ORCID Profile
0000-0002-3886-9516
Current Organisation
University of South Australia
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Proteomics and Intermolecular Interactions (excl. Medical Proteomics) | Nuclear physics | Gene Expression (incl. Microarray and other genome-wide approaches) | Nuclear and plasma physics | Law and society and socio-legal research | Colloid and Surface Chemistry | Geochemistry | Environmental Chemistry (incl. Atmospheric Chemistry) | Physical Chemistry (Incl. Structural) | Exploration Geochemistry | Mineral processing/beneficiation |
ANZSRC Socio-Economic Objective (SEO)
Physical and Chemical Conditions of Water in Fresh, Ground and Surface Water Environments (excl. Urban and Industrial Use) | Expanding Knowledge in the Physical Sciences | Expanding Knowledge in the Biological Sciences | Cancer and Related Disorders | Copper Ore Exploration | Environmental Health |
Related Links
Publications
One-pot synthesis of AuPt alloyed nanoparticles by intense x-ray irradiation
Publisher: IOP Publishing
Date: 07-01-2011
DOI: 10.1088/0957-4484/22/6/065605
Abstract: 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.
Synchrotron XPS studies of collector adsorption and co-adsorption on gold and gold: silver alloy surfaces
Publisher: Elsevier BV
Date: 08-2009
Nanoparticle-Based Radiosensitization
Publisher: MDPI AG
Date: 20-04-2020
DOI: 10.3390/IJMS21082879
Abstract: Radiotherapy is a highly multidisciplinary field with respect to its foundations of research and development, and in its clinical utility [...]
In situ analysis of metal(loid)s in plants: State of the art and artefacts
Publisher: Elsevier BV
Date: 08-2011
Immunospecific targeting of CD45 expressing lymphoid cells: Towards improved detection agents of the sentinel lymph node
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.CANLET.2012.09.024
Abstract: This study was designed to demonstrate the potential of small nanoparticulate lymphotropic contrast agents designed to bind with high affinity to lymphoid cells overexpressing the CD45 antigen. To this end, small gold nanoparticles used as model were conjugated to anti-CD45 antibodies and injected in mice in the dorsal toe of the fore/hind paw. Chemical analysis demonstrated rapid uptake and transport of the nanoparticles in the lymphatic as well as significant retention of the nanoparticles with high binding affinity to lymphoid cells in the popliteal and axillary lymph nodes in comparison to non-targeted nanoparticles.
In silico modeling of cellular probabilistic nanoparticle radiosensitization in head and neck cancers
Publisher: Future Medicine Ltd
Date: 12-2020
Abstract: Background: The use of gold nanoparticles (AuNPs) as radiosensitizers may offer a new approach in the treatment of head and neck cancers minimizing treatment-associated toxicities and improving patient outcomes. AuNPs promote localized dose deposition permitting improved local control and/or dose reduction. Aim: This work aimed to address the theoretical optimization of radiation doses, fractionation and nanoparticle injection schedules to maximize therapeutic benefits. Materials & methods: Probabilistic nanoparticle sensitization factors were incorporated into the in idual cell-based HYP-RT computer model of tumor growth and radiotherapy. Results: Total dose outcomes across all radiation therapy treatment regimens were found to be significantly reduced with the presence of AuNPs, with bi-weekly injections showing the most decrease. Conclusion: Outcomes suggest the need for regular AuNP administration to permit effective radiosensitization.
Corrigendum to “Environmental pH-sensitive polymeric nano-carriers for targeted tumor delivery” [J. Control. Release 213 (2015) e46–e47]
Publisher: Elsevier BV
Date: 11-2015
Repolarization of M2 to M1 Macrophages Triggered by Lactate Oxidase Released from Methylcellulose Hydrogel.
Publisher: American Chemical Society (ACS)
Date: 18-09-2019
DOI: 10.1021/ACS.BIOCONJCHEM.9B00618
Abstract: Deregulated proliferation of tumors is generally associated with altered energy metabolism. A high rate of anaerobic glycolysis in solid tumors contributes to an acidification of pH to ∼6.7-7.2 in the tumor microenvironment and lactate accumulation. Macrophages in the tumor microenvironment can be educated by tumor cells. Tumor-derived lactate induces the polarization of M2 macrophages and promotes tumor invasion and metastasis. However, a particular challenge is to sustain lactate depletion. We propose that the repolarization of the tumor-supportive M2 macrophage to the tumor-suppressive M1 macrophage after the depletion of lactate by lactate oxidase (LOX) released from the hydrogels in the tumor microenvironment may enhance the antitumor treatment efficacy.
Quantitative analysis of nanoparticle internalization in mammalian cells by high resolution X-ray microscopy
Publisher: Springer Science and Business Media LLC
Date: 10-04-2011
Abstract: 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. 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. 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.
Surface analysis for compositional, chemical and structural imaging in pharmaceutics with mass spectrometry: a ToF-SIMS perspective
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.IJPHARM.2011.01.043
Abstract: We review the application of time-of-flight secondary-ion mass spectrometry (ToF-SIMS) for the surface chemical identification and distribution analysis (mapping) of pharmaceutically relevant materials. Specifically we explore the characterization of both solid state pharmaceuticals and bio-pharmaceuticals by ToF-SIMS highlighting specific case studies concerning the distribution and stability of pharmaceutical actives within solid matrices, the face-specific properties of pharmaceutical crystals and elucidation of the structure/conformation of adsorbed proteins. Finally, potential future applications of ToF-SIMS in pharmaceutics are detailed.
Imaging the cellular uptake of tiopronin-modified gold nanoparticles
Publisher: Springer Science and Business Media LLC
Date: 03-05-2011
DOI: 10.1007/S00216-011-4986-3
Abstract: 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.
Tailored Au nanorods: optimizing functionality, controlling the aspect ratio and increasing biocompatibility
Publisher: IOP Publishing
Date: 26-07-2010
DOI: 10.1088/0957-4484/21/33/335604
Abstract: 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.
The MTT Assay: A Method for Error Minimization and Interpretation in Measuring Cytotoxicity and Estimating Cell Viability
Publisher: Springer US
Date: 2023
The occurrence and incorporation of copper and zinc in hair and their potential role as bioindicators: A review
Publisher: Informa UK Limited
Date: 23-11-2007
DOI: 10.1080/10937400701389917
Abstract: This article reviews evidence that suggests Cu and Zn concentrations are not altered significantly by exogenous processes and may be useful in applications of hair analysis. The review attempts to identify what Cu and Zn concentrations may actually indicate biogenically and investigates the mechanisms by which they are incorporated into hair. Associations with specific hair components are proposed and avenues for development as a bioindicator are identified. Areas of research that offer promise in application or confirming the use of Cu and Zn are also indicated. Correlations and relationships with other health disorders are reviewed. Endogenous blood concentrations may also explain alterations in hair structure relating to breast cancer.
Potential therapeutics using tumor-secreted lactate in nonsmall cell lung cancer
Publisher: Elsevier BV
Date: 11-2021
The mtt assay: utility, limitations, pitfalls, and interpretation in bulk and single-cell analysis
Publisher: MDPI AG
Date: 26-11-2021
Abstract: The MTT assay for cellular metabolic activity is almost ubiquitous to studies of cell toxicity however, it is commonly applied and interpreted erroneously. We investigated the applicability and limitations of the MTT assay in representing treatment toxicity, cell viability, and metabolic activity. We evaluated the effect of potential confounding variables on the MTT assay measurements on a prostate cancer cell line (PC-3) including cell seeding number, MTT concentration, MTT incubation time, serum starvation, cell culture media composition, released intracellular contents (cell lysate and secretome), and extrusion of formazan to the extracellular space. We also assessed the confounding effect of polyethylene glycol (PEG)-coated gold nanoparticles (Au-NPs) as a tested treatment in PC-3 cells on the assay measurements. We additionally evaluated the applicability of microscopic image cytometry as a tool for measuring intracellular MTT reduction at the single-cell level. Our findings show that the assay measurements are a result of a complicated process dependant on many of the above-mentioned factors, and therefore, optimization of the assay and rational interpretation of the data is necessary to prevent misleading conclusions on variables such as cell viability, treatment toxicity, and/or cell metabolism. We conclude, with recommendations on how to apply the assay and a perspective on where the utility of the assay is a powerful tool, but likewise where it has limitations.
Nanomodified strategies to overcome EGFR-tyrosine kinase inhibitors resistance in non-small cell lung cancer
Publisher: Elsevier BV
Date: 08-2020
Gold nanoparticle enhanced proton therapy: A Monte Carlo simulation of the effects of proton energy, nanoparticle size, coating material, and coating thickness on dose and radiolysis yield
Publisher: Wiley
Date: 02-12-2019
DOI: 10.1002/MP.13923
Abstract: Radiosensitizer enhanced radiotherapy provides the possibility of improved treatment outcomes by preferentially increasing the effectiveness of radiation within the tumor. Proton therapy offers improved sparing of tissue distal of the tumor along the beam path and reduced integral dose compared to conventional photon therapy. The combination of proton therapy with radiosensitizers offers the potential for an enhanced therapy with increased effect within the tumor and low integral dose. The simulations performed in this work determine the effect of nanoparticle characteristics and proton energy on the nanoscale dose and radiolysis yield enhancement for a single gold nanoparticle irradiated with a proton beam. This data can be used to determine optimal nanoparticle characteristics to enhance proton therapy. A two-stage Monte Carlo simulation was performed using Geant4. In the first stage of the simulation, the physical interactions of protons within a gold nanoparticle were modeled and the secondary electrons escaping the nanoparticle's surface were scored in a phase space file. In the second stage of the simulation, the phase space file was used as an input to model the physical interactions of the secondary electrons in water and the resulting production and chemical interactions of reactive species. By comparing a gold nanoparticle with an equivalent water nanoparticle, the nanoscale enhancement of dose and radiolysis yield was calculated. A large nanoscale enhancement of both the dose and radiolysis yield of up to a factor of 11 due to gold nanoparticles was found for most simulated conditions. For 50 nm gold nanoparticles, a large enhancement factor of 9-11 was observed for high proton energies however, the enhancement was reduced for proton energies below 10 MeV. For 5 MeV incident protons, it was found that the enhancement factor was approximately 9 for gold nanoparticles of sizes 5-25 nm with a reduction in enhancement observed for nanoparticle sizes outside this range. Additionally, it was found that larger nanoparticle sizes resulted in greater total energy deposition and radiolysis yields per proton flux but with reduced efficiency per nanoparticle mass. It was observed that a large loss of enhancement occurred for thick nanoparticle coatings. However, for polyethylene glycol (PEG) coatings, coating density had a minimal effect on enhancement. A large enhancement in dose and radiolysis yield was observed. However, the low-energy secondary electrons produced within the gold for lower energy protons are susceptible to self-absorption and result in the loss of enhancement observed for larger nanoparticles and thicker coatings. The radiolysis yield and dose increase with nanoparticle size however, the yield and dose per gold mass decrease due to self-absorption. Therefore, an intermediate nanoparticle size of approximately 10-25 nm maximizes both the radiolysis yield and dose as well as the enhancement. Coatings should be kept to the minimum effective thickness to limit the loss of enhancement. For molecular coatings such as PEG, coating density should be maximized as this increases the coating's effectiveness with only a minimal effect on enhancement.
Unhindered copper uptake by glutaraldehyde-polyethyleneimine coatings in an artificial seawater model system with adsorbed swollen polysaccharides and competing ligand EDTA
Publisher: Informa UK Limited
Date: 07-02-2017
DOI: 10.1080/08927014.2017.1284204
Abstract: Shortly after a surface is submerged in the sea, a conditioning film is generally formed by adsorption of organic molecules, such as polysaccharides. This could affect transport of molecules and ions between the seawater and the surface. An artificial seawater model system was developed to understand how adsorbed polysaccharides impact copper binding by glutaraldehyde-crosslinked polyethyleneimine coatings. Coating performance was also determined when competed against copper-chelating EDTA. Polysaccharide adsorption and copper binding and distribution were investigated using advanced analytical techniques, including depth-resolved time-of-flight secondary ion mass spectroscopy, grazing incidence X-ray absorption near-edge spectroscopy, quartz crystal microbalance with dissipation monitoring and X-ray photoelectron spectroscopy. In artificial seawater, the polysaccharides adsorbed in a swollen state that copper readily penetrated and the glutaraldehyde-polyethyleneimine coatings outcompeted EDTA for copper binding. Furthermore, the depth distribution of copper species was determined with nanometre precision. The results are highly relevant for copper-binding and copper-releasing materials in seawater.
Complete microscale profiling of tumor microangiogenesis A microradiological methodology reveals fundamental aspects of tumor angiogenesis and yields an array of quantitative parameters for its characterization
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.BIOTECHADV.2011.12.001
Abstract: Complete profiling would substantially facilitate the fundamental understanding of tumor angiogenesis and of possible anti-angiogenesis cancer treatments. We developed an integrated synchrotron-based methodology with excellent performances: detection of very small vessels by high spatial resolution (~1 μm) and nanoparticle contrast enhancement, in vivo dynamics investigations with high temporal resolution (~1 ms), and three-dimensional quantitative morphology parametrization by computer tracing. The smallest (3-10 μm) microvessels were found to constitute >80% of the tumor vasculature and exhibit many structural anomalies. Practical applications are presented, including vessel microanalysis in xenografted tumors, monitoring the effects of anti-angiogenetic agents and in vivo detection of tumor vascular rheological properties.
Penetration of zinc into human skin after topical application of nano zinc oxide used in commercial sunscreen formulations
Publisher: American Chemical Society (ACS)
Date: 19-05-2020
Abstract: Zinc oxide nanoparticles (ZnO NPs) are a key constituent of many commercial broad-spectrum sunscreens. Studies have shown that these NPs are retained on the superficial layers of the skins' barrier layer, the stratum corneum, and solubilized zinc species from the ZnO NPs have been shown qualitatively to penetrate intact human skin. The cytotoxicity of zinc is concentration- and species-dependent however, to date, the amount of zinc permeating the skin strata is yet to be determined. Here, we applied commercial ZnO NPs to intact and impaired
Extracellular delivery of modified oligonucleotide and superparamagnetic iron oxide nanoparticles from a degradable hydrogel triggered by tumor acidosis
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.BIOMATERIALS.2013.02.058
Abstract: Chemically modified antisense RNA oligonucleotides (antagomir) offer promise for cancer therapies but suffer from poor therapeutic effect after systemic administration. Chemical modification or loading in degradable hydrogels can offer improvements in the accuracy and efficacy for sustained delivery at specific sites. In our approach, antagomir were entrapped with degradable poly(ethylene glycol) (PEG)-based hydrogels, with and without incorporation of imidazole. Superparamagnetic iron oxide nanoparticles (SPION) were simultaneously loaded with intent for magnetic resonance imaging (MRI). The incorporation of imidazole into the PEG hydrogels led to a tunable-pH-response that dictated hydrogel swelling ratio and release rate of antagomir and SPION. As a result, the PEG-imidazole hydrogel swelling ratio and degradation over a 5 week period changed up to 734% and 149% as the pH dropped from 7.4 to 6.7, respectively. The swelling ratio of PEG-imidazole hydrogels was completely reversible over repeatable cycles of pH change. The stimuli-responsive behavior of PEG-imidazole hydrogels was used for the release of antagomir and SPION under conditions consistent with tumor acidosis. This manuscript demonstrates feasibility in designing tunable-pH-responsive hydrogels for loading multimodality therapeutic and contrast agents to enhance the bioactivity of chemically modified antisense RNA oligonucleotide and SPION for acidosis-related tumor therapy and MRI imaging applications.
Quantitative synchrotron X-ray fluorescence study of the penetration of transferrin-conjugated gold nanoparticles inside model tumour tissues
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4NR02100B
Abstract: Quantitative synchrotron X-ray fluorescence study of the penetration of transferrin-conjugated gold nanoparticles inside multicellular tumour spheroids.
Imaging the penetration and distribution of zinc and zinc species after topical application of zinc pyrithione to human skin
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.TAAP.2018.02.012
Abstract: Zinc pyrithione is an active component incorporated in an extensive range of topically applied commercial products that are used worldwide. Despite its prevalence, no published study has investigated the penetration of zinc from the zinc pyrithione complex into human skin. Zinc is crucial for healthy skin function however an elevated concentration of labile zinc is toxic outside a narrow concentration range. Synchrotron X-ray fluorescence microscopy in conjunction with X-ray absorption near edge structure spectroscopy was used to map the deposition of zinc, quantitate the amount of zinc within the skin and to identify a change in the chemical form of zinc after application. This study has demonstrated a ~3.8 fold increase in zinc concentration within the viable epidermis (VE) after 24 h topical application of zinc pyrithione that increased significantly by ~250 fold after 48 h when compared to control skin. Confocal microscopy using a labile zinc specific dye, ZinPyr-1, showed that zinc pyrithione disrupted the skin cells zinc homeostasis and significantly increased the intracellular zinc concentration leading to cell toxicity. Overall, this study demonstrates that topical application of zinc pyrithione formulations leads to an increase in zinc penetration in human skin, consequently, raising concerns for potential localised toxicity to occur.
ToF-SIMS analysis of elemental distributions in human hair
Publisher: Elsevier BV
Date: 02-2005
DOI: 10.1016/J.SCITOTENV.2004.07.017
Abstract: Elemental distributions on whole and longitudinal sections of hairs plucked from the scalp were studied with the surface sensitive technique time-of-flight secondary ion mass spectrometry (ToF-SIMS). Endogenous and environmental influences on the distributions of elemental species were identified. The cuticle scales appear to play the major role in the accumulation of exogenous products. The functionality of the outer surfaces and scale edges each preferentially bind different elemental species. The majority of elements considered accumulated longitudinally on the outer surface of the hair above the scalp level. Internally, most elemental signals (especially Al) decreased longitudinally once exposed to the environment with the exception of Si, which showed an increase. Images of elemental distributions within the medulla suggest that regions of different reactivity exist and show a variable ability to accumulate elemental species. The greatest signal intensities were observed in the cuticle and medulla regions rather than the cortex. The cuticle is continually exposed to environmental contamination and the medulla may, or may not, exist in a hair. Therefore, the components of a hair that potentially contribute the most to the elemental concentrations (i.e. the cuticle and medulla) are also the most variable, and as such greatly complicate the interpretation of elemental concentrations in hair. Results also suggest that bleaching hair can enhance the accumulation of contaminants.
Determination of Arsenic Poisoning and Metabolism in Hair by Synchrotron Radiation: The Case of Phar Lap
Publisher: Wiley
Date: 06-2010
Environment acidity triggers release of recombinant adeno-associated virus serotype 2 from a tunable matrix
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.JCONREL.2013.05.009
Abstract: Successful design of a pH responsive polyelectrolyte-based virus delivery matrix with extracellular release triggered by tumor acidosis has been achieved. Recombinant adeno-associated virus serotype 2 (AAV2) is loaded in the polyelectrolyte-based matrix (AAV2-matrix), which is formed by a biodegradable copolymer of poly(polyethylene glycol-1-(3-aminopropyl)imidazole-dl-aspartic acid) with tuned pH response based on inclusion of polyethyleneimine (PEI(800)). Physico-chemical properties of AAV2-matrix are optimized to minimize cellular interactions until a tumor acidosis-like environment protonates the matrix, reverses ζ-potential and causes particles to swell, releasing the AAV2 virus. The pH-dependent release is highly controllable and potentially useful to optimize site specific viral delivery.
Fate of Intravenously Administered Gold Nanoparticles in Hair Follicles: Follicular Delivery, Pharmacokinetic Interpretation, and Excretion
Publisher: Wiley
Date: 29-08-2012
Abstract: Gold nanoparticles (GNPs) are intravenously administered to mice. Deposition at the pilosebacious unit and whiskers is visualized with X-ray fluorescence after 30 minutes and 14 days. After 30 minutes the dermal papilla, bulge region, and root sheath all contain NPs. GNPs are driven externally out from follicles, counteractive to transfollicular delivery. After 14 days, gold bands in hairs reflect pharmacokinetic profiles indicating blood concentration kinetics. Elimination rate constants infer half-lives from 3 hairs from an in idual mouse within reasonable agreement (6.08, 7.15, and 8.66 hours). 3D reconstruction of NP distributions with confocal microscopy identifies aggregates within the medullary canal. Intermittent NP deposition continues randomly over the two week period demonstrating prolonged NP mobility in vivo. NPs are still retained at the hair bulb after 14 days. The observations further account for the excretory mechanisms of NPs and their behavior in the pilosebacous unit, and demonstrate monitoring pharmacokinetic behavior in in idual animals.
A quantitative study of intercellular heterogeneity in gold nanoparticle uptake across multiple cell lines
Publisher: Springer Science and Business Media LLC
Date: 11-2019
DOI: 10.1007/S00216-019-02154-W
Abstract: Quantification of intercellular heterogeneity in nanoparticle association is of paramount interest in research investigating applications of nanoparticles in the biomedical space. In this work, gold nanoparticle association (AuNP) in cell populations was quantified using synchrotron X-ray fluorescence microscopy (XRF) for 3 different cell lines (PC-3, Caco2 and MDA-MB-231) and 2 nanoparticle co-culture times (30 min and 10% of each respective cell lines' doubling time). Heterogeneity in association between single cells in the same population was dependant on cell line as well as co-culture time. AuNP association heterogeneity increased with co-culture time for 2 out of the 3 cell lines. Regardless of mean association quantity and measured intercellular heterogeneity, all data were best described by log normal distributions. Mean association between cell lines was statistically different at 30 min, yet indistinguishable at 10% doubling time. Heterogeneity between cell lines which demonstrated statistical differences in distribution can exist despite having statistically indistinguishable means.
Probing protein association with nano- and micro-scale structures with ToF-SIMS
Publisher: American Chemical Society
Date: 2012
Enhancement of cell radiation sensitivity by pegylated gold nanoparticles
Publisher: IOP Publishing
Date: 20-01-2010
DOI: 10.1088/0031-9155/55/4/002
Abstract: Biocompatible Au nanoparticles with surfaces modified by PEG (polyethylene glycol) were developed in view of possible applications for the enhancement of radiotherapy. Such nanoparticles exhibit preferential deposition at tumor sites due to the enhanced permeation and retention (EPR) effect. Here, we systematically studied their effects on EMT-6 and CT26 cell survival rates during irradiation for a dose up to 10 Gy with a commercial biological irradiator (E(average) = 73 keV), a Cu-Kalpha(1) x-ray source (8.048 keV), a monochromatized synchrotron source (6.5 keV), a radio-oncology linear accelerator (6 MeV) and a proton source (3 MeV). The percentage of surviving cells after irradiation was found to decrease by approximately 2-45% in the presence of PEG-Au nanoparticles ([Au] = 400, 500 or 1000 microM). The cell survival rates decreased as a function of the dose for all sources and nanoparticle concentrations. These results could open the way to more effective cancer irradiation therapies by using nanoparticles with optimized surface treatment. Difficulties in applying MTT assays were also brought to light, showing that this approach is not suitable for radiobiology.
Nanoparticle-Based Radiosensitization
Publisher: MDPI AG
Date: 29-04-2022
DOI: 10.3390/IJMS23094936
Abstract: Radiotherapy is a highly affordable treatment and provides many excellent outcomes [...]
Enhanced Targeting and Immune Activation of Tumor Microenvironment by Nanomodified Anti‐PD1 in Liver Cancer
Publisher: Wiley
Date: 16-04-2021
Abstract: Liver cancer is one of the most common cancers worldwide, 75% of which are hepatocellular carcinoma (HCC). Generally, chronic inflammation and an immunosuppressive tumor microenvironment are steadily activated in HCC. Although the US Food and Drug Administration (FDA) has approved immune checkpoint inhibitors (ICIs) for use as a clinically advanced HCC treatment, their efficacy in the clinical setting is not satisfactory. Moreover, only a small fraction of antibody reaches the target via systemic circulation due to neutralization of antibodies and off‐target delivery. To enhance the localized effects of ICIs, iron oxide nanoparticles (≈10 nm) are conjugated with an antiprogrammed death‐1 (anti‐PD1) antibody and introduced the ironized antibodies into orthotopic HCC tumors via the systemic circulation. When mice are sacrificed 13 days after the final treatment, mice treated with ironized anti‐PD1 significantly regulate tumor‐infiltrating leukocytes (TILs), particularly lifying T‐cell functions and recruiting M1 macrophages. More importantly, biochemical indices indicate that mice treated with ironized anti‐PD1 recover liver function. This work presents iron oxide nanoparticles integrated with an anti‐PD1 antibody that immunomodulates the immunosuppressive tumor microenvironment to generate synergistic effects that achieve tumor inhibition and immune response activation in the context of HCC therapy.
Imaging DNA double-strand breaks — are we there yet?
Publisher: Springer Science and Business Media LLC
Date: 04-07-2022
Correction to Magnetically Guided Viral Transduction of Gene-Based Sensitization for Localized Photodynamic Therapy To Overcome Multidrug Resistance in Breast Cancer Cells.
Publisher: American Chemical Society (ACS)
Date: 29-05-2018
Shape-Controlled Synthesis of Silver Nanocrystals by X-ray Irradiation for Inkjet Printing
Publisher: American Chemical Society (ACS)
Date: 29-10-2012
DOI: 10.1021/AM3015718
Abstract: A suite of silver (Ag) nanocrystals have been synthesized using a rapid water radiolysis approach via X-ray irradiation. Various shapes including spheroidal, prism, rod, and multifaceted nanoparticles can be produced by varying the initial concentration of polyvinylpyrrolidone (PVP) relative to silver nitrate (AgNO₃). UV-visible spectroscopy and transmission electron microscopy (TEM) coupled with selected area electron diffraction (SAED) have been used to characterize these Ag products. At an optimized reagent ratio, a mixture of high-aspect-ratio rods (tunable to ∼50) and spheroidal particles result. Such a mixture is proven to have highly beneficial melting point and dispersive properties suited to inkjet printing of conductive Ag lines. The resistivity of the printed lines decreases to 77.7 μΩ and 33.1 μΩ after heating to 200 and 350 °C.
Relating intercellular variability in nanoparticle uptake with biological consequence: a quantitative x-ray fluorescence study for radiosensitization of cells
Publisher: American Chemical Society (ACS)
Date: 16-10-2015
DOI: 10.1021/ACS.ANALCHEM.5B03183
Abstract: Internalized gold nanoparticles were quantified in large numbers of in idual prostate cancer cells using large area synchrotron X-ray fluorescence microscopy. Cells were also irradiated with a 6 MV linear accelerator to assess the biological consequence of radiosensitization with gold nanoparticles. A large degree of heterogeneity in nanoparticle uptake between cells resulted in influenced biological effect.
An acid degradable, lactate oxidizing nanoparticle formulation for non-small cell lung cancer virotherapy
Publisher: Elsevier BV
Date: 10-2022
Potential targeting of the tumor microenvironment to improve cancer virotherapy
Publisher: Elsevier BV
Date: 10-2023
Full-field microimaging with 8 keV X-rays achieves a spatial resolutions better than 20 nm
Publisher: The Optical Society
Date: 27-09-2011
DOI: 10.1364/OE.19.019919
CHANGES IN THE METAL CONTENT OF HUMAN HAIR DURING DIAGENESIS FROM 500 YEARS, EXPOSURE TO GLACIAL AND AQUEOUS ENVIRONMENTS
Publisher: Wiley
Date: 05-05-2010
Predictive modeling of hypoxic head and neck cancers during fractionated radiotherapy with gold nanoparticle radiosensitization
Publisher: Wiley
Date: 29-04-2021
DOI: 10.1002/MP.14872
Abstract: Intrinsic radioresistance and increased proliferation rates in head and neck cancers (HNCs) are associated with negative radiotherapy (RT) treatment responses. The use of gold nanoparticles (AuNPs) as radiosensitizers could enable total radiation dose reduction and lowered radiation toxicity. AuNP radiosensitization may overcome hypoxia‐induced radioresistance and treatment‐induced accelerated repopulation of cancer cells in HNCs, improving radiotherapy outcomes. Tumor control was determined by considering in idual cancer cell responses in probabilistic computational simulations using HYP‐RT software for clinical radiotherapy doses and fractionation schedules along with three different nanoparticle administration schedules. Antagonistic tumor hypoxia and rapid tumor regrowth due to accelerated repopulation of cancers cells were taken into consideration. Simulations indicate that tumors that are conventionally uncontrollable can be controlled with AuNP radiosensitization. In simulations where the absence of AuNPs required radiotherapy doses above standard clinical prescriptions, reoccurring AuNP administration allowed for radiation dose reductions below standard clinical dose prescriptions. For ex le, considering a 2 Gy per fraction radiotherapy schedule, tumor control was achieved with 57.2 ± 5.1 Gy ( P = .0001) for weekly AuNP administration and 53.0 ± 4.0 Gy ( P = .0001) for biweekly AuNP administration compared to 69.9 ± 5.8 Gy with no radiosensitization. AuNPs decreased the predicted RT total doses required to achieve tumor control via total stem cell elimination, offering an optimistic prediction and method for which hypoxia‐induced and rapidly growing radioresistant tumors are treated more effectively. Outcomes are also shown to be sensitive to the RT schedule with data for hyperfractionated RT indicating the greatest benefits from radiosensitization.
Aluminium Nanoparticles as Efficient Adjuvants Compared to Their Microparticle Counterparts: Current Progress and Perspectives
Publisher: MDPI AG
Date: 24-04-2022
DOI: 10.3390/IJMS23094707
Abstract: Aluminium (Al) compounds are used as adjuvants in human and veterinary prophylactic vaccines due to their improved tolerability compared to other adjuvants. These Al-based adjuvants form microparticles (MPs) of heterogeneous sizes ranging from ~0.5 to 10 µm and generally induce type 2 (Th2)-biased immune responses. However, recent literature indicates that moving from micron dimension particles toward the nanoscale can modify the adjuvanticity of Al towards type 1 (Th1) responses, which can potentially be exploited for the development of vaccines for which Th1 immunity is crucial. Specifically, in the context of cancer treatments, Al nanoparticles (Al-NPs) can induce a more balanced (Th1/Th2), robust, and durable immune response associated with an increased number of cytotoxic T cells compared to Al-MPs, which are more favourable for stimulating an oncolytic response. In this review, we compare the adjuvant properties of Al-NPs to those of Al-MPs in the context of infectious disease vaccines and cancer immunotherapy and provide perspectives for future research.
Preliminary synchrotron analysis of lead in hair from a lead smelter worker
Publisher: Elsevier BV
Date: 03-2005
DOI: 10.1016/J.CHEMOSPHERE.2004.09.087
Abstract: Synchrotron X-ray fluorescence has been used to study the distribution of lead in a hair s le collected from a lead smelter worker. A mathematical model was used to imitate the transverse scan signal based on the analysis volume and concentration profiles. The results suggest that the Pb originates both from ingestion and environmental exposure, however direct deposition from the environment is the more important source of hair lead. The model could apply equally to any other analysis involving a thin cylindrical s le.
Mass spectrometry imaging of pharmaceuticals: from tablets to tissues
Publisher: Springer New York
Date: 2016
Kinetic effects of transferrin-conjugated gold nanoparticles on the antioxidant glutathione-thioredoxin pathway
Publisher: MDPI AG
Date: 15-08-2023
Abstract: Nanoparticle-based therapeutics are being clinically translated for treating cancer. Even when thought to be biocompatible, nanoparticles are being increasingly identified as altering cell regulation and homeostasis. Antioxidant pathways are important for maintaining cell redox homeostasis and play important roles by maintaining ROS levels within tolerable ranges. Here, we sought to understand how a model of a relatively inert nanoparticle without any therapeutic agent itself could antagonize a cancer cell lines’ antioxidant mechanism. A label-free protein expression approach was used to assess the glutathione-thioredoxin antioxidative pathway in a prostate cancer cell line (PC-3) after exposure to gold nanoparticles conjugated with a targeting moiety (transferrin). The impact of the nanoparticles was also corroborated through morphological analysis with TEM and classification of pro-apoptotic cells by way of the sub-G0/G1 population via the cell cycle and annexin V apoptosis assay. After a two-hour exposure to nanoparticles, major proteins associated with the glutathione-thioredoxin antioxidant pathway were downregulated. However, this response was acute, and in terms of protein expression, cells quickly recovered within 24 h once nanoparticle exposure ceased. The impact on PRDX-family proteins appears as the most influential factor in how these nanoparticles induced an oxidative stress response in the PC-3 cells. An apparent adaptive response was observed if exposure to nanoparticles continued. Acute exposure was observed to have a detrimental effect on cell viability compared to continuously exposed cells. Nanoparticle effects on cell regulation likely provide a compounding therapeutic advantage under some circumstances, in addition to the action of any cytotoxic agents however, any therapeutic advantage offered by nanoparticles themselves with regard to vulnerabilities specific to the glutathione-thioredoxin antioxidative pathway is highly temporal.
In Vivo–in Vitro and XANES Spectroscopy Assessments of Lead Bioavailability in Contaminated Periurban Soils
Publisher: American Chemical Society (ACS)
Date: 28-06-2011
DOI: 10.1021/ES200653K
Abstract: Lead (Pb) bioaccessibility was assessed using 2 in vitro methods in 12 Pb-contaminated soils and compared to relative Pb bioavailability using an in vivo mouse model. In vitro Pb bioaccessibility, determined using the intestinal phase of the Solubility Bioaccessibility Research Consortium (SBRC) assay, strongly correlated with in vivo relative Pb bioavailability (R(2) = 0.88) following adjustment of Pb dissolution in the intestinal phase with the solubility of Pb acetate at pH 6.5 (i.e., relative Pb bioaccessibility). A strong correlation (R(2) = 0.78) was also observed for the relative bioaccessibility leaching procedure (RBALP), although the method overpredicted in vivo relative Pb bioavailability for soils where values were <40%. Statistical analysis of fit results from X-ray absorption near-edge structure (XANES) data for selected soils (n = 3) showed that Pb was strongly associated with Fe oxyhydroxide minerals or the soil organic fraction prior to in vitro analysis. XANES analysis of Pb speciation during the in vitro procedure demonstrated that Pb associated with Fe minerals and the organic fraction was predominantly solubilized in the gastric phase. However, during the intestinal phase of the in vitro procedure, Pb was strongly associated with formation of ferrihydrite which precipitated due to the pH (6.5) of the SBRC intestinal phase. Soils where Fe dissolution was limited had markedly higher concentrations of Pb in solution and hence exhibited greater relative bioavailability in the mouse model. This data suggests that coexistence of Fe in the intestinal phase plays an important role in reducing Pb bioaccessibility and relative bioavailability.
Bio-template assisted synthesis of porous glutaraldehyde-polyethyleneimine particulate resin for selective copper ion binding and recovery
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8RA00454D
Abstract: Porous ion-exchange resins with features of high selectivity, high capacity, fast adsorption kinetics and chemical stability over a wide pH range are attractive for extracting precious metals like copper and upcycling waste.
Applications of synchrotron radiation in forensic trace evidence analysis
Publisher: Elsevier BV
Date: 15-08-2005
Light-triggered methylcellulose gold nanoparticle hydrogels for leptin release to inhibit fat stores in adipocytes
Publisher: Informa UK Limited
Date: 10-2017
DOI: 10.2147/IJN.S144986
Remote Control of Light-Triggered Virotherapy
Publisher: American Chemical Society (ACS)
Date: 07-11-2016
Abstract: Clinical virotherapy has been successfully approved for use in cancer treatment by the U.S. Food and Drug Administration however, a number of improvements are still sought to more broadly develop virotherapy. A particular challenge is to administer viral therapy systemically and overcome limitations in intratumoral injection, especially for complex tumors within sensitive organs. To achieve this, however, a technique is required that delivers the virus to the tumor before the body's natural self-defense eradicates the virus prematurely. Here we show that recombinant adeno-associated virus serotype 2 (AAV2) chemically conjugated with iron oxide nanoparticles (∼5 nm) has a remarkable ability to be remotely guided under a magnetic field. Transduction is achieved with microscale precision. Furthermore, a gene for production of the photosensitive protein KillerRed was introduced into the AAV2 genome to enable photodynamic therapy (PDT), or light-triggered virotherapy. In vivo experiments revealed that magnetic guidance of "ironized" AAV2-KillerRed injected by tail vein in conjunction with PDT significantly decreases the tumor growth via apoptosis. This proof-of-principle demonstrates guided and highly localized microscale, light-triggered virotherapy.
An image processing application for quantitative cross-correlative microscopy for large cell-populations: a gold nanoparticle radiosensitisation study
Publisher: Cambridge University Press (CUP)
Date: 02-08-2017
DOI: 10.1017/S0885715617000719
Abstract: A robust analysis script was developed in MATLAB for cross-correlative quantification of internalised gold nanoparticle (AuNP) uptake in a large number of in idual cells with the corresponding number of DNA double-strand breaks (DSBs) in the same cells. The correlation of inorganic NP content with a biological marker at the single-cell level will aid in the elucidation of mechanisms of NP radiosensitisation. PC-3 cells were co-cultured with AuNPs and irradiated using an iridium-192 source. AuNP uptake was measured using synchrotron X-ray fluorescence (XRF) and DSBs imaged via confocal microscopy. MATLAB 2016a was used to develop a script to cross-correlate the two imaging modalities and quantify both DSBs and internalised AuNP content in the same cell. Various user-defined options written into the script give a high degree of versatility, which can account for a large number of variables in experimental parameters and data acquisition. The analysis procedure is flexible and robust, which gives consistent consideration to the wide spectrum of potential input image/data sets. Quantitative correlative microscopy was achieved with a custom MATLAB script used to correlate γH2AX foci (a marker of DNA DSBs) from confocal microscopy with AuNP content acquired using synchrotron XRF at the single-cell level. The script can be extended to a broad range of multi-modality imaging spectroscopies.
Switchable delivery of small interfering RNA using a negatively charged pH-responsive polyethylenimine-based polyelectrolyte complex
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3CC00134B
Abstract: A small interfering RNA (siRNA)-loaded polyelectrolyte constructed with branched polyethylenimine (bPEI) and copolymers, consisting of polyethylene glycol (PEG), histidine (His), and glutamic acid (Glu), was developed in order to provide a tumor acidosis-triggered delivery system with low cytotoxicity.
Orientating lipase molecules through surface chemical control for enhanced activity: a QCM-D and ToF-SIMS investigation
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.COLSURFB.2016.02.059
Abstract: Bio-active materials consisting of lipase encapsulated within porous silica particles were engineered to control the adsorption kinetics and molecular orientation of lipase, which play critical roles in the digestion kinetics of triglycerides. The adsorption kinetics of Candida antartica lipase A (CalA) was monitored using quartz crystal microbalance with dissipation (QCM-D) and controlled by altering the hydrophobicity of a silica binding support. The extent of adsorption was 2-fold greater when CalA was adsorbed onto hydrophobic silica compared to hydrophilic silica. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) fragmentation patterns, in conjunction with multivariate statistics, demonstrated enhanced exposure of the lipase's catalytic domain, specifically the histidine group responsible for activity, when CalA was adsorbed on hydrophilic silica. Consequently, lipid digestion kinetics were enhanced when CalA was loaded in hydrophilic porous silica particles, i.e., a 2-fold increase in the pseudo-first-order rate constant for digestion when compared to free lipase. In contrast, digestion kinetics were inhibited when CalA was hosted in hydrophobic porous silica, i.e., a 5-fold decrease in pseudo-first-order rate constant for digestion when compared to free lipase. These findings provide valuable insights into the mechanism of lipase action which can be exploited to develop smarter food and drug delivery systems consisting of porous lipid-based materials.
Peptide and protein loading into porous silicon wafers
Publisher: Wiley
Date: 02-2008
Organic and inorganic discrimination of ballpoint pen inks by ToF-SIMS and multivariate statistics
Publisher: Elsevier BV
Date: 2010
Cell size as a primary determinant in targeted nanoparticle uptake
Publisher: American Chemical Society (ACS)
Date: 26-08-2022
Dressing in Layers: Layering Surface Functionalities in Nanoporous Aluminum Oxide Membranes
Publisher: Wiley
Date: 15-09-2010
One-Pot Tuning of Au Nucleation and Growth: From Nanoclusters to Nanoparticles
Publisher: American Chemical Society (ACS)
Date: 06-2011
DOI: 10.1021/LA200861E
Abstract: 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.
Characterizing arsenic in preserved hair for assessing exposure potential and discriminating poisoning
Publisher: International Union of Crystallography (IUCr)
Date: 27-03-2009
Cross-correlative single-cell analysis reveals biological mechanisms of nanoparticle radiosensitization
Publisher: American Chemical Society (ACS)
Date: 22-04-2019
Modelling Spatial Scales of Dose Deposition and Radiolysis Products from Gold Nanoparticle Sensitisation of Proton Therapy in A Cell: From Intracellular Structures to Adjacent Cells
Publisher: MDPI AG
Date: 22-06-2020
DOI: 10.3390/IJMS21124431
Abstract: Gold nanoparticle (GNP) enhanced proton therapy is a promising treatment concept offering increased therapeutic effect. It has been demonstrated in experiments which provided indications that reactive species play a major role. Simulations of the radiolysis yield from GNPs within a cell model were performed using the Geant4 toolkit. The effect of GNP cluster size, distribution and number, cell and nuclear membrane absorption and intercellular yields were evaluated. It was found that clusters distributed near the nucleus increased the nucleus yield by 91% while reducing the cytoplasm yield by 7% relative to a disperse distribution. Smaller cluster sizes increased the yield, 200 nm clusters had nucleus and cytoplasm yields 117% and 35% greater than 500 nm clusters. Nuclear membrane absorption reduced the cytoplasm and nucleus yields by 8% and 35% respectively to a permeable membrane. Intercellular enhancement was negligible. Smaller GNP clusters delivered near sub-cellular targets maximise radiosensitisation. Nuclear membrane absorption reduces the nucleus yield, but can damage the membrane providing another potential pathway for biological effect. The minimal effect on adjacent cells demonstrates that GNPs provide a targeted enhancement for proton therapy, only effecting cells with GNPs internalised. The provided quantitative data will aid further experiments and clinical trials.
Validation of a Vasculogenesis Microfluidic Model for Radiobiological Studies of the Human Microvasculature
Publisher: Wiley
Date: 07-03-2019
Gold nanoparticle enhanced proton therapy: Monte carlo modeling of reactive species' distributions around a gold nanoparticle and the effects of nanoparticle proximity and clustering
Publisher: MDPI AG
Date: 09-2019
DOI: 10.3390/IJMS20174280
Abstract: Gold nanoparticles (GNPs) are promising radiosensitizers with the potential to enhance radiotherapy. Experiments have shown GNP enhancement of proton therapy and indicated that chemical damage by reactive species plays a major role. Simulations of the distribution and yield of reactive species from 10 ps to 1 µs produced by a single GNP, two GNPs in proximity and a GNP cluster irradiated with a proton beam were performed using the Geant4 Monte Carlo toolkit. It was found that the reactive species distribution at 1 µs extended a few hundred nm from a GNP and that the largest enhancement occurred over 50 nm from the nanoparticle. Additionally, the yield for two GNPs in proximity and a GNP cluster was reduced by up to 17% and 60% respectively from increased absorption. The extended range of action from the diffusion of the reactive species may enable simulations to model GNP enhanced proton therapy. The high levels of absorption for a large GNP cluster suggest that smaller clusters and diffuse GNP distributions maximize the total radiolysis yield within a cell. However, this must be balanced against the high local yields near a cluster particularly if the cluster is located adjacent to a biological target.
X-ray synthesized PEGylated (polyethylene glycol coated) gold nanoparticles in mice strongly accumulate in tumors
Publisher: Elsevier BV
Date: 03-2011
Mechanisms of nanoparticle radiosensitization
Publisher: Wiley
Date: 19-07-2020
DOI: 10.1002/WNAN.1656
Abstract: Metal‐based nanoparticles applied to potentiating the effects of radiotherapy have drawn significant attention from the research community and are now available clinically. By improving our mechanistic understanding, nanoparticles are likely to evolve to provide very significant improvements in radiotherapy outcomes with only incremental increase in cost. This review critically assesses the inconsistent observations surrounding physical, physicochemical, chemical and biological mechanisms of radiosensitization. In doing so, a number of needs are identified for continuing research and are highlighted. The large degree of variability from one nanoparticle to another emphasizes that it is a mistake to generalize nanoparticle radiosensitizer mechanisms. Nanoparticle formulations should be considered in an analogous way as pharmacological agents and as a broad class of therapeutic agents, needing to be considered with a high degree of in iduality with respect to their interactions and ultimate impact on radiobiological response. In the same way that no universal anti‐cancer drug exists, it is unlikely that a single nanoparticle formulation will lead to the best therapeutic outcomes for all cancers. The high degree of complexity and variability in mechanistic action provides notable opportunities for nanoparticle formulations to be optimized for specific indications. This article is categorized under: Therapeutic Approaches and Drug Discovery Emerging Technologies Nanotechnology Approaches to Biology Nanoscale Systems in Biology
Targeting non-apoptotic cell death in cancer treatment by nanomaterials: Recent advances and future outlook
Publisher: Elsevier BV
Date: 10-2020
Large area synchrotron X-ray fluorescence mapping of biological samples
Publisher: IOP Publishing
Date: 17-12-2014
Cu(In1−xGax)S2 nanocrystals and films: low-temperature synthesis with size and composition control
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3NR00264K
Abstract: We demonstrate a single-step X-ray irradiation process that yields high-quality Cu(In1-xGax)S2 nanocrystals in colloidal solutions, with complete control of size and composition. Thin films produced by drop-casting exhibit high-quality photoresponse, confirming that our process is suitable for microelectronics applications.
Fabrication of single crystal CuGaS2 nanorods by X-ray irradiation
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C1CC12031J
Abstract: CuGaS(2) nanorods were synthesized by irradiating the precursor solution with intense X-rays. The products are single crystal nanorods with preferential [220] growth and a uniform size distribution. We also report on the photoresponse of drop-cast films of these nanorods.
Restructuring and Remodeling of NaREF4 Nanocrystals by Electron Irradiation
Publisher: Wiley
Date: 20-06-2014
Abstract: NaREF4 nanocrystals are found to be highly manipulable by electron beam irradiation. With 200 kV electron beam irradiation, both 14.6 nm spherical NaGdF4 :Yb,Er nanoparticles and 44.7 nm × 34.1 nm ellipsoidal NaYF4 :Yb,Er nanorods form hollow structures and eventually convert to the corresponding REF3 upon prolonged irradiation. Furthermore, the NaYF4 nanorods fractured with irradiation with a 100 kV electron source are found to be subsequently self-healed when irradiated with a 200 kV source. The detailed experimental results, in combination with theoretical analysis, suggest that knock-on effects, specific lattice energy, and the inherently low surface energy of NaREF4 collectively contribute to the formation of the hollow structures. These mechanisms allow controlled engineering and manipulation of RE nanomaterials on the nanometer scale.
Formulation of simvastatin within high density lipoprotein enables potent tumour radiosensitisation
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.JCONREL.2022.04.017
Abstract: Preclinical, clinical and epidemiologic studies have established the potent anticancer and radiosensitisation effects of HMG-CoA reductase inhibitors (statins). However, the low bioavailability of oral statin formulations is a key barrier to achieving effective doses within tumour. To address this issue and ascertain the radiosensitisation potential of simvastatin, we developed a parenteral high density lipoprotein nanoparticle (HDL NP) formulation of this commonly used statin. A scalable method for the preparation of the simvastatin-HDL NPs was developed using a 3D printed microfluidic mixer. This enables the production of litre scale amounts of particles with minimal batch to batch variation. Simvastatin-HDL NPs enhanced the radiobiological response in 2D/3D head and neck squamous cell carcinoma (HNSCC) in vitro models. The simvastatin-HDL NPs radiosensitisation was comparable to that of 10 and 5 times higher doses of free drug in 2D and 3D cultures, respectively, which could be partially explained by more efficient cellular uptake of the statin in the nanoformulation as well as by the inherent biological activity of the HDL NPs on the cholesterol pathway. The radiosensitising potency of the simvastatin-HDL nanoformulation was validated in an immunocompetent MOC-1 HNSCC tumour bearing mouse model. This data supports the rationale of repurposing statins through reformulation within HDL NPs. Statins are safe and readily available molecules including as generic, and their use as radiosensitisers could lead to much needed effective and affordable approaches to improve treatment of solid tumours.
Advanced analysis of metal distributions in human hair
Publisher: American Chemical Society (ACS)
Date: 18-04-2006
DOI: 10.1021/ES052158V
Abstract: A variety of techniques (secondary electron microscopy with energy dispersive X-ray analysis, time-of-flight--secondary ion mass spectrometry, and synchrotron X-ray fluorescence) were utilized to distinguish metal contamination occurring in hair arising from endogenous uptake from an in idual exposed to a polluted environment, in this case a lead smelter. Evidence was sought for elements less affected by contamination and potentially indicative of biogenic activity. The unique combination of surface sensitivity, spatial resolution, and detection limits used here has provided new insight regarding hair analysis. Metals such as Ca, Fe, and Pb appeared to have little representative value of endogenous uptake and were mainly due to contamination. Cu and Zn, however, demonstrate behaviors worthy of further investigation into relating hair concentrations to endogenous function.
Discrimination of pencil markings on paper using elemental analysis: An initial investigation
Publisher: Elsevier BV
Date: 03-2008
DOI: 10.1016/J.FORSCIINT.2007.05.017
Abstract: The characterisation and comparison of pencil markings on paper is an area of questioned document analysis that has previously not received much attention. Despite this, there would be value in an examiner being able to analyse two pencil markings and coming to a conclusion about whether they were from a similar or different source. Previous studies have analysed raw materials and bulk pencil cores for purposes of characterisation and differentiation, but to date, no studies have successfully analysed pencil markings non-destructively off a paper substrate. In this work, pencils from a number of manufacturers were analysed by inductively coupled plasma mass spectrometry (ICP-MS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Analysis of data using multivariate techniques (principal component analysis), showed that ToF-SIMS can successfully be used to analyse such pencil markings to deduce whether two markings can be differentiated, in terms of inorganic elemental composition. It was possible to discriminate between pencil markings from different manufacturers, and it was also indicated that pencils from the same manufacturer, but discrete batches, can be significantly different.
Localization and speciation of arsenic and trace elements in rice tissues
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.CHEMOSPHERE.2009.03.010
Abstract: The consumption of arsenic (As) contaminated rice is an important exposure route for humans in countries where rice cultivation employs As contaminated irrigation water. Arsenic toxicity and mobility are a function of its chemical-speciation. The distribution and identification of As in the rice plant are hence necessary to determine the uptake, transformation and potential risk posed by As contaminated rice. In this study we report on the distribution and chemical-speciation of As in rice (Oryza sativa Quest) by X-ray fluorescence (XRF) and X-ray absorption near edge structure (XANES) measurements of rice plants grown in As contaminated paddy water. Investigations of muXRF images from rice tissues found that As was present in all rice tissues, and its presence correlated with the presence of iron at the root surface and copper in the rice leaf. X-ray absorption near edge structure analysis of rice tissues identified that inorganic As was the predominant form of As in all rice tissues studied, and that arsenite became increasingly dominant in the aerial portion of the rice plant.
Micro‐scale RNA Interference using Iron Oxide Nanoparticle‐modified Lentivirus
Publisher: Wiley
Date: 25-10-2017
Highly specific in vivo gene delivery for p53-mediated apoptosis and genetic photodynamic therapies of tumour
Publisher: Springer Science and Business Media LLC
Date: 05-03-2015
DOI: 10.1038/NCOMMS7456
Abstract: Anticancer therapies are often compromised by nonspecific effects and challenged by tumour environments’ inherent physicochemical and biological characteristics. Often, therapeutic effect can be increased by addressing multiple parameters simultaneously. Here we report on exploiting extravasation due to inherent vascular leakiness for the delivery of a pH-sensitive polymer carrier. Tumours’ acidic microenvironment instigates a charge reversal that promotes cellular internalization where endosomes destabilize and gene delivery is achieved. We assess our carrier with an aggressive non-small cell lung carcinoma (NSCLC) in vivo model and achieve % transfection efficiency via systemic delivery. Rejuvenation of the p53 apoptotic pathway as well as expression of KillerRed protein for sensitization in photodynamic therapy (PDT) is accomplished. A single administration greatly suppresses tumour growth and extends median animal survival from 28 days in control subjects to 68 days. The carrier has capacity for multiple payloads for greater therapeutic response where inter-in idual variability can compromise efficacy.
Validation and investigation of reactive species yields of Geant4-DNA chemistry models
Publisher: Wiley
Date: 26-12-2019
DOI: 10.1002/MP.13332
Abstract: Indirect biological damage due to reactive species produced in water radiolysis reactions is responsible for the majority of biological effect for low linear energy transfer (LET) radiation. Modeling water radiolysis and the subsequent interactions of reactive species, as well as track structures, is essential to model radiobiology on the microscale. Recently, chemistry models have been developed for Geant4-DNA to be used in combination with the comprehensive existing physics models. In the current work, the first detailed, independent, in silico validation of all species yields with published experimental observations and comparison with other radiobiological simulations is presented. Additionally, the effect of LET of protons and heavier ions on reactive species yield in the model was examined, as well as the completeness of the chemical reactions following the radiolysis within the time after physical interactions simulated in the model. Yields over time of reactive species were simulated for water radiolysis by incident electrons, protons, alpha particles, and ions with various LETs using Geant4 and RITRACKS simulation tools. Water dissociation and recombination was simulated using Geant4 to determine the completeness of chemical reactions at the end of the simulation. Yield validation was performed by comparing yields simulated using Geant4 with experimental observations and other simulations. Validation was performed for all species for low LET radiation and the solvated electron and hydroxyl radical for high LET ions. It was found that the Geant4-DNA chemistry yields were generally in good agreement with experimental observations and other simulations. However, the Geant4-DNA yields for the hydroxyl radical and hydrogen peroxide at the end of the chemistry stage were found to be respectively considerably higher and lower than the experimentally observed yields. Increasing the LET of incident hadrons increased the yield of secondary species and decreased the yield of primary species. The effect of LET on the yield of the hydroxyl radical at 100 ns simulated with Geant4 was in good agreement with experimental measurements. Additionally, by the end of the simulation only 40% of dissociated water molecules had been recombined and the rate of recombination was slowing. The yields simulated using Geant4 are within reasonable agreement with experimental observations. Higher LET radiation corresponds with increased yields of secondary species and decreased yields of primary species. These trends combined with the LET having similar effects on the 100 ns hydroxyl radical yield for Geant4 and experimental measurements indicate that Geant4 accurately models the effect of LET on radiolysis yields. The limited recombination within the modeled chemistry stage and the slowing rate of recombination at the end of the stage indicate potential long-range indirect biological damage.
Controlling the surface functionalities of nanoporous alumina membranes
Publisher: IEEE
Date: 02-2010
Controlled delivery of recombinant adeno-associated virus serotype 2 using pH-sensitive poly(ethylene glycol)-poly-l-histidine hydrogels
Publisher: Elsevier BV
Date: 12-2012
DOI: 10.1016/J.BIOMATERIALS.2012.09.018
Abstract: Loading of viral vectors in synthetic polymers is a promising strategy for overcoming hurdles associated with viral gene delivery. For enhanced gene expression at a specific site, gene transfer by using hydrogels represents a versatile approach. In this study, adeno-associated virus serotype 2 containing the green fluorescent protein gene (rAAV2-GFP) were loaded into poly(ethylene glycol) (PEG) hydrogels, with and without incorporation of poly-L-hisditine (polyHis). Inclusion of polyHis created pH responsive hydrogels in a physiological range of tissues, containing the damaged vasculature and activated phagocytosis. The fraction of polyHis used controlled the degree of swelling, water uptake and subsequent degradation of the hydrogels and release rate of rAAV2-GFP. The swelling ratio of the PEG-polyHis hydrogels increased inversely with environment pH. As pH declined from 7.4 to 6.0, PEG-polyHis hydrogel swelling ratio and degradation rate increased 875% and 135%, respectively. As a result, release and transduction efficiency of the rAAV2-GFP from PEG-polyHis hydrogel in human HT-1080 fibrosarcoma cells increased significantly compared to a PEG hydrogel. Transduction rate can be controlled by the hydrogels' polyHis concentration and is sensitive to localized decreases in pH consistent with inflammation. This is relevant to optimizing parameters for wound care and regenerative medicine applications.
Time-of-flight secondary ion mass spectrometry analysis of hair from archaeological remains
Publisher: SAGE Publications
Date: 12-2003
DOI: 10.1255/EJMS.584
Abstract: Hair from four in iduals excavated from burial sites in Pacatnamu, Peru from the Moche (450–800 AD) and Lambayeque (900–1100 AD) periods was sectioned longitudinally and analysed with time-of-flight secondary ion mass spectrometry (ToF-SIMS). An attempt was made to distinguish biogenic and diagenetic contributions to the elemental concentrations in the hair s les. Significant contamination was observed to have penetrated the hair s les from the burial environment. Results from the analyses indicate that the burial environment plays an important role in the postmortem variation in elemental content of hair s les. Various elements demonstrated an ability to permeate through the hair matrix over time. In addition, NaCl and what are believed to be aluminosilicates and mineral sulphates, were observed to have accumulated on the surface of the s les. Degradation of the s les was also suspected due to the presence of molecular fragments, possibly resulting from oxidation of the keratin proteins. The results should assist in the identification of reliable elemental signals in the analysis of ancient hair s les and promote caution when considering elements that are abundant in the burial environment.
Magnetically Engineered Semiconductor Quantum Dots as Multimodal Imaging Probes
Publisher: Wiley
Date: 09-2014
Abstract: Light-emitting semiconductor quantum dots (QDs) combined with magnetic resonance imaging contrast agents within a single nanoparticle platform are considered to perform as multimodal imaging probes in biomedical research and related clinical applications. The principles of their rational design are outlined and contemporary synthetic strategies are reviewed (heterocrystalline growth co-encapsulation or assembly of preformed QDs and magnetic nanoparticles conjugation of magnetic chelates onto QDs and doping of QDs with transition metal ions), identifying the strengths and weaknesses of different approaches. Some of the opportunities and benefits that arise through in vivo imaging using these dual-mode probes are highlighted where tumor location and delineation is demonstrated in both MRI and fluorescence modality. Work on the toxicological assessments of QD/magnetic nanoparticles is also reviewed, along with progress in reducing their toxicological side effects for eventual clinical use. The review concludes with an outlook for future biomedical imaging and the identification of key challenges in reaching clinical applications.
Detecting the presence of denatured human serum albumin in an adsorbed protein monolayer using TOF-SIMS
Publisher: American Chemical Society (ACS)
Date: 08-06-2010
DOI: 10.1021/LA101253G
Abstract: We demonstrate the application of time-of-flight secondary ion mass spectrometry (TOF-SIMS) in conjunction with multivariate statistics to differentiate trace levels of denatured proteins in adsorbed monolayers specifically, human serum albumin (HSA) on oxidized silicon substrates. Subtle differences in protein conformation due to thermal denaturation of HSA, unable to be determined by dynamic light scattering nor circular dichroism, were differentiated by TOF-SIMS. The fragmentation pattern is highly sensitive to protein conformation, allowing assessment of relative amounts of proteins in mixtures and quantifying amounts of denatured protein in a s le. Discussion is presented on ascribing orientation and conformational differences between s les based upon TOF-SIMS spectra. This has implications for detecting denatured protein in biotechnology and medical applications.
Hard x-ray Zernike microscopy reaches 30 nm resolution
Publisher: The Optical Society
Date: 30-03-2011
DOI: 10.1364/OL.36.001269
Environmental copper sensor based on polyethylenimine-functionalized nanoporous anodic alumina interferometers
Publisher: American Chemical Society (ACS)
Date: 22-02-2019
Targeting Tumor Microenvironment by Bioreduction-Activated Nanoparticles for Light-Triggered Virotherapy.
Publisher: American Chemical Society (ACS)
Date: 02-10-2018
Abstract: Solid tumors characteristically display higher levels of lactate production due to anaerobic metabolism of glucose. Meanwhile, the U.S. Food and Drug Administration (FDA) has approved virotherapy for use in cancer treatment however systemic administration remains as a particular challenge. Here we report exploitation of tumor lactate production in designing a hypoxia-responsive carrier, self-assembled from hyaluronic acid (HA) conjugated with 6-(2-nitroimidazole)hexylamine, for localized release of recombinant adeno-associated virus serotype 2 (AAV2). The carrier is loaded with lactate oxidase (LOX) and is permeable to small molecules such as the lactate that accumulates in the tumor. Subsequently, LOX oxidizes the lactate to pyruvate inside the carrier, accompanied by internal lowering of oxygen partial pressure. Bioreduction of the 2-nitroimidazole of the HA conjugated with 6-(2-nitroimidazole)hexylamine converts it into a hydrophilic moiety and electrostatically dissociates the carrier and virus. Efficacious and specific delivery was proven by transduction of a photosensitive protein (KillerRed), enabling significant limitation in tumor growth in vivo with photodynamic therapy. An approximate 2.44-fold reduction in tumor weight was achieved after a 2-week course, compared with control groups. Furthermore, conjugation of the AAV2 with iron oxide nanoparticles ("magnetized" AAV2) facilitated magnetic resonance imaging tracking of the virus in vivo. Taken together, the solid tumor microenvironment promotes bioreduction of the lactate-responsive carrier, providing rapid and specific delivery of AAV2 for light-triggered virotherapy via systemic administration.
Hard‐setting soils
Publisher: Wiley
Date: 06-1987
A Comparison of Washing Methods for Hair Mineral Analysis: Internal Versus External Effects
Publisher: Springer Science and Business Media LLC
Date: 27-05-2012
DOI: 10.1007/S12011-012-9456-Z
Abstract: A major difficulty in hair elemental (mineral) analysis for biomonitoring is adequate understanding of the effectiveness of washing procedures. A review of washing protocols used in hair analysis publications showed little consensus with regard to solvents and surfactants used, washing times, and number of washing stages. Two washing approaches were subsequently used to compare their influence on internal and external surface elemental signals determined with time-of-flight secondary ion mass spectrometry. Na, K, Ca, Mg, and Fe were assessed with regard to their relative signal compared to carbon. Both washing methods had similar effect. All elements except for Fe appear to be removed from the surface of the hair as well as from inside the hair. Only the internal Fe content changed with washing and could indicate that external surface bound Fe may not be removed with most washing procedures. It is shown that washing procedures can have a significant effect on reducing the internal elemental signal levels in hair.
QCM-D and ToF-SIMS Investigation to Deconvolute the Relationship between Lipid Adsorption and Orientation on Lipase Activity
Publisher: American Chemical Society (ACS)
Date: 11-09-2015
DOI: 10.1021/ACS.LANGMUIR.5B02476
Abstract: Quartz crystal microbalance with dissipation (QCM-D) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) were used to provide insights into the relationship between lipid adsorption kinetics and molecular behavior in porous silica particles of varying hydrophobicities on lipase activity. Lipase (an interfacial enzyme that cleaves ester bonds to break down lipids to fatty acids and monoglycerides) activity was controlled by loading triglycerides at different surface coverages in hydrophilic and hydrophobic porous silica particles. The rate of lipid adsorption increased 2-fold for the hydrophobic surface compared to the hydrophilic surface. However, for submonolayer lipid coverage, the hydrophilic surface enhanced lipase activity 4-fold, whereas the hydrophobic surface inhibited lipase activity 16-fold, compared to lipid droplets in water. A difference in lipid orientation for low surface coverage, evidenced by ToF-SIMS, indicated that lipid adsorbs to hydrophilic silica in a conformation promoting hydrolysis. Multilayer coverage on hydrophobic and hydrophilic surfaces was indistinguishable with ToF-SIMS analysis. Increased lipid adsorption for both substrates facilitated digestion kinetics comparable to a conventional emulsion. Improved understanding of the interfacial adsorption and orientation of lipid and its digestibility in porous silica has implications in improving the uptake of pharmaceuticals and nutrients from lipid-based delivery systems.
Chemical Mechanisms of Nanoparticle Radiosensitization and Radioprotection: A Review of Structure-Function Relationships Influencing Reactive Oxygen Species
Publisher: MDPI AG
Date: 16-01-2020
DOI: 10.3390/IJMS21020579
Abstract: Metal nanoparticles are of increasing interest with respect to radiosensitization. The physical mechanisms of dose enhancement from X-rays interacting with nanoparticles has been well described theoretically, however have been insufficient in adequately explaining radiobiological response. Further confounding experimental observations is ex les of radioprotection. Consequently, other mechanisms have gained increasing attention, especially via enhanced production of reactive oxygen species (ROS) leading to chemical-based mechanisms. Despite the large number of variables differing between published studies, a consensus identifies ROS-related mechanisms as being of significant importance. Understanding the structure-function relationship in enhancing ROS generation will guide optimization of metal nanoparticle radiosensitisers with respect to maximizing oxidative damage to cancer cells. This review highlights the physico-chemical mechanisms involved in enhancing ROS, commonly used assays and experimental considerations, variables involved in enhancing ROS generation and damage to cells and identifies current gaps in the literature that deserve attention. ROS generation and the radiobiological effects are shown to be highly complex with respect to nanoparticle physico-chemical properties and their fate within cells. There are a number of potential biological targets impacted by enhancing, or scavenging, ROS which add significant complexity to directly linking specific nanoparticle properties to a macroscale radiobiological result.
Metallic nanoparticle radiosensitisation of ion radiotherapy: A review
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.EJMP.2018.03.004
Abstract: The use of gold nanoparticle (GNP) and other metal nanoparticle (MNP) radiosensitisers to enhance radiotherapy offers the potential of improved treatment outcomes. Originally intended for use with X-ray therapy, the possibility of enhanced hadron therapy is desirable due to the superior sparing of healthy tissue in hadron therapy compared to conventional X-ray therapy. While MNPs were not expected to be effective radiosensitisers for hadron therapy due to the limited Z dependence of interactions, recent experimental measurements have contradicted this expectation. Key experimental measurements and Monte Carlo simulations of MNP radiosensitisation for hadron irradiation are reviewed in the current work. Numerous experimental measurements have found a large radiosensitisation effect due to MNPs for proton and carbon ion irradiation. Experiments have also indicated that the radiosensitisation is due in large part to enhanced reactive oxygen species (ROS) production. Simulations have found a large radial dose and ROS enhancement on the nanoscale around a single MNP. However, the short range of the dose enhancement is insufficient for a large macroscale dose enhancement or enhanced biological effect in a cell model considering dose to the nucleus from GNPs in the cytoplasm (a distribution observed in most experiments).
Magnetically Guided Viral Transduction of Gene-Based Sensitization for Localized Photodynamic Therapy To Overcome Multidrug Resistance in Breast Cancer Cells.
Publisher: American Chemical Society (ACS)
Date: 15-05-2017
DOI: 10.1021/ACS.BIOCONJCHEM.7B00162
Abstract: Chemotherapy represents a conventional treatment for many cancers at different stages and is either solely prescribed or concomitant to surgery, radiotherapy, or both. However, treatment is tempered in instances of acquired drug resistance in response to either chemotherapy or targeted therapy, leading to therapeutic failure. To overcome this challenge, many studies focus on how cancer cells manipulate their genomes and metabolism to prevent drug influx and facilitate the efflux of accumulated chemotherapy drugs. Herein, we demonstrate magnetic adeno-associated virus serotype 2 (ironized AAV2) has an ability to be magnetically guided and transduce the photosensitive KillerRed protein to enable photodynamic therapy irrespective of drug resistance.
Antagonistic effects of cadmium on lead accumulation in pregnant and non-pregnant mice
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.JHAZMAT.2011.11.016
Abstract: People are frequently exposed to combinations of contaminants but there is a paucity of data on the effects of mixed contaminants at low doses. This study investigated the influence of cadmium (Cd) on lead (Pb) accumulation in pregnant and non-pregnant mice following exposure to contaminated soil. Exposure to Pb from contaminated soils increased Pb accumulation in both pregnant and non-pregnant mice compared to unexposed control animals (pregnant and non-pregnant). Lead accumulation in the liver and kidneys of exposure pregnant mice (40 ± 15 mg Pb kg(-1)) was significantly higher (P<0.05) than concentrations detected in control pregnant mice (<1 mg Pb kg(-1)). The presence of Cd in contaminated soil had a major effect on the Pb and Fe accumulation in the kidneys and liver, respectively. This study shows that Pb uptake is mediated by the presence of Cd in the co-contaminated soil and demonstrates that further research is required to investigate the influence of co-contaminants on human exposure at sub-chronic concentrations.
Hair analysis as a biomonitor for toxicology, disease and health status
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C1CS15021A
Abstract: Hair analysis receives a large amount of academic and commercial interest for wide-ranging applications. However, in many instances, especially for elemental or 'mineral' analysis, the degree of success of analytical interpretation has been quite minimal with respect to the extent of such endeavors. In this critical review we address the questions surrounding hair analysis with specific intent of discovering what hair concentrations can actually relate to in a biogenic sense. This is done from a chemistry perspective to explain why and how elements are incorporated into hair and their meaning. This includes an overview of variables attributed to altering hair concentrations, such as age, gender, melanin content, and other less reported factors. Hair elemental concentrations are reviewed with regard to morbidity, with specific ex les of disease related effects summarized. The application of hair analysis for epidemiology and etiology studies is enforced. A section is dedicated specifically to the area of population studies with regards to mercury, which highlights how endogenous and exogenous incorporation relies on species dependant metabolism and metabolic products. Many of the considerations are relevant to other areas of interest in hair analysis, such as for drug and isotopic analysis. Inclusion of a table of elemental concentrations in hair should act as a valuable reference (298 references).
Use of TOF-SIMS to Study Adsorption and Loading Behavior of Methylene Blue and Papain in a Nano-Porous Silicon Layer
Publisher: American Chemical Society (ACS)
Date: 02-2010
DOI: 10.1016/J.JASMS.2009.10.007
Abstract: TOF-SIMS was applied to study the cross-sectional distribution of methylene blue and papain in porous silicon layers. Elemental and molecular information were used to study their distributions in the porous region and the chemistry of their adsorption. Methylene blue (MW = 284 Da) penetrated to the base to the pores. Positive ions (SiCH(3)(+)) suggest methylene blue binds to the substrate via its methyl groups. Negative fragments (SiOSH(3)(-) and SiO(2)SCH(-)) also suggested chemisorption via O bridging of the substrate Si and methylene blue S. The larger Papain molecule (23,406 Da) distributed itself in a similar manner to methylene blue demonstrating larger molecules can be effectively incorporated into such pore structures.
Cu K-edge XANES: polymer, organic, inorganic spectra, and experimental considerations
Publisher: Cambridge University Press (CUP)
Date: 27-07-2017
DOI: 10.1017/S0885715617000756
Abstract: In pursuit of design and characterisation of Cu adsorbing in thin films, we present data from a large variety of Cu-K edge X-ray Absorption Near Edge Spectroscopy (XANES) spectra obtained from organic and inorganic standards. Additionally, we have explored the impact of beam damage inducing redox alterations. Polymer nanoparticles were tested against films to produce higher concentration s les while maintaining high surface area to bulk effects. Spectra from nanoparticles were highly comparable to thin films of ~8 nm thickness, implying comparable contributions by surface effects on copper association. Finally, we observed no impact on Cu XANES spectra from vitrification with dimethyl sulfoxide to produce amorphous frozen, hydrated s les. The spectra should act as a valuable resource in assisting the design of experiments and identification of copper associations.
Calcium distributions in human hair by ToF-SIMS
Publisher: Elsevier BV
Date: 12-2003
DOI: 10.1016/J.BBAGEN.2003.09.003
Abstract: Calcium distributions on internal and external surfaces of longitudinally sectioned hairs were analysed with Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). Externally, calcium deposits were observed at the cuticle scale edges. Internal sections showed that the bulk of calcium exists within or just inside the cuticle layer. The medulla may or may not be enriched and other localised concentrations exist in one of two forms either associated with granular structures or the hair proteins. Calcium appears to show an affinity for proteins with low sulfur content.
Polyethyleneimine for copper absorption II: kinetics, selectivity and efficiency from seawater
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5RA08029K
Abstract: Nano-thin coatings of glutaraldehyde cross-linked polyethyleneimine effectively and selectively accumulated copper from natural seawater.
The current status of FLASH particle therapy: a systematic review
Publisher: Springer Science and Business Media LLC
Date: 09-05-2023
DOI: 10.1007/S13246-023-01266-Z
Abstract: Particle therapies are becoming increasingly available clinically due to their beneficial energy deposition profile, sparing healthy tissues. This may be further promoted with ultra-high dose rates, termed FLASH. This review comprehensively summarises current knowledge based on studies relevant to proton- and carbon-FLASH therapy. As electron-FLASH literature presents important radiobiological findings that form the basis of proton and carbon-based FLASH studies, a summary of key electron-FLASH papers is also included. Preclinical data suggest three key mechanisms by which proton and carbon-FLASH are able to reduce normal tissue toxicities compared to conventional dose rates, with equipotent, or enhanced, tumour kill efficacy. However, a degree of caution is needed in clinically translating these findings as: most studies use transmission and do not conform the Bragg peak to tumour volume mechanistic understanding is still in its infancy stringent verification of dosimetry is rarely provided biological assays are prone to limitations which need greater acknowledgement.
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