Nanoscale Control of Structure and Composition for Nanocrystalline Fe Thin Films Grown by Oblique Angle RF Sputtering.

The use of Fe films as multi-element targets in space radiation experiments with high-intensity ultrashort laser pulses requires a surface structure that can enhance the laser energy absorption on target, as well as a low concentration and uniform distribution of light element contaminants within the films. In this paper, (110) preferred orientation nanocrystalline Fe thin films with controlled morphology and composition were grown on (100)-oriented Si substrates by oblique angle RF magnetron sputtering, at room temperature. The evolution of films key-parameters, crucial for space-like radiation experiments with organic material, such as nanostructure, morphology, topography, and elemental composition with varying RF source power, deposition pressure, and target to substrate distance is thoroughly discussed. A selection of complementary techniques was used in order to better understand this interdependence, namely X-ray Diffraction, Atomic Force Microscopy, Scanning and Transmission Electron Microscopy, Energy Dispersive X-ray Spectroscopy and Non-Rutherford Backscattering Spectroscopy. The films featured a nanocrystalline, tilted nanocolumn structure, with crystallite size in the (110)-growth direction in the 15-25 nm range, average island size in the 20-50 nm range, and the degree of polycrystallinity determined mainly by the shortest target-to-substrate distance (10 cm) and highest deposition pressure (10-2 mbar Ar). Oxygen concentration (as impurity) into the bulk of the films as low as 1 at. %, with uniform depth distribution, was achieved for the lowest deposition pressures of (1-3) × 10-3 mbar Ar, combined with highest used values for the RF source power of 125-150 W. The results show that the growth process of the Fe thin film is strongly dependent mainly on the deposition pressure, with the film morphology influenced by nucleation and growth kinetics. Due to better control of film topography and uniform distribution of oxygen, such films can be successfully used as free-standing targets for high repetition rate experiments with high power lasers to produce Fe ion beams with a broad energy spectrum.

Focused ultrasound radiosensitizes human cancer cells by enhancement of DNA damage.

PURPOSE: High-intensity focused ultrasound (HIFU/FUS) has expanded as a noninvasive quantifiable option for hyperthermia (HT). HT in a temperature range of 40-47 °C (thermal dose CEM43 ≥ 25) could work as a sensitizer to radiation therapy (RT). Here, we attempted to understand the tumor radiosensitization effect at the cellular level after a combination treatment of FUS+RT. METHODS: An in vitro FUS system was developed to induce HT at frequencies of 1.147 and 1.467 MHz. Human head and neck cancer (FaDU), glioblastoma (T98G), and prostate cancer (PC-3) cells were exposed to FUS in ultrasound-penetrable 96-well plates followed by single-dose X­ray irradiation (10 Gy). Radiosensitizing effects of FUS were investigated by cell metabolic activity (WST­1 assay), apoptosis (annexin V assay, sub-G1 assay), cell cycle phases (propidium iodide staining), and DNA double-strand breaks (γH2A.X assay). RESULTS: The FUS intensities of 213 (1.147 MHz) and 225 W/cm2 (1.467 MHz) induced HT for 30 min at mean temperatures of 45.20 ± 2.29 °C (CEM43 = 436 ± 88) and 45.59 ± 1.65 °C (CEM43 = 447 ± 79), respectively. FUS improves the effect of RT significantly by reducing metabolic activity in T98G cells 48 h (RT: 96.47 ± 8.29%; FUS+RT: 79.38 ± 14.93%; p = 0.012) and in PC-3 cells 72 h (54.20 ± 10.85%; 41.01 ± 11.17%; p = 0.016) after therapy, but not in FaDu cells. Mechanistically, FUS+RT leads to increased apoptosis and enhancement of DNA double-strand breaks compared to RT alone in T98G and PC-3 cells. CONCLUSION: Our in vitro findings demonstrate that FUS has good potential to sensitize glioblastoma and prostate cancer cells to RT by mainly enhancing DNA damage.

Laser-driven radiation: Biomarkers for molecular imaging of high dose-rate effects.

Recently developed short-pulsed laser sources garner high dose-rate beams such as energetic ions and electrons, x rays, and gamma rays. The biological effects of laser-generated ion beams observed in recent studies are different from those triggered by radiation generated using classical accelerators or sources, and this difference can be used to develop new strategies for cancer radiotherapy. High-power lasers can now deliver particles in doses of up to several Gy within nanoseconds. The fast interaction of laser-generated particles with cells alters cell viability via distinct molecular pathways compared to traditional, prolonged radiation exposure. The emerging consensus of recent literature is that the differences are due to the timescales on which reactive molecules are generated and persist, in various forms. Suitable molecular markers have to be adopted to monitor radiation effects, addressing relevant endogenous molecules that are accessible for investigation by noninvasive procedures and enable translation to clinical imaging. High sensitivity has to be attained for imaging molecular biomarkers in cells and in vivo to follow radiation-induced functional changes. Signal-enhanced MRI biomarkers enriched with stable magnetic nuclear isotopes can be used to monitor radiation effects, as demonstrated recently by the use of dynamic nuclear polarization (DNP) for biomolecular observations in vivo. In this context, nanoparticles can also be used as radiation enhancers or biomarker carriers. The radiobiology-relevant features of high dose-rate secondary radiation generated using high-power lasers and the importance of noninvasive biomarkers for real-time monitoring the biological effects of radiation early on during radiation pulse sequences are discussed.

Dose calculations in a cell monolayer for high-throughput irradiation with proton beams generated by PW lasers for space applications.

One of the specific properties of laser-driven radiation is a broadband energy spectrum, which is also a feature of the space radiation fields. This property can be used in materials science studies or radiobiology experiments to simulate the energy spectrum of space radiation exposures in a ground-based laboratory. However, the differences in effects between the higher dose rates of laser generated radiation and the lower dose rates of space radiation have to be investigated in separate, prior studies. A design for a high-throughput irradiation experiment and the associated Monte Carlo dose calculations for a broadband energy proton beam depositing energy in a cell monolayer is presented. Dose control and dose uniformity in the cell monolayer was achieved in the simulations using a variable thickness Ni attenuator. A set of target doses from 0.2 Gy to 4 Gy was obtained and dose uniformity was optimized to less than 4% variability. This work opens the possibility of single or multiple exposures, controllable, high-throughput irradiation experiments on biological samples or materials, using broadband energy particle beams generated by lasers, with relevance for space applications.

Thermometry during MR-guided focused ultrasound in a preclinical model based on Thiel embalmed tissue.

BACKGROUND: The purpose of this work was to determine the accuracy of Proton Resonance Frequency (PRF) thermometry during MR-guided Focused Ultrasound (MRgFUS) ablation on explanted Thiel embalmed human and animal liver, fresh animal liver, and compared to gel phantom. MATERIAL AND METHODS: PRF thermometry during MRgFUS was conducted using a 1.5T MRI system. The phantom and the organs were sonicated with the following energies: 300J, 600J, 1000J and 1400J. The temperature increase which was measured using PRF thermometry during sonication was compared to actual temperature rise in the same conditions measured by fibre optic thermocouple. RESULTS: Sonication of fresh animal liver showed temperature differences varying between 0.27°C and 0.40°C, whereas the phantom results showed temperature differences from 0.23°C to 0.40°C. For the Thiel embalmed organs, the temperature difference varied from 1.17 °C to 3.13°C for the ovine liver, and from 1.3°C to 3.10°C for the human liver. CONCLUSION: The temperature differences measured in the fresh liver were small and similar to those found for the gel phantom. However, the temperature differences calculated for the Thiel embalmed organs were higher compared to the fresh organ. This indicates that the PRF-based temperature calibration of the Focused Ultrasound machine for Thiel embalmed tissue is necessary.

Biomimetic high density lipoprotein nanoparticles for nucleic acid delivery.

We report a gold nanoparticle-templated high density lipoprotein (HDL AuNP) platform for gene therapy that combines lipid-based nucleic acid transfection strategies with HDL biomimicry. For proof-of-concept, HDL AuNPs are shown to adsorb antisense cholesterylated DNA. The conjugates are internalized by human cells, can be tracked within cells using transmission electron microscopy, and regulate target gene expression. Overall, the ability to directly image the AuNP core within cells, the chemical tailorability of the HDL AuNP platform, and the potential for cell-specific targeting afforded by HDL biomimicry make this platform appealing for nucleic acid delivery.