Dániel Madarász

Silver nanoparticles defeat p53-positive and p53-negative osteosarcoma cells by triggering mitochondrial stress and apoptosis

Loss of function of the tumour suppressor p53 observed frequently in human cancers challenges the drug-induced apoptotic elimination of cancer cells from the body. This phenomenon is a major concern and provides much of the impetus for current attempts to develop a new generation of anticancer drugs capable of provoking apoptosis in a p53-independent manner. Since silver nanoparticles (AgNPs) possess unique cytotoxic features, we examined, whether their activity could be exploited to kill tumour suppressor-deficient cancer cells. Therefore, we investigated the effects of AgNPs on osteosarcoma cells of different p53 genetic backgrounds. As particle diameters might influence the molecular mechanisms leading to AgNP-induced cell death we applied 5 nm and 35 nm sized citrate-coated AgNPs. We found that both sized AgNPs targeted mitochondria and induced apoptosis in wild-type p53-containing U2Os and p53-deficient Saos-2 cells. According to our findings AgNPs are able to kill osteosarcoma cells independently from their actual p53 status and induce p53-independent cancer cell apoptosis. This feature renders AgNPs attractive candidates for novel chemotherapeutic approaches.

Silver nanoparticles modulate ABC transporter activity and enhance chemotherapy in multidrug resistant cancer.

UNLABELLED The emergence of multidrug resistant (MDR) cancer phenotypes dramatically attenuates the efficiency of antineoplastic drug treatments often leading to the failure of chemotherapy. Therefore there is an urgent need to engineer new therapeutically useful agents and propose innovative approaches able to defeat resistant cancer cells. Although the remarkable anti-cancer features of silver nanoparticles (AgNPs) have already been delineated their impact on MDR cancer has never been investigated. Herein, we report that AgNPs have notable anti-proliferative effect and induce apoptosis mediated cell death both in drug sensitive and in MDR cancer cells. Furthermore we show evidence that AgNPs exert an inhibitory action on the efflux activity of MDR cancer cells which feature could be exploited to enhance drug accumulation. We verified synergistic interactions of AgNPs with six different antineoplastic agents on drug resistant cells which emphasizes the excellent potential of AgNPs as combinational partners in the chemotherapy of MDR cancer. FROM THE CLINICAL EDITOR The treatment of cancer often fails due to the development of multidrug resistant (MDR) cancer cells. Hence, novel approaches are being investigated to combat drug resistant cancer cells. One particular method studied here uses silver nanoparticles (AgNPs). The authors showed that AgNPs had anti-proliferative effect and ?exerted an inhibitory action on ABC transporter. The findings could suggest the possible use of AgNPs in combination with other chemotherapeutic agents in the clinical setting.

Metal loading determines the stabilization pathway for Co2+ in titanate nanowires: ion exchange vs. cluster formation.

Co nanoparticles were produced and characterized on protonated titanate nanowires. Co deposits were obtained after low-temperature decomposition of Co2(CO)8 on titanate nanostructures. The carbonylation was carried out by vapor-phase adsorption in a fluidized bed reactor and the decarbonylation processes were followed by FT-IR spectroscopy and microbalance combined with temperature programmed reaction mass spectrometry. The band gap of Co-decorated titanate nanostructures determined by UV-VIS diffuse reflectance spectroscopy decreased sharply from 3.14 eV to 2.41 eV with increasing Co content up to 2 wt%. The Co-decorated titanate morphology was characterized by high-resolution transmission electron microscopy (HRTEM) and electron diffraction (ED). The chemical environment of Co deposition was studied by photoelectron spectroscopy (XPS). A certain amount of cobalt underwent an ion exchange process. Higher cobalt loadings led to the formation of nanosized-dispersed particles complexed to oxygen vacancies. The average sizes were found to be mostly between 2 and 6 nm. This size distribution and the measured band gap could be favorable regimes for some important low-temperature thermal- and photo-induced catalytic reactions.

Fine tuning the surface acidity of titanate nanostructures

The effect of protonation on the surface acidic properties of titanate nanowires (TiONWs) was investigated. Nanowires were synthesized by the alkali hydrothermal method which resulted in one dimensional nanostructures of large external surface area and well-defined lamellar interlayer structure. The Na+/H+ ratio in the structure can be tuned by ion-exchange. Our aim was to characterize the morphology of the as-synthesized nanostructures by HRTEM and SEM measurements and assess their surface acidity using in situ infrared spectroscopic measurements and temperature programmed desorption. It was found that the numbers of Lewis and Brönsted acidic sites in the Na-form and the H-form of the TiONWs is different. The ratio and the nature of acidic sites can be tuned by the ion exchange process. The wire-like morphology and the tunable acidity are features of titanate nanowires that may render them a promising material in various heterogeneous catalytic applications.

A novel carbon tipped single micro-optrode for combined optogenetics and electrophysiology

Optical microelectrodes (optrodes) are used in neuroscience to transmit light into the brain of a genetically modified animal to evoke and record electrical activity from light-sensitive neurons. Our novel micro-optrode solution integrates a light-transmitting 125 micrometer optical fiber and a 9 micrometer carbon monofilament to form an electrical lead element, which is contained in a borosilicate glass sheathing coaxial arrangement ending with a micrometer-sized carbon tip. This novel unit design is stiff and slender enough to be used for targeting deep brain areas, and may cause less tissue damage compared with previous models. The center-positioned carbon fiber is less prone to light-induced artifacts than side-lit metal microelectrodes previously presented. The carbon tip is capable of not only recording electrical signals of neuronal origin but can also provide valuable surface area for electron transfer, which is essential in electrochemical (voltammetry, amperometry) or microbiosensor applications. We present details of design and manufacture as well as operational examples of the newly developed single micro-optrode, which includes assessments of 1) carbon tip length–impedance relationship, 2) light transmission capabilities, 3) photoelectric artifacts in carbon fibers, 4) responses to dopamine using fast-scan cyclic voltammetry in vivo, and 5) optogenetic stimulation and spike or local field potential recording from the rat brain transfected with channelrhodopsin-2. With this work, we demonstrate that our novel carbon tipped single micro-optrode may open up new avenues for use in optogenetic stimulation when needing to be combined with extracellular recording, electrochemical, or microbiosensor measurements performed on a millisecond basis.