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 Na[3,3’-Fe(8-I-1,2-C2B9H10)2] and Na[2,2’-M(1,2-C2B9H11)] (M= Co3+, Fe3+), small molecules are synthesized and the X-ray structures [(H3O)(H2O)5][2,2’-Co(1,7-C2B9H11)2] and [Cs(MeCN)[8,8’-I2-Fe(1,2 C2B9H10)2], both displaying transoid conformation of [M(C2B9)2]- framework, are reported. Importantly, the...
There is an increasing interest in synthetic systems that can execute bio-inspired chemical reactions without requiring the complex structures that characterize enzymes in their components.The hierarchical self-assembly of peptides provides a means to create catalytic microenvironments. Ideally, as it occurs in enzymes, the catalytic activity of peptide nanostructures should be reversibly regulated. In a typical enzyme mimetic design, the peptide's self-assembling and catalytic activities are segregated into different regions of the sequence. Here, we aimed to design minimal peptides in which the self-assembly and function were all encoded in the same amino acids. Moreover, we wanted to endorse the resulting one-component nanomaterial with divergent, chemically unrelated, catalytic activities, a property not observed in natural enzymes. We show that short peptides consisting only of histidine and tyrosine residues, arranged in a binary pattern, form biocompatible amyloid-like fibrils and hydrogels combining hydrolytic and electrocatalytic activities. The nanofibers' mesoscopic properties are controlled by pH, the transition between assembled active b-sheet fibrils, and disassembled inactive random coil species occurring in a physiologically relevant pH range. The structure of one of such amyloid-like fibrils, as derived from molecular dynamic simulations, provides insights on how they attain this unique combination of structural and catalytic properties.
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.
Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, highly resistant to conventional radiotherapy and chemotherapy. Therefore, the development of multidrug resistance and tumor recurrence are frequent....
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.
Here, we dope an electroactive reversible redox polymer PEDOT with a reversible redox active metallacarborane having tunable potential to generate a synergistic material with superior properties such as a low overpotential to generate O2 from water.
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