Nanomedicines inability to penetrate throughout the entire tumor volume due to heterogeneous distribution within the tumor mass remains a crucial limiting factor for a vast range of theranostic applications, including image-guided radiation therapy. Despite innumerable studies conducted on the topic have shown efficacy and biocompatibility of colloidal gold nanoparticles (GNPs), the biological effects of GNPs in the tumor microenvironment, including the particle-protein interaction and the consequent impact on cellular pathways and contrast enhancement remain unclear. In this regard, further investigations on how GNP surface passivation effects X-ray attenuation as well as in vivo biodistribution will clarify several aspects still under discussion from the scientific community, which so far have limited the clinical translation of their applications cancer-related.

We aim to evaluate the influence of protein surface adsorption on the GNP biodistribution in Lewis Lung Carcinoma (LLC) tumor-bearing mice using high resolution Computed Tomography (CT) preclinical imaging. We hypothesize that by controlling the adsorption of proteins on the GNP surface, we can influence the intratumoral distribution and retention of the particles.

GNPs approximately 34 nm in diameter are synthesized with a surface plasmon peak at ~530 nm, surface passivated with Bovine Serum Albumin (BSA) to reduce opsonization and improve colloidal stability, and characterized with standard methods. Modulation of BSA adsorption on the GNPs is observed by tuning the pH of the immobilization medium from acidic to alkaline, which we quantify using Langmuir isotherms. CT phantom imaging is used to determine X-ray attenuation as a function of GNP concentration and surface functionalization. The in vitro study for evaluating the uptake of GNPs by Lewis Lung Carcinoma cells highlighted a difference in the internalization depending on the surface functionalization. In both cases, macropinocytosis is the trafficking mechanism, but while endosomes with citrate-GNPs can be found in different stages of maturation, cells treated with BSA-GNPs presented larger vesicles up to 1μm in diameter. The in vivo study is performed by injecting intratumorally, concentrated GNPs into Lewis Lung Carcinoma (LLC) solid tumors grown on the right flank of 6-week old female C57BL/6 mice. Ten days post-injection, follow-up assessments with CT imaging show the distribution and retention of the particles in the tumor. CT attenuation quantification based on bioimaging analysis for each time point is conducted.

In vivo results show significant heterogeneity in the intratumoral biodistribution of GNPs dependent on surface passivation. BSA-GNPs perfuse predominately along the tumor periphery with few depositions throughout the entire tumor volume. This response can be explained by the abnormal and heterogeneous vascular structure of the LLC tumor, suggesting perfusion rather than permeability as the limiting factor for tumor accumulation of the GNPs. Despite the perivascular cluster accumulation, the BSA-GNP distribution diverges from that obtained after unpassivated, citrate-GNP intratumoral injections.

In conclusion, our investigations have shown that surface passivation of GNPs is able to influence the mechanism of cellular uptake in vitro and their in vivo intratumoral diffusion highlighting the spatial heterogeneity of the solid tumor.

Molybdenum blue are oxygen-containing compounds of molybdenum of variable composition in which molybdenum is in oxidation states + 5 and + 6. Molybdenum-oxygen clusters represent a large class of polyoxometalates. Under certain conditions, it is possible to synthesize clusters of a certain shape and size. The nanosized of the clusters and their monodispersity make it possible to consider molybdenum blue as promising precursors for the synthesis of various catalysts, especially for preparation of refractory compounds - molybdenum carbides or nitrides.

For the synthesis of supported catalysts using dispersions of nanoparticles (sols), it is necessary to know their main colloidal-chemical properties, the most important of which are electro-surface characteristics, rheological properties and the conditions for maintaining aggregative stability.

The paper presents the results of a study of the colloidal-chemical properties of molybdenum blue, the dispersed phase of which is represented by toroidal particles of the class Mo₁₅₄-x. It was found that aggregate stable dispersions exist in the pH range from 0.8 to 3.0 pH units. In the investigated pH range, molybdenum blue particles are negatively charged, and the electrokinetic potential does not exceed 30 mV. Molybdenum blues have high aggregate stability and can be concentrated to a high concentration of the dispersed phase (20-30 wt%); at higher concentrations, a transition of the sol into a gel is observed. In a wide range of concentrations molybdenum blues are Newtonian liquids, the viscosity of which mainly depends on the concentration of the dispersed phase. It was found that dispersions are characterized by the presence of electro-viscous effects. The nature of the aggregate stability of the dispersions of molybdenum blue is discussed.

Lately, the optical properties of Graphene Oxide (GO) and Reduced Graphene Oxide (RGO) films have been studied in the ultraviolet and visible spectral range. However, the accurate optical properties in the extended near-infrared and mid-infrared range have not been published yet. In this work, we report a Variable Angle Spectroscopic Ellipsometry (VASE) characterization of GO thin films dip-coated on SiO₂/Si substrates and thermally reduced GO films in the [0.38-4.1] eV photon energy range. Moreover, the optical properties of RGO stabilized with poly(sodium 4-styrenesulfonate) (PSS) films dip-coated on SiO₂/Si substrates are studied in the same range for the first time. The Lorentz optical models fit well the experimental data. In addition, the morphological properties of the samples were investigated by Scanning Electron Microscopy (SEM) analysis.

In this research, photocatalysts based on TiO₂ modified by fluorination and platinum addition were evaluated in the glycerol oxidation. These materials were characterized by different instrumental analysis techniques to determine the physicochemical properties. It was found that the surface modification lead to improve the materials absorption in the Visible region of the electromagnetic spectra and to increase the surface area of TiO₂. By HPLC analysis was possible to observed that the photocatalysts 0.5% Pt-F-TiO₂ showed the highest yield and selectivity towards glyceraldehyde (GAL). It was also observed that the increase in the platinum content until values of 2% had a negative effect in the effectiveness of fluorinated Titania in the glycerol photo-oxidation. The fluorination and platinum addition modify some physicochemical properties of TiO₂, leading also to modify the reaction mechanism and selectivity during glycerol partial photo-oxidation and the dose of photocatalysts is an important reaction condition to obtain GAL and Dyhidroxyacetone (DHA) with yields above to 70%.

Nanogels are a novel class of three-dimensional cross-linked polymers able to retain high amounts of water in their network structure, with large potential applications in nanomedicine. In our study, the polymer matrix selected was chitosan, as this polysaccharide biopolymer composed of N-acetylglucosamine and glucosamine residues exhibit great biocompatibility and low toxicity. The preparation was performed by ionic gelation in the presence of hyaluronic acid and sodium tripolyphosphate, having rhodamine or fluorescein isothiocyanate molecules grafted on chitosan backbone. In order to validate the possible usage of these chitosan-fluorophores conjugates for fluorescence imaging purposes in cancer diagnostics and therapy, their biological effect was assessed on SVEC4-10 cells (a simian virus 40-transformed mouse microvascular endothelial cell line). Cell viability, membrane integrity and nanogels uptake were examined following the exposure for 6 and 24 hours at concentrations up to 120 µg/mL. A good biocompatibility was obtained after both time intervals of incubation with nanogels, as no increase in cell death or membrane damage being noticed compared to control. By examination on confocal laser scanning microscopy, the both types of fluorescent nanogels agglomerated on the surface of cell membrane, their cellular internalization being observed only for few cells, preferentially at the cell periphery. In conclusion, based on the biocompatibility of the nanogels, these can further incorporate gadolinium for an improved magnetic resonance Imaging effect in nanomedicine.

Acknowledgments This work was supported by a grant of the Romanian Ministry of Research and Innovation, CCCDI - UEFISCDI, project number PN-III-P3-3.1-PM-RO-FR-2019-0204 / 6 BM/ 2019, within PNCDI III.