Surface Chemistry and Specific Surface Area Rule the Efficiency of Gold Nanoparticle Sensitizers in Proton Therapy.

Gold nanoparticles (AuNPs) are currently the most studied radiosensitizers in proton therapy (PT) applicable for the treatment of solid tumors, where they amplify production of reactive oxygen species (ROS). However, it is underexplored how this amplification is correlated with the AuNPs' surface chemistry. To clarify this issue, we fabricated ligand-free AuNPs of different mean diameters by laser ablation in liquids (LAL) and laser fragmentation in liquids (LFL) and irradiated them with clinically relevant proton fields by using water phantoms. ROS generation was monitored by the fluorescent dye 7-OH-coumarin. Our findings reveal an enhancement of ROS production driven by I) increased total particle surface area, II) utilization of ligand-free AuNPs avoiding sodium citrate as a radical quencher ligands, and III) a higher density of structural defects generated by LFL synthesis, indicated by surface charge density. Based on these findings it may be concluded that the surface chemistry is a major and underexplored contributor to ROS generation and sensitizing effects of AuNPs in PT. We further highlight the applicability of AuNPs in vitro in human medulloblastoma cells.

Automated classification of nanoparticles with various ultrastructures and sizes via deep learning.

Accurately measuring the size, morphology, and structure of nanoparticles is very important, because they are strongly dependent on their properties for many applications. In this paper, we present a deep-learning based method for nanoparticle measurement and classification trained from a small data set of scanning transmission electron microscopy images including overlapping nanoparticles. Our approach is comprised of two stages: localization, i.e., detection of nanoparticles, and classification, i.e., categorization of their ultrastructure. For each stage, we optimize the segmentation and classification by analysis of the different state-of-the-art neural networks. We show how the generation of synthetic images, either using image processing or using various image generation neural networks, can be used to improve the results in both stages. Finally, the application of the algorithm to bimetallic nanoparticles demonstrates the automated data collection of size distributions including classification of complex ultrastructures. The developed method can be easily transferred to other material systems and nanoparticle structures.

Impact of Sterilization on the Colloidal Stability of Ligand-Free Gold Nanoparticles for Biomedical Applications.

Sterilization is a major prerequisite for the utilization of nanoparticle colloids in biomedicine, a process well examined for particles derived from chemical synthesis although highly underexplored for electrostatically stabilized ligand-free gold nanoparticles (AuNPs). Hence, in this work, we comprehensively examined and compared the physicochemical characteristics of laser-generated ligand-free colloidal AuNPs exposed to steam sterilization and sterile filtration as a function of particle size and mass concentration and obtained physicochemical insight into particle growth processes. These particles exhibit long-term colloidal stability (up to 3 months) derived from electrostatic stabilization without using any ligands or surfactants. We show that particle growth attributed to cluster-based ripening occurs in smaller AuNPs (∼5 nm) following autoclaving, while larger particles (∼10 and ∼30 nm) remain stable. Sterile filtration, as an alternative effective sterilizing approach, has no substantial impact on the colloidal stability of AuNPs, regardless of particle size, although a mass loss of 5-10% is observed. Finally, we evaluated the impact of the sterilization procedures on potential particle functionality in proton therapy, using the formation of reactive oxygen species (ROS) as a readout. In particular, 5 nm AuNPs exhibit a significant loss in activity upon autoclaving, probably dedicated to specific surface area reduction and surface restructuring during particle growth. The filtered analog enhanced the ROS release by up to a factor of ∼2.0, at 30 ppm gold concentration. Our findings highlight the need for carefully adapting the sterilization procedure of ligand-free NPs to the desired biomedical application with special emphasis on particle size and concentration.

Enhancement of Proton Therapy Efficiency by Noble Metal Nanoparticles Is Driven by the Number and Chemical Activity of Surface Atoms.

Proton-based radiotherapy is a modern technique for the treatment of solid tumors with significantly reduced side effects to adjacent tissues. Biocompatible nanoparticles (NPs) with high atomic numbers are known to serve as sensitizers and to enhance treatment efficacy, which is commonly believed to be attributed to the generation of reactive oxygen species (ROS). However, little systematic knowledge is available on how either physical effects due to secondary electron generation or the particle surface chemistry affect ROS production. Thereto, ligand-free colloidal platinum (Pt) and gold (Au) NPs with well-controlled particle size distributions and defined total surface area are proton-irradiated. A fluorescence-based assay is developed to monitor the formation of ROS using terephthalic acid as a cross-effect-free dye. The findings indicate that proton irradiation (PI)-induced ROS formation sensitized by noble metal NPs is driven by the total available particle surface area rather than particle size or mass. Furthermore, a distinctive material effect with Pt being more active than Au is observed which clearly indicates that the chemical reactivity of the NP surface is a main contributor to ROS generation upon PI. These results pave the way towards an in-depth understanding of the NP-induced sensitizing effects upon PI and hence a well-controlled enhanced therapy.

Impact of activator incorporation on red emitting rods of ZnGa2O4:Cr3+ phosphor.

Chromium doped zinc gallium oxide (ZnGa2O4:Cr3+) microrods were synthesized by simple solid state reaction method. The transformation on crystal structure and optical properties with molar concentration of Cr3+ were analyzed. The cubic spinel nature of ZnGa2O4:Cr3+phosphor and their crystalline nature were confirmed from x- ray diffractogram. The average grain size of the samples range between 24 and 29 nm, with lattice parameter values greater than that of bulk. Lattice strain produced in the lattice on doping was estimated from the Williamson-Hall plot. It increases on Cr3+ doping up to 3 mol% and then decreases. Rod like nature of zinc gallate was observed from the surface morphological analysis using SEM. X-ray photoelectron spectroscopy was used for the chemical state identification of the constituent elements in the compound. The photoluminescense spectra consists of various emission lines originated from the chromium ion in the spinel lattice. The purity of red emissions were observed from chromaticity diagram with a concentration quenching initiated from the dipole-dipole interaction, with increase in dopant concentration. Band gap of the samples were estimated using Kubelka-Munk equation which exhibited red shift compared to bulk due to band tailing effect.

Nanostructured SnS2 Thin Films from Laser Ablated Nanocolloids: Structure, Morphology, Optoelectronic and Electrochemical Properties.

Tin disulfide (SnS2 ) is a binary chalcogenide semiconductor having applications in solar cells, energy storage, and optoelectronics. SnS2 thin films were deposited by spraying the nanocolloids synthesized by pulsed laser ablation in liquid. The structure, morphology, and optoelectronic properties were studied for films obtained from two liquid media (ethanol and isopropanol) and after heat treatments at various temperatures. X-ray diffraction analysis confirmed the hexagonal crystal structure of the films, whereas the 2-H polytype structure was identified by micro-Raman spectroscopy. Oxidation states of Sn (4+) and S (2-) identified from high resolution X-ray photoelectron spectra confirmed the composition and chemical states of the films. The SnS2 thin films exhibited distinct porous surface morphologies as the liquid medium in laser ablation was varied. All as-prepared and annealed films showed photoluminescence with a high intensity peak at 485 nm and a low intensity peak at 545 nm. Thin films annealed at 300 °C showed improved electrochemical properties upon illumination using a blue LED light source. Current-voltage curves recorded in dark and light as well as the photoresponse measurements showed their suitability for utilization in optoelectronic devices. The results of this study may trigger further research towards fabrication of nanostructured thin films in large area for optoelectronic and photoelectrochemical applications in an environment friendly and cost-effective way.

Synthesis of surfactant free stable nanofluids based on barium hexaferrite by pulsed laser ablation in liquid.

Barium hexaferrite nanofluids based on five different solvents have been prepared by employing Pulsed Laser Ablation in Liquid (PLAL) at two different wavelengths of 532 nm and 1064 nm. They were then characterized using Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), X-ray Photoelectron Spectroscopy (XPS), UV-Vis spectroscopy, and Vibrating Sample Magnetometry (VSM). The chemical states of the ablated nanoparticles were identified from XPS analysis and found to be matching with that of the target. The crystallinity of the nanoparticles were confirmed from high resolution TEM (HRTEM) images and SAED patterns. It is found that different liquid environments lead to the formation of barium ferrite nanoparticles with different particle diameters. The plausible mechanism involved in this process is discussed. This study can pave way for the synthesis of stable magnetic nanofluids of permanent magnets. Further, this technique could be utilized for tailoring the morphology of nanoparticles with a judicious choice of the solvents and other ablation parameters.

Synthesis and Properties of Tin Sulfide Thin Films from Nanocolloids Prepared by Pulsed Laser Ablation in Liquid.

Tin sulfide (SnS) nanoparticles were synthesized by pulsed laser ablation in liquid (PLAL) technique using an Nd:YAG laser operated at 532 nm. SnS thin films were deposited by spraying the colloidal suspension onto the heated substrates. The influence of different liquid media (dimethyl formamide and isopropyl alcohol) on the thin film properties were studied. Morphology, crystalline structure, and chemical composition of the nanoparticles were identified using transmission electron microscopy with energy dispersive X-ray analysis. The crystalline structure of the thin films was analyzed by using grazing incidence X-ray diffraction, and the chemical states by X-ray photoelectron spectroscopy. Scanning electron microscopy was employed for the morphological analysis of the thin films. Annealing the films at 380 °C improved the crystallinity of the films exhibiting a layered morphology, which may be useful in optoelectronic and sensing applications. Cyclic voltammetry studies showed that the films have good electrochemical properties.