National Institute Of Materials Physics - Romania

Overexpression of pyruvate kinase (PyK) is linked to many kinds of malignant tumors, representing therefore one of the most promising therapeutic targets for cancer treatment. Inhibition of PyK slows down tumor growth or causes tumor cell death, minimizing cancer cell proliferation, and understanding inhibitor mechanism of action can significantly improve cancer therapy. The present work describes the use of an amperometric bienzymatic biosensor, based on PyK and pyruvate oxidase (PyOx), in enzyme inhibition studies of four kinase inhibitors, CPG77675, Nilotinib, Ruxolitinib, Cerdulatinib. Their inhibition mechanism is studied and discussed in detail, with a thorough evaluation of their enzyme-inhibitor complex binding constants (Ki) and the inhibitor concentration required for 50% inhibition (IC50), employing standard inhibition procedure graphical methods. The biosensor is successfully applied for the quantification of the inhibitors by fixed potential amperometry, with excellent detection limit values in the pM range. It is the first detection method reported for the anticancer drugs CPG77675 and Cerdulatinib. The electrochemical assay based on the biosensor brings several advantages over the available assay kits for high-throughput screening (HTS) of kinase inhibitors, namely: low cost, easy operability and robustness demonstrated by biosensor high reproducibility and both operational and storage stability, offering an opportunity to discover new inhibitors and optimize their therapeutic index.

We report the synthesis and characterization of folic acid (FA)-conjugated human serum albumin nanoparticles, (HSA-FA):Ru NPs, as targeted carriers for rutin (Ru), a flavonoid with known anticancer activity. Nanoparticles were fabricated via a desolvation method, and their surface was functionalized with folic acid to promote selective uptake by cancer cells overexpressing folate receptors. Morphological and dimensional analyses performed by atomic force microscopy (AFM), scanning electron microscopy (SEM), and fluorescence microscopy confirmed that all nanoparticles were below 100 nm and exhibited good colloidal stability. Voltametric measurements confirmed the successful incorporation of both rutin and folic acid within the (HSA-FA):Ru nanoparticle formulation. Biological evaluation was conducted on healthy L929 fibroblasts and HT-29 colon adenocarcinoma cells. MTS colorimetric assays revealed that (HSA-FA):Ru NPs significantly reduced the viability of HT-29 cells, while maintaining higher compatibility with L929 cells. Fluorescence and electron microscopy further confirmed preferential nanoparticle uptake and surface accumulation in HT-29 cells, supporting the role of folic acid in enhancing targeted delivery. The study demonstrates that HSA-based nanoparticles functionalized with FA and loaded with Ru offer a biocompatible and efficient strategy for selective intracellular drug delivery in colorectal cancer. These findings support the use of albumin-based nanocarriers in the development of targeted therapeutic platforms for cancer treatment.

Due to the importance of buffer layers in interface engineering, the development of more variants and the rational design of materials have a significant influence on the performance of optoelectronic devices. This study provides a strategy to increase device performance by facilitating efficient charge transfer and defect passivation by combining the properties of eco-friendly materials (adenine, cytosine, guanine, thymine, and uracil) with the physicochemical properties of metal oxides. The aim of this paper was to investigate the interaction of zinc oxide (ZnO) nanostructures (seed, nanoparticles, and nanowires) with nucleobase layers and to discuss their potential applications as organic-inorganic interfacial bilayers. The impact is analyzed from structural, morphological, optical, and electrical points of view. Nucleobase-ZnO nanostructure layers present high optical transparency in the visible range. Electrical measurements confirmed that the high surface area of nanowires can enhance interactions with nucleobases, leading to better charge transfer. The results showed that these nucleobase-ZnO nanostructure layers are promising interface materials for enhancing optoelectronic device performance through interfacial charge transport and light management, while enabling the design of environmentally friendly devices.

Paper-based devices hold great promise in biosensing, but the choice of electrode materials influences performance. Here, we report a paper-based electrochemical sensor developed for nucleic acid quantification, in a sandwich-type architecture integrating 3-electrode systems on metallized electrospun polymeric fibers. A 3D-printed hydrophobic barrier on the chromatographic paper defines injection and testing zones. Fluid diffusion through paper and concentration gradients are considered in the design. Electrochemical characterization is performed using 40 mu L of methylene blue solution, which interacts with double-stranded nucleic acids, reducing its redox activity. This interaction mechanism within the paper substrate is confirmed by spectroscopy. The sensor achieves detection of nucleic acids in 3 min with 2 mu L of solution. Real sample analysis is performed for the quantification of PCR-amplified genes with a limit of detection of 1.38 ng mu L-1. The device serves as a promising point-of-care diagnostics tool for the direct quantification of amplified genetic material.

We investigate the energy spectrum and transport properties of a diatomic square lattice model that manifest antichiral characteristics. The emergence of antichiral edge states is primarily governed by the relative sign of the next-nearest-neighbor hopping parameters on the two sublattices. However, in finite systems, the atomic structure at the boundaries plays a crucial role in determining whether the system exhibits chiral/antichiral behavior. Using both analytical and numerical methods, we reveal the presence of antichiral edge states in ribbon geometries and emphasize the importance of atomic connectivity at the edges. Extending our analysis, we simulate various finite size geometries to identify which configuration supports antichiral behavior. The transport properties are studied in the Landauer-B & uuml;ttiker approach for a Hall device with four leads. We study the transmittance coefficients, transverse (Hall), and longitudinal resistance by comparing the antichiral versus chiral situations. In particular, the antichiral case shows a vanishing Hall effect and negative longitudinal resistance. The presence of the bulk currents is proved by calculating explicitly the currents on the plaquette and the local density of states in the system with leads. Additionally, we investigate the influence of Anderson disorder on the transmittance coefficients to highlight the reduced robustness of antichiral systems.

This study describes the development of a pyruvate kinase (PyK)-biosensor for the evaluation of PyK activity, as a diagnostic tool for early cancer screening and detection of kinase inhibitors used in cancer treatment, with the evaluation of the inhibition mechanism. The biosensor was constructed by co-immobilizing the enzymes PyK and pyruvate oxidase (PyOx) on Au film electrodes by crosslinking with glutaraldehyde (GA) and evaluated electrochemically by cyclic voltammetry (CV) and fixed potential amperometry (CA). First, the experimental conditions were optimized in terms of applied potential, enzyme ratio PyK:PyOx and enzyme substrate concentration: phosphoenolpyruvate (PEP) and adenosine diphosphate (ADP). The biosensor sensitivity towards PEP detection was 2.11 +/- 0.08 mu A mM- 1 cm- 2, with very high reproducibility and repeatability, which made it suitable for inhibition studies of PyK inhibitor. The inhibition mechanism of shikonin was determined in relation to both PEP and ADP, with the calculation of IC50 values and binding constants (Ki). Detection of shikonin was possible at very low concentrations in the linear range of 0.1-4.0 pM. The electrochemical results were validated by UV-Vis spectrophotometry. The developed biosensor is a valuable tool for drug screening by enabling enzyme catalytic function examination with applicability to identify inhibitors, estimate their affinity, inhibition mechanism linked to their molecular mechanisms of action and evaluate selectivity, of great interest in both pharmaceutical and medical domains.

Bilayer metallic electrodes of magnesium and zinc-aluminum alloys Mg/Zn:Al were prepared using combined laser-thermionic vacuum arc methods. Plasma diagnosis suggests laser-plasma interaction by increasing the discharge voltage when the laser is on, which is converted by thermal annealing of plasma ions. A magnesium thin film with a lower work function, covered with a Zn:Al (4:1) layer was successfully used for efficient charge injection into electroluminescent diodes. The zinc-aluminum combination preserved the electrical conductivity of the thin magnesium film and protected it against oxidation. The capacitance-voltage measurements confirmed the integrity of the magnesium layer, whereas the work function was not affected. The zinc-aluminum alloy obtained through a thermionic vacuum arc exhibits good conductivity compared to pure zinc layers and better stability against degradation.

Understanding the behavior of biomaterials under physiological conditions is essential for the development of new materials for implants and bone regeneration. This study addresses the critical need to evaluate how exposure to simulated body fluid (SBF) affects hydroxyapatite (HAp) and dextran-coated hydroxyapatite (HApDx) nanoparticles, which are widely considered for biomedical applications due to their bioactivity and biocompatibility. Structural, morphological, and surface property changes induced by SBF immersion were systematically investigated for the first time using advanced characterization techniques, such as X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), FT-Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and fractal and Minkowski functional analyses. The results revealed that SBF immersion significantly influenced both HAp and HApDx, leading to reduced crystallite sizes, surface smoothening, and enhanced structural homogeneity. FTIR and FT-Raman spectra indicated subtle structural modifications, while SEM and AFM analyses confirmed the formation of a biomimetic apatite layer and a decrease in surface roughness. These changes are indicative of improved bioactivity, suggesting enhanced potential for osteoconductivity and cellular interaction. Biological evaluations using MG63 osteoblast-like cells demonstrated favorable cell viability and adhesion across 24, 48, and 72 h, particularly for the samples immersed in SBF. AFM further confirmed that surface modifications supported the cell attachment and proliferation. Overall, our findings underscore the importance of SBF exposure in enhancing the physicochemical and biological performance of HAp-based materials, reinforcing their promise for biomedical applications.

This study investigates the development of electrochemical genosensors using gold-coated electrospun polymeric fibers electrodes, Au/PMMA/PET and immobilized phosphorothioated oligonucleotides. Scanning electron microscopy (SEM) with energy-dispersive X-rays spectroscopy (EDS) revealed a uniform distribution of oligonucleotides on the fibers, contrary to planar gold electrodes Au/Ti/SiO2/Si, where network-like films were observed. X-ray photoelectron spectroscopy (XPS) confirmed the successful immobilization of the phosphorothioated oligonucleotides via strong covalent gold-sulfur bonds, while surface plasmon resonance (SPR) indicated superior binding affinity, with significantly lower equilibrium dissociation constants, when compared to unmodified probes. The detection of BCR/ABL fusion gene of chronic myeloid leukemia using differential pulse voltammetry and methylene blue as electroactive indicator, showed that the Au/PMMA/PET electrodes achieved a sensitivity of 379 +/- 12 mu A cm(-)(2) pM(-)(1) and a limit of detection of similar to 5.00 +/- 0.01 fM, outperforming the Au/Ti/SiO2/Si planar electrodes. Reduced non-specific adsorption was observed on the Au/PMMA/PET electrodes and attributed to the inherent charges introduced during the electrospinning process, which created localized electrostatic fields that repelled weakly adsorbing molecules. These findings demonstrate the potential of Au/PMMA/PET electrodes as a robust platform for further development of high-performance clinical diagnostic devices.

Understanding the behavior of biomaterials under physiological conditions is essential for the development of new materials for implants and bone regeneration. This study addresses the critical need to evaluate how exposure to simulated body fluid (SBF) affects hydroxyapatite (HAp) and dextran-coated hydroxyapatite (HApDx) nanoparticles, which are widely considered for biomedical applications due to their bioactivity and biocompatibility. Structural, morphological, and surface property changes induced by SBF immersion were systematically investigated for the first time using advanced characterization techniques, such as X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), FT-Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and fractal and Minkowski functional analyses. The results revealed that SBF immersion significantly influenced both HAp and HApDx, leading to reduced crystallite sizes, surface smoothening, and enhanced structural homogeneity. FTIR and FT-Raman spectra indicated subtle structural modifications, while SEM and AFM analyses confirmed the formation of a biomimetic apatite layer and a decrease in surface roughness. These changes are indicative of improved bioactivity, suggesting enhanced potential for osteoconductivity and cellular interaction. Biological evaluations using MG63 osteoblast-like cells demonstrated favorable cell viability and adhesion across 24, 48, and 72 h, particularly for the samples immersed in SBF. AFM further confirmed that surface modifications supported the cell attachment and proliferation. Overall, our findings underscore the importance of SBF exposure in enhancing the physicochemical and biological performance of HAp-based materials, reinforcing their promise for biomedical applications.