Development of Fe3O4 core-TiO2 shell nanocomposites and nanoconjugates as a foundation for neuroblastoma radiosensitization.

BACKGROUND: Neuroblastoma is the most common extracranial solid malignancy in childhood which, despite the current progress in radiotherapy and chemotherapy protocols, still has a high mortality rate in high risk tumors. Nanomedicine offers exciting and unexploited opportunities to overcome the shortcomings of conventional medicine. The photocatalytic properties of Fe3O4 core-TiO2 shell nanocomposites and their potential for cell specific targeting suggest that nanoconstructs produced using Fe3O4 core-TiO2 shell nanocomposites could be used to enhance radiation effects in neuroblastoma. In this study, we evaluated bare, metaiodobenzylguanidine (MIBG) and 3,4-Dihydroxyphenylacetic acid (DOPAC) coated Fe3O4@TiO2 as potential radiosensitizers for neuroblastoma in vitro. RESULTS: The uptake of bare and MIBG coated nanocomposites modestly sensitized neuroblastoma cells to ionizing radiation. Conversely, cells exposed to DOPAC coated nanocomposites exhibited a five-fold enhanced sensitivity to radiation, increased numbers of radiation induced DNA double-strand breaks, and apoptotic cell death. The addition of a peptide mimic of the epidermal growth factor (EGF) to nanoconjugates coated with MIBG altered their intracellular distribution. Cryo X-ray fluorescence microscopy tomography of frozen hydrated cells treated with these nanoconjugates revealed cytoplasmic as well as nuclear distribution of the nanoconstructs. CONCLUSIONS: The intracellular distribution pattern of different nanoconjugates used in this study was different for different nanoconjugate surface molecules. Cells exposed to DOPAC covered nanoconjugates showed the smallest nanoconjugate uptake, with the most prominent pattern of large intracellular aggregates. Interestingly, cells treated with this nanoconjugate also showed the most pronounced radiosensitization effect in combination with the external beam x-ray irradiation. Further studies are necessary to evaluate mechanistic basis for this increased radiosensitization effect. Preliminary studies with the nanoparticles carrying an EGF mimicking peptide showed that this approach to targeting could perhaps be combined with a different approach to radiosensitization - use of nanoconjugates in combination with the radioactive iodine. Much additional work will be necessary in order to evaluate possible benefits of targeted nanoconjugates carrying radionuclides. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12645-021-00081-z.

Thermal source Fourier transform infrared microtomography applied to Arctic sea ice diatoms.

We have used thermal source Fourier Transform Infrared (FTIR) microtomographic imaging to compare sea ice diatoms growing under different light conditions. A prototype tomography accessory was designed to have sufficient degrees of freedom to align any tilted cylindrical sample relative to the axis of rotation, minimizing the off-axis path traced during rotation. The lightweight device rests on the motorized stage to position the sample in the field-of-view and enable mosaic imaging. Reconstruction routines were tested with simulated and real phantoms, to assess limitations in the Radon back-projection method employed. The distribution and abundance of biochemicals is analysed for targets larger than a single FPA tile. Two and three dimensional (2D and 3D) FTIR spectrochemical images were obtained with a Focal Plane Array (FPA, nominal 1.1 µm pixel edges) for phantoms (polystyrene beads in polyvinyl alcohol matrix) and diatom cells harvested from land fast, first-year ice sites in Resolute Passage (74 43.628'N; 95 33.330'W) and Dease Strait (69° 1.11'N; 105° 21.29'W), Nunavut, Canada. The analysis of relative concentrations of organic matter within the encapsulating silica frustules of diatoms is important for a better understanding of both the physiological state and the individual cellular response to environmental pressures. Analysis of 3D FTIR images of Nitzschia frigida collected from beneath high (17-19 cm) and low (3-7 cm) snow depth revealed higher concentrations of lipids in diatoms collected under low snow cover, uniquely based on spectroscopically determined total 3D cell volume and biochemical content.

Synchrotron-Based Three-Dimensional Fourier-Transform Infrared Spectro-Microtomography of Murchison Meteorite Grain.

We demonstrate nondestructive, three-dimensional, microscopic, infrared (IR) spectral in-situ imaging of an extraterrestrial sample. Spatially resolved chemical composition and spatial correlations are investigated within a single 45 µm grain of the Murchison meteorite. Qualitative and quantitative investigation through this analytical technique can help elucidate the origin and evolution of meteoritic compounds as well as parent body processes without damaging or altering the investigated samples.

Multifunctional supramolecular polymer networks as next-generation consolidants for archaeological wood conservation.

The preservation of our cultural heritage is of great importance to future generations. Despite this, significant problems have arisen with the conservation of waterlogged wooden artifacts. Three major issues facing conservators are structural instability on drying, biological degradation, and chemical degradation on account of Fe(3+)-catalyzed production of sulfuric and oxalic acid in the waterlogged timbers. Currently, no conservation treatment exists that effectively addresses all three issues simultaneously. A new conservation treatment is reported here based on a supramolecular polymer network constructed from natural polymers with dynamic cross-linking formed by a combination of both host-guest complexation and a strong siderophore pendant from a polymer backbone. Consequently, the proposed consolidant has the ability to chelate and trap iron while enhancing structural stability. The incorporation of antibacterial moieties through a dynamic covalent linkage into the network provides the material with improved biological resistance. Exploiting an environmentally compatible natural material with completely reversible chemistries is a safer, greener alternative to current strategies and may extend the lifetime of many culturally relevant waterlogged artifacts around the world.

SR-FTIR imaging of the altered cadmium sulfide yellow paints in Henri Matisse's Le Bonheur de vivre (1905-6)--examination of visually distinct degradation regions.

SR-FTIR imaging has been used to map the mid-IR active photo-degradation phases in two thin sections of cadmium yellow paint removed from Henri Matisse's Le Bonheur de vivre (1905-1906, The Barnes Foundation). These samples represent both the darkened cadmium yellow foliage in the upper left of the work and the lightened cadmium yellow field beneath the central reclining figures. The altered cadmium yellow paints from both regions were found to contain cadmium carbonate (CdCO3), cadmium sulphate (CdSO4), and cadmium oxalate (CdC2O4). Each of these phases was imaged to determine their positions as a function of depth, with the aim of better understanding the role of each phase in the degradation mechanism. This speciation mapping is critical because cadmium oxalate was used in this period as an additive in cadmium yellow light. In addition, cadmium carbonate and cadmium sulphate were synthesis starting materials for cadmium yellow, and so their distribution throughout the paint layer can provide an indication of their roles. It was established that cadmium oxalate is localized at the surface of the paint layer, cadmium carbonate is found deeper in the layer but still enriched at the surface, and cadmium sulphate is distributed throughout the layer. This distribution, along with the chloride content of the paint suggesting a cadmium chloride starting material, is consistent with an alteration mechanism in which the cadmium sulphide is oxidized to sulphate and this is then converted to carbonate and oxalate. The relative solubilities of the three photo-degradation products are also relevant to their locations in the paint film.

3D spectral imaging with synchrotron Fourier transform infrared spectro-microtomography.

We report Fourier transform infrared spectro-microtomography, a nondestructive three-dimensional imaging approach that reveals the distribution of distinctive chemical compositions throughout an intact biological or materials sample. The method combines mid-infrared absorption contrast with computed tomographic data acquisition and reconstruction to enhance chemical and morphological localization by determining a complete infrared spectrum for every voxel (millions of spectra determined per sample).

Imaging of vascular smooth muscle cells with soft X-ray spectromicroscopy.

Using X-ray microscopy and spectromicroscopy, vascular smooth muscle cells (VSMCs) were imaged, prepared without using additional embedding material or staining, but by applying simple, noncryo fixation techniques. The cells were imaged with a compact source transmission X-ray microscope and a scanning transmission X-ray microscope (STXM). With the STXM, spectromicroscopy was performed at the C K-edge and the Ca L(III,II)-edges. VSMCs were chosen because of their high amount of actin stress fibers, so that the actin cytoskeleton should be visible. Other parts of the cell, such as the nucleus and organelles, were also identified from the micrographs. Both in the spectra and the images, the effects of the different preparation procedures were observable. Furthermore, Ca hotspots were detected and their density is determined.

B-S transition in short oligonucleotides.

Stretching experiments with long double-stranded DNA molecules in physiological ambient revealed a force-induced transition at a force of 65 pN. During this transition between B-DNA and highly overstretched S-DNA the DNA lengthens by a factor of 1.7 of its B-form contour length. Here, we report the occurrence of this so-called B-S transition in short duplexes consisting of 30 basepairs. We employed atomic-force-microscope-based single molecule force spectroscopy to explore the unbinding mechanism of two short duplexes containing 30 or 20 basepairs by pulling at the opposite 5' termini. For a 30-basepair-long DNA duplex the B-S transition is expected to cause a length increase of 6.3 nm and should therefore be detectable. Indeed 30% of the measured force-extension curves exhibit a region of constant force (plateau) at 65 pN, which corresponds to the B-S transition. The observed plateaus show a length between 3 and 7 nm. This plateau length distribution indicates that the dissociation of a 30-basepair duplex mainly occurs during the B-S transition. In contrast, the measured force-extension curves for a 20-basepair DNA duplex exhibited rupture forces below 65 pN and did not show any evidence of a B-S transition.