Unveiling Nanoparticles: Recent Approaches in Studying the Internalization Pattern of Iron Oxide Nanoparticles in Mono- and Multicellular Biological Structures.

Nanoparticle (NP)-based solutions for oncotherapy promise an improved efficiency of the anticancer response, as well as higher comfort for the patient. The current advancements in cancer treatment based on nanotechnology exploit the ability of these systems to pass biological barriers to target the tumor cell, as well as tumor cell organelles. In particular, iron oxide NPs are being clinically employed in oncological management due to this ability. When designing an efficient anti-cancer therapy based on NPs, it is important to know and to modulate the phenomena which take place during the interaction of the NPs with the tumor cells, as well as the normal tissues. In this regard, our review is focused on highlighting different approaches to studying the internalization patterns of iron oxide NPs in simple and complex 2D and 3D in vitro cell models, as well as in living tissues, in order to investigate the functionality of an NP-based treatment.

Impact of 3MeV Energy Proton Particles on Mid-IR QCLs.

This paper reports the results obtained for a distributed-feedback quantum cascade laser (DFB-QCL) exposed to different fluences of proton particles: 1014, 1015 and 1016 p/cm2. Dedicated laboratory setups were developed to assess the irradiation-induced changes in this device. Multiple parameters defining the QCL performances were investigated prior to and following each irradiation step: (i) voltage-driving current; (ii) emitted optical power-driving current; (iii) central emitting wavelength-driving current; (iv) emitted spectrum-driving current; (v) transversal mode structure-driving current, maintaining the system operating temperature at 20 °C. The QCL system presented, before irradiation, two emission peaks: a central emission peak and a side peak. After proton irradiation, the QCL presented a spectral shift, and the ratio between the two peaks also changed. Even though, after irradiation, the tunning spectral range was reduced, at the end of the tests, the system was still functional.

Helium Atmospheric Pressure Plasma Jet Effects on Two Cultivars of Triticum aestivum L.

The use of cold plasma in the treatment of seeds before sowing presents a promising technique for sustainable agriculture. The objective of this study is to evaluate the effect of cold plasma treatment on the morphology of wheat seeds (Triticum aestivum L. 'Dacic' and 'Otilia'), their germination, biochemical composition, and the nutritional quality of wheat grass. Wheat seeds were morphologically and elementally characterized by atomic force microscopy (AFM), scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX), X-ray computer tomography (CT), and particle-induced X-ray emission (PIXE). Helium was used as a working gas for plasma generation and the analysis of the species produced showed the presence of NOγ, OH, N2 and N2+ and O. Evaluation of germination and plant growth for 10 days (wheat grass stage) highlighted a specific trend for each cultivar. The biochemical analysis of wheat grass highlighted an increase in the chlorophyll content in the plasma-treated variants, an increase in the flavonoid and polyphenol content in 'Dacic'-treated variant, while the soluble protein content, antioxidant activity, and color were not affected. The analysis of the nutritional quality of wheat grass by the FT-NIR analytical technique highlighted an increase in the ash content in the plasma-treated wheat cultivars, while the humidity, proteins, neutral detergent fiber (NDF), acid detergent fiber (ADF), and energy values were not affected.

Proton irradiation induced reactive oxygen species promote morphological and functional changes in HepG2 cells.

The increased use of proton therapy has led to the need of better understanding the cellular mechanisms involved. The aim of this study was to investigate the effects induced by the accelerated proton beam in hepatocarcinoma cells. An existing facility in IFIN-HH, a 3 MV Tandetron™ accelerator, was used to irradiate HepG2 human hepatocarcinoma cells with doses between 0 and 3 Gy. Colony formation was used to assess the influence of radiation on cell long-term replication. Also, the changes induced at the mitochondrial level were shown by increased ROS and ATP levels as well as a decrease in the mitochondrial membrane potential. An increased dose has induced DNA damages and G2/M cell cycle arrest which leads to caspase 3/7 mediated apoptosis and senescence induction. Finally, the morphological and ultrastructural changes were observed at the membrane level and the nucleus of the irradiated cells. Thus, proton irradiation induces both morphological and functional changes in HepG2 cells.

Enhanced Internalization of Nanoparticles Following Ionizing Radiation Leads to Mitotic Catastrophe in MG-63 Human Osteosarcoma Cells.

This study aims to investigate whether ionizing radiation combined with doxorubicin-conjugated iron oxide nanoparticles (NP-DOX) improves the internalization and cytotoxic effects of the nano-carrier-mediated drug delivery in MG-63 human osteosarcoma cells. NP-DOX was designed and synthesized using the co-precipitation method. Highly stable and crystalline nanoparticles conjugated with DOX were internalized in MG-63 cells through macropinocytosis and located in the perinuclear area. Higher nanoparticles internalization in MG-63 cells previously exposed to 1 Gy X-rays was correlated with an early accumulation of cells in G2/M, starting at 12 h after treatment. After 48 h, the application of the combined treatment led to higher cytotoxic effects compared to the individual treatment, with a reduction in the metabolic capacity and unrepaired DNA breaks, whilst a low percent of arrested cells, contributing to the commitment of mitotic catastrophe. NP-DOX showed hemocompatibility and no systemic cytotoxicity, nor histopathological alteration of the main organs.

THE DEVELOPMENT OF A NOVEL ARRAY DETECTOR FOR OVERCOMING THE DOSIMETRY CHALLENGES OF MEASURING IN VERY SHORT PULSED CHARGED PARTICLE BEAMS: THE ELIDOSE PROJECT.

In-beam dose measurements are paramount for any application seeking to harness the effects of the radiation beam, so all the future applications of the laser accelerated beams (as generated in the ELI and CETAL projects) will need such measurements. With a very long history in measuring doses in charged particle beams, the medical and industrial applications setup a number of methods that could be also used for the dosimetry of the beams generated by laser pulses. Dose measurements rely heavily on what is seen as the gold standard in dose measurement: the ion chambers. Ion chambers have both limitations and advantages, and in our case the disadvantage could be the large number of corrections to be applied in order to calculate a correct dose from the measured charge. The ELIDOSE project tries to address these problems by proposing an array detector that would allow the simultaneous measurement of the recombination and polarity corrections, and of the dose. The detector consists of four identical ion chambers mounted together in a PMMA frame and the project will analyze its response to various charged particle beams and the reciprocal influences of the chambers on each other. These reciprocal influences of the four chambers are studied through the FLUKA modeling of the detector and, in order to hone the simulations of the detectors, we initially compared the results of the measurements performed with an Advanced MarkusTM chamber in the proton beam delivered at the 3-MV TandetronTM from IFIN-HH. The paper presents the results of these initial measurements and how these results will be used to modify the simulation parameters.