Gold nano-mesh synthesis by continuous-flow X-ray irradiation.

X-ray irradiation has been extensively used in recent years as a fabrication step for nanoparticles and nanoparticle systems. A variant of this technique, continuous-flow X-ray irradiation, has recently been developed, and offers three important advantages: precise control of the irradiation dose, elimination of convection effects in the precursor solution, and suitability for large-scale production. Here, the use of this method to fabricate Au nano-meshes of interest as transparent and flexible electrodes for optoelectronics is reported. The study includes extensive characterization of the synthesis parameters and of the product properties, with rather encouraging results.

X-ray irradiation synthesis of PEG-coated Au-Pd nanoparticles.

We demonstrate that the combination of x-ray irradiation and capping by polyethylene glycol (PEG) produces excellent flexibility in controlling the structure of Au-Pd nanoparticles while preserving their catalytic performance. We specifically adopted two different fabrication methods: co-reduction and seed-assisted reduction. In both cases, precursor composition plays an important role in controlling the phases and size of the bimetallic nanoparticles. The optimal catalytic performance is obtained with the highest Pd concentration and when the nanoparticles consist of a Au core and a Pd shell.

Gold nanoparticles as multimodality imaging agents for brain gliomas.

BACKGROUND: Nanoparticles can be used for targeted drug delivery, in particular for brain cancer therapy. However, this requires a detailed analysis of nanoparticles from the associated microvasculature to the tumor, not easy because of the required high spatial resolution. The objective of this study is to demonstrate an experimental solution of this problem, based in vivo and post-mortem whole organ imaging plus nanoscale 3-dimensional (3D) X-ray microscopy. RESULTS: The use of gold nanoparticles (AuNPs) as contrast agents paved the way to a detailed high-resolution three dimensional (3D) X-ray and fluorescence imaging analysis of the relation between xenografted glioma cells and the tumor-induced angiogenic microvasculature. The images of the angiogenic microvessels revealed nanoparticle leakage. Complementary tests showed that after endocytotic internalization fluorescent AuNPs allow the visible-light detection of cells. CONCLUSIONS: AuNP-loading of cells could be extended from the case presented here to other imaging techniques. In our study, they enabled us to (1) identify primary glioma cells at inoculation sites in mice brains; (2) follow the subsequent development of gliomas. (3) Detect the full details of the tumor-related microvasculature; (4) Finding leakage of AuNPs from the tumor-related vasculature, in contrast to no leakage from normal vasculature.

Gold nanoparticles as high-resolution X-ray imaging contrast agents for the analysis of tumor-related micro-vasculature.

BACKGROUND: Angiogenesis is widely investigated in conjunction with cancer development, in particular because of the possibility of early stage detection and of new therapeutic strategies. However, such studies are negatively affected by the limitations of imaging techniques in the detection of microscopic blood vessels (diameter 3-5 µm) grown under angiogenic stress. We report that synchrotron-based X-ray imaging techniques with very high spatial resolution can overcome this obstacle, provided that suitable contrast agents are used. RESULTS: We tested different contrast agents based on gold nanoparticles (AuNPs) for the detection of cancer-related angiogenesis by synchrotron microradiology, microtomography and high resolution X-ray microscopy. Among them only bare-AuNPs in conjunction with heparin injection provided sufficient contrast to allow in vivo detection of small capillary species (the smallest measured lumen diameters were 3-5 µm). The detected vessel density was 3-7 times higher than with other nanoparticles. We also found that bare-AuNPs with heparin allows detecting symptoms of local extravascular nanoparticle diffusion in tumor areas where capillary leakage appeared. CONCLUSIONS: Although high-Z AuNPs are natural candidates as radiology contrast agents, their success is not guaranteed, in particular when targeting very small blood vessels in tumor-related angiography. We found that AuNPs injected with heparin produced the contrast level needed to reveal--for the first time by X-ray imaging--tumor microvessels with 3-5 µm diameter as well as extravascular diffusion due to basal membrane defenestration. These results open the interesting possibility of functional imaging of the tumor microvasculature, of its development and organization, as well as of the effects of anti-angiogenic drugs.

The Associations Between Psychological Distress and Academic Burnout: A Mediation and Moderation Analysis.

Background: Psychological distress is reported to be associated with academic burnout in students while the mediation and moderation effect of resilience and personality are less explored. Purpose: The current study was designed to estimate the mediating effect of resilience and the moderation effect of personality between psychological distress and academic burnout. Participants and methods: A total of 613 students were enrolled from two medical universities between December 2020 and January 2021. They were administered with Academic Burnout Scale, 10-item Kessler Psychological Distress Scale (K10), Connor-Davidson Resilience Scale (CD-RISC-10) and NEO Five-Factor Inventory (NEO-FFI). Latent profile analysis and moderated mediation analysis were performed. Results: Three personalities were identified and named as resilient (13.4%), over-controlled (50.2%) and under-controlled (36.4%). Resilience significantly mediated the relationship between psychological distress and academic burnout while personality significantly moderated the relationship between psychological distress and resilience. Conclusion: Resilience and personality may be two important mediators between psychological distress and academic burnout. More attentions should be paid to students with under-controlled personality and resilience-enhancing interventions could be developed to prevent or alleviate academic burnout in future research.

One-pot tuning of Au nucleation and growth: from nanoclusters to nanoparticles.

We describe a simple and effective method to obtain colloidal surface-functionalized Au nanoparticles. The method is primarily based on irradiation of a gold solution with high-flux X-rays from a synchrotron source in the presence of 11-mercaptoundecanoic acid (MUA). Extensive tests of the products demonstrated high colloidal density as well as excellent stability, shelf life, and biocompatibility. Specific tests with X-ray diffraction, UV-visible spectrometry, visible microscopy, Fourier transform infrared spectroscopy, dark-field visible-light scattering microscopy, and transmission electron microscopy demonstrated that MUA, being an effective surfactant, not only allows tunable size control of the nanoparticles, but also facilitates functionalization. The nanoparticle sizes were 6.45 ± 1.58, 1.83 ± 1.21, 1.52 ± 0.37 and 1.18 ± 0.26 nm with no MUA and with MUA-to-Au ratios of 1:2, 1:1, and 3:1. The MUA additionally enabled functionalization with l-glycine. We thus demonstrated flexibility in controlling the nanoparticle size over a large range with narrow size distribution.

One-pot synthesis of AuPt alloyed nanoparticles by intense x-ray irradiation.

We synthesized AuPt alloyed nanoparticles in colloidal solution by a one-pot procedure based on synchrotron x-ray irradiation in the presence of PEG (polyethylene glycol). The exclusive presence of alloyed nanoparticles with fcc structure was confirmed by several different experiments including UV-vis spectroscopy, x-ray diffraction (XRD) and transmission electron microscopy (TEM). The composition of the AuPt alloyed nanoparticles can be varied in a continuous fashion by simply varying the feed ratios of Au and Pt precursors. The nanoparticles exhibited colloidal stability and biocompatibility, important for potential applications.

Imaging the cellular uptake of tiopronin-modified gold nanoparticles.

Well-dispersed gold nanoparticles (NP) coated with tiopronin were synthesized by X-ray irradiation without reducing agents. High-resolution transmission electron microscopy shows that the average core diameters of the NPs can be systematically controlled by adjusting the tiopronin to Au mole ratio in the reaction. Three methods were used to study the NP uptake by cells: quantitative measurements by inductively coupled plasma mass spectrometry, direct imaging with high lateral resolution transmission electron microscopy and transmission X-ray microscopy. The results confirmed that the NP internalization mostly occurred via endocytosis and concerned the cytoplasm. The particles, in spite of their small sizes, were not found to arrive inside the cell nuclei. The synthesis without reducing agents and solvents increased the biocompatibility as required for potential applications in analysis and biomedicine in general.

Quantitative analysis of nanoparticle internalization in mammalian cells by high resolution X-ray microscopy.

BACKGROUND: Quantitative analysis of nanoparticle uptake at the cellular level is critical to nanomedicine procedures. In particular, it is required for a realistic evaluation of their effects. Unfortunately, quantitative measurements of nanoparticle uptake still pose a formidable technical challenge. We present here a method to tackle this problem and analyze the number of metal nanoparticles present in different types of cells. The method relies on high-lateral-resolution (better than 30 nm) transmission x-ray microimages with both absorption contrast and phase contrast -- including two-dimensional (2D) projection images and three-dimensional (3D) tomographic reconstructions that directly show the nanoparticles. RESULTS: Practical tests were successfully conducted on bare and polyethylene glycol (PEG) coated gold nanoparticles obtained by x-ray irradiation. Using two different cell lines, EMT and HeLa, we obtained the number of nanoparticle clusters uptaken by each cell and the cluster size. Furthermore, the analysis revealed interesting differences between 2D and 3D cultured cells as well as between 2D and 3D data for the same 3D specimen. CONCLUSIONS: We demonstrated the feasibility and effectiveness of our method, proving that it is accurate enough to measure the nanoparticle uptake differences between cells as well as the sizes of the formed nanoparticle clusters. The differences between 2D and 3D cultures and 2D and 3D images stress the importance of the 3D analysis which is made possible by our approach.

Tailored Au nanorods: optimizing functionality, controlling the aspect ratio and increasing biocompatibility.

Monodisperse gold nanorods with high aspect ratio were synthesized by x-ray irradiation. Irradiation was first used to stimulate the creation of seeds. Afterward, nanorod growth was stimulated either by chemical reduction or again by x-ray irradiation. In the last case, the entire process took place without reducing agents. The shape of the final products could be controlled by modulating the intensity of the x-ray irradiation during the seed synthesis. In turn, the nanorod aspect ratio determines the absorption wavelength of the nanorods that can thus be optimized for different applications. Likewise, the aspect ratio influences the uptake of the nanorods by HeLa cells.

Toxic Effects of Size-tunable Gold Nanoparticles on Caenorhabditis elegans Development and Gene Regulation.

We utilized size-tunable gold nanoparticles (Au NPs) to investigate the toxicogenomic responses of the model organism Caenorhabditis elegans. We demonstrated that the nematode C. elegans can uptake Au NPs coated with or without 11-mercaptoundecanoic acid (MUA), and Au NPs are detectable in worm intestines using X-ray microscopy and confocal optical microscopy. After Au NP exposure, C. elegans neurons grew shorter axons, which may have been related to the impeded worm locomotion behavior detected. Furthermore, we determined that MUA to Au ratios of 0.5, 1 and 3 reduced the worm population by more than 50% within 72 hours. In addition, these MUA to Au ratios reduced the worm body size, thrashing frequency (worm mobility) and brood size. MTT assays were employed to analyze the viability of cultured C. elegans primary neurons exposed to MUA-Au NPs. Increasing the MUA to Au ratios increasingly reduced neuronal survival. To understand how developmental changes (after MUA-Au NP treatment) are related to changes in gene expression, we employed DNA microarray assays and identified changes in gene expression (e.g., clec-174 (involved in cellular defense), cut-3 and fil-1 (both involved in body morphogenesis), dpy-14 (expressed in embryonic neurons), and mtl-1 (functions in metal detoxification and homeostasis)).

Optimization of gold nanoparticle photoluminescence by alkanethiolation.

Surface thiolation affects the size of gold nanoparticles and the presence of visible luminescence under UV stimulation. We explored these phenomena by analysing alkanethiolate coatings with different carbon chain lengths, from 3-mercaptopropionic acid to 16-mercaptohexadecanoic acid, synthesized by intense X-ray irradiation. Photoluminescence is present for the smallest nanoparticles, but its intensity becomes more intense as the carbon chain length increases, achieving a quantum efficiency of 28% with a 16-mercaptohexadecanoic acid coating.

Very small photoluminescent gold nanoparticles for multimodality biomedical imaging.

An original synthesis method based on X-ray irradiation produced gold nanoparticles (AuNPs) with two important properties for biomedical research: intense visible photoluminescence and very high accumulation in cancer cells. The nanoparticles, coated with MUA (11-mercaptoundecanoid acid), are very small (1.4 nm diameter); the above two properties are not present for even slightly larger sizes. The small MUA-AuNPs are non-cytotoxic (except for very high concentrations) and do not interfere with cancer cell proliferation. Multimodality imaging using visible light fluorescence and X-ray microscopy is demonstrated by tracing the nanoparticle-loaded tumor cells.

X-ray imaging of tumor growth in live mice by detecting gold-nanoparticle-loaded cells.

We show that sufficient concentrations of gold nanoparticles produced by an original synthesis method in EMT-6 and CT-26 cancer cells make it possible to detect the presence, necrosis and proliferation of such cells after inoculation in live mice. We first demonstrated that the nanoparticles do not interfere with the proliferation process. Then, we observed significant differences in the tumor evolution and the angiogenesis process after shallow and deep inoculation. A direct comparison with pathology optical images illustrates the effectiveness of this approach.

Enhancement of irradiation effects on cancer cells by cross-linked dextran-coated iron oxide (CLIO) nanoparticles.

We investigated iron oxide nanoparticles with two different surface modifications, dextran coating and cross-linked dextran coating, showing that their different internalization affects their capability to enhance radiation damage to cancer cells. The internalization was monitored with an ultrahigh resolution transmission x-ray microscope (TXM), indicating that the differences in the particle surface charge play an essential role and dominate the particle-cell interaction. We found that dextran-coated iron oxide nanoparticles cannot be internalized by HeLa and EMT-6 cells without being functionalized with amino groups (the cross-linked dextran coating) that modify the surface potential from -18 mV to 13.4 mV. The amount of cross-linked dextran-coated iron oxide nanoparticles uptaken by cancer cells reached its maximum, 1.33 x 10(9) per HeLa cell, when the co-culture concentration was 40 microg Fe mL(-1) or more. Standard tests indicated that these internalized nanoparticles increased the damaging effects of x-ray irradiation, whereas they are by themselves biocompatible. These results could lead to interesting therapy applications; furthermore, iron oxide also produces high contrast for magnetic resonance imaging (MRI) in the diagnosis and therapy stages.