer effect). Methods: We evaluated cell viability and survival in 2D monolayer and 3D spheroid cultures, as well as the mechanism of cell death (ROS production, apoptosis or necrosis). Computational dosimetry was used to calculate the average absorbed dose. Results: In 2D models, both radiation sources induced reduced viability and increased ROS, with distinct cell death patterns dependent on the source (apoptosis or necrosis). Comparing 2D and 3D MDA-MB-231 models revealed that spheroid survival was significantly more impaired. The low-dose ⁵⁷Co source caused a significant radiosensitization in MDA-MB-231 spheroids, dramatically impacting viability and survival. This effect is attributed to the Mössbauer effect, where the resonant absorption of 14.41 keV radiation by ⁵⁷Fe leads to a massive, localized dose enhancement. The subsequent cascade of Auger and conversion electrons (local high LET) caused significantly greater cellular damage than sparse photon radiation. Conclusions: Fe/⁵⁷Fe-ferrabisdicarbollide demonstrates a potent radiosensitizing effect depending on the cell model and the radiation source used. Crucially, the observed radiosensitization allows for the development of a new, more efficient cancer radiotherapy approach that can achieve therapeutic efficacy using a significantly lower radiation dose to the patient. This paves the way for safer and better-tolerated cancer treatments.