Imperial College London

ProfessorAlexandraPorter

Faculty of EngineeringDepartment of Materials

Professor of Bio-imaging and Analysis
 
 
 
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Contact

 

+44 (0)20 7594 9691a.porter

 
 
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Location

 

B341 Royal School of MinesRoyal School of MinesSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

181 results found

Robinson RK, Birrell MA, Wortley MA, Dubuis ED, Chen S, McGilvery CM, Hu S, Bonvini SJ, Maher SA, Adcock JJ, Mudway I, Porter AE, Tetley TD, Belvisi MGet al., 2016, Diesel Activates Airway Sensory Nerves To Initiate Respiratory Symptoms, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Perez JE, Contreras MF, Vilanova E, Felix LP, Margineanu MB, Luongo G, Porter AE, Dunlop IE, Ravasi T, Kosel Jet al., 2015, Cytotoxicity and intracellular dissolution of nickel nanowires., Nanotoxicology, Vol: Accepted

The assessment of cytotoxicity of nanostructures is a fundamental step for their development as biomedical tools. As widely used nanostructures, nickel nanowires (Ni NWs) seem promising candidates for such applications. In this work, Ni NWs were synthesized and then characterized using vibrating sample magnetometry, energy dispersive X-Ray analysis and electron microscopy. After exposure to the NWs, cytotoxicity was evaluated in terms of cell viability, cell membrane damage and induced apoptosis/necrosis on the model human cell line HCT 116. The influence of NW to cell ratio (10:1 to 1000:1) and exposure times up to 72 hours was analyzed for Ni NWs of 5.4 µm in length, as well as for Ni ions. The results show that cytotoxicity markedly increases past 24 hours of incubation. Cellular uptake of NWs takes place through the phagocytosis pathway, with a fraction of the dose of NWs dissolved inside the cells. Cell death results from a combination of apoptosis and necrosis, where the latter is the outcome of the secondary necrosis pathway. The cytotoxicity of Ni ions and Ni NWs dissolution studies suggest a synergistic toxicity between NW aspect ratio and dissolved Ni, with the cytotoxic effects markedly increasing after 24 hours of incubation.

Journal article

Sarkar S, Leo BF, Carranza C, Chen S, Rivas-Santiago C, Porter AE, Ryan MP, Gow A, Chung KF, Tetley TD, Zhang JJ, Georgopoulos PG, Ohman-Strickland PA, Schwander Set al., 2015, Modulation of human macrophage responses to mycobacterium tuberculosis by silver nanoparticles of different size and surface modification, PLOS One, Vol: 10, ISSN: 1932-6203

Exposure to silver nanoparticles (AgNP) used in consumer products carries potential health risks including increased susceptibility to infectious pathogens. Systematic assessments of antimicrobial macrophage immune responses in the context of AgNP exposure are important because uptake of AgNP by macrophages may lead to alterations of innate immune cell functions. In this study we examined the effects of exposure to AgNP with different particle sizes (20 and 110 nm diameters) and surface chemistry (citrate or polyvinlypyrrolidone capping) on cellular toxicity and innate immune responses against Mycobacterium tuberculosis (M.tb) by human monocyte-derived macrophages (MDM). Exposures of MDM to AgNP significantly reduced cellular viability, increased IL8 and decreased IL10 mRNA expression. Exposure of M.tb-infected MDM to AgNP suppressed M.tb-induced expression of IL1B, IL10, and TNFA mRNA. Furthermore, M.tb-induced IL-1β, a cytokine critical for host resistance to M.tb, was inhibited by AgNP but not by carbon black particles indicating that the observed immunosuppressive effects of AgNP are particle specific. Suppressive effects of AgNP on the M.tb-induced host immune responses were in part due to AgNP-mediated interferences with the TLR signaling pathways that culminate in the activation of the transcription factor NF-κB. AgNP exposure suppressed M.tb-induced expression of a subset of NF-κB mediated genes (CSF2, CSF3, IFNG, IL1A, IL1B, IL6, IL10, TNFA, NFKB1A). In addition, AgNP exposure increased the expression of HSPA1A mRNA and the corresponding stress-induced Hsp72 protein. Up-regulation of Hsp72 by AgNP can suppress M.tb-induced NF-κB activation and host immune responses. The observed ability of AgNP to modulate infectious pathogen-induced immune responses has important public health implications.

Journal article

Robinson R, Wortley M, Dubuis E, Chen S, Hu S, Bonvini S, Maher S, Adcock J, Mudway I, Porter A, Tetley T, Birrell M, Belvisi Met al., 2015, Organic components of diesel exhaust particles (DEP) activate airway sensory nerves via transient receptor potential ankrin-1 (TRPA1) ion channels, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Goode AE, Gonzalez Carter DA, Motskin M, Pienaar IS, Chen S, Hu S, Ruenraroengsak P, Ryan M, Shaffer MSP, Dexter DT, Porter AEet al., 2015, High resolution and dynamic imaging of biopersistence and bioreactivity of extra and intracellular MWNTs exposed to microglial cells, Biomaterials, Vol: 70, Pages: 57-70, ISSN: 1878-5905

Multi-walled carbon nanotubes (MWNTs) are increasingly being developed both as neuro-therapeutic drug delivery systems to the brain and as neural scaffolds to drive tissue regeneration across lesion sites. MWNTs with different degrees of acid oxidation may have different bioreactivities and propensities to aggregate in the extracellular environment, and both individualised and aggregated MWNTs may be expected to be found in the brain. Before practical application, it is vital to understand how both aggregates and individual MWNTs will interact with local phagocytic immune cells, the microglia, and ultimately to determine their biopersistence in the brain. The processing of extra- and intracellular MWNTs (both pristine and when acid oxidised) by microglia was characterised across multiple length scales by correlating a range of dynamic, quantitative and multi-scale techniques, including: UV-vis spectroscopy, light microscopy, focussed ion beam scanning electron microscopy and transmission electron microscopy. Dynamic, live cell imaging revealed the ability of microglia to break apart and internalise micron-sized extracellular agglomerates of acid oxidised MWNT, but not pristine MWNTs. The total amount of MWNTs internalised by, or strongly bound to, microglia was quantified as a function of time. Neither the significant uptake of oxidised MWNTs, nor the incomplete uptake of pristine MWNTs affected microglial viability, pro-inflammatory cytokine release or nitric oxide production. However, after 24 hrs exposure to pristine MWNTs, a significant increase in the production of reactive oxygen species was observed. Small aggregates and individualised oxidised MWNTs were present in the cytoplasm and vesicles, including within multilaminar bodies, after 72 hours. Some evidence of morphological damage to oxidised MWNT structure was observed including highly disordered graphitic structures, suggesting possible biodegradation. This work demonstrates the utility of dynamic, quant

Journal article

Mukherjee D, Porter A, Ryan M, Schwander S, Chung KF, Tetley T, Zhang J, Georgopoulos Pet al., 2015, Modeling in vivo interactions of engineered nanoparticles in the pulmonary alveolar lining fluid, Nanomaterials, Vol: 5, Pages: 1223-1249, ISSN: 2079-4991

Increasing use of engineered nanomaterials (ENMs) in consumer products may result in widespread human inhalation exposures. Due to their high surface area per unit mass, inhaled ENMs interact with multiple components of the pulmonary system, and these interactions affect their ultimate fate in the body. Modeling of ENM transport and clearance in vivo has traditionally treated tissues as well-mixed compartments, without consideration of nanoscale interaction and transformation mechanisms. ENM agglomeration, dissolution and transport, along with adsorption of biomolecules, such as surfactant lipids and proteins, cause irreversible changes to ENM morphology and surface properties. The model presented in this article quantifies ENM transformation and transport in the alveolar air to liquid interface and estimates eventual alveolar cell dosimetry. This formulation brings together established concepts from colloidal and surface science, physics, and biochemistry to provide a stochastic framework capable of capturing essential in vivo processes in the pulmonary alveolar lining layer. The model has been implemented for in vitro solutions with parameters estimated from relevant published in vitro measurements and has been extended here to in vivo systems simulating human inhalation exposures. Applications are presented for four different ENMs, and relevant kinetic rates are estimated, demonstrating an approach for improving human in vivo pulmonary dosimetry.

Journal article

Munusamy P, Wang C, Engelhard MH, Baer DR, Smith JN, Liu C, Kodali V, Thrall BD, Chen S, Porter AE, Ryan MPet al., 2015, Comparison of 20nm silver nanoparticles synthesized with and without a gold core: Structure, dissolution in cell culture media, and biological impact on macrophages, Biointerphases, Vol: 10, ISSN: 1934-8630

Widespread use of silver nanoparticles raises questions of environmental and biological impact. Many synthesis approaches are used to produce pure silver and silver-shell gold-core particles optimized for specific applications. Since both nanoparticles and silver dissolved from the particles may impact the biological response, it is important to understand the physicochemical characteristics along with the biological impact of nanoparticles produced by different processes. The authors have examined the structure, dissolution, and impact of particle exposure to macrophage cells of two 20 nm silver particles synthesized in different ways, which have different internal structures. The structures were examined by electron microscopy and dissolution measured in Rosewell Park Memorial Institute media with 10% fetal bovine serum. Cytotoxicity and oxidative stress were used to measure biological impact on RAW 264.7 macrophage cells. The particles were polycrystalline, but 20 nm particles grown on gold seed particles had smaller crystallite size with many high-energy grain boundaries and defects, and an apparent higher solubility than 20 nm pure silver particles. Greater oxidative stress and cytotoxicity were observed for 20 nm particles containing the Au core than for 20 nm pure silver particles. A simple dissolution model described the time variation of particle size and dissolved silver for particle loadings larger than 9 μg/ml for the 24-h period characteristic of many in-vitro studies.

Journal article

Theodorou IG, Botelho D, Schwander S, Zhang J, Chung KF, Tetley TD, Shaffer MSP, Gow A, Ryan MP, Porter AEet al., 2015, Static and Dynamic Microscopy of the Chemical Stability and Aggregation State of Silver Nanowires in Components of <i>Murine</i> Pulmonary Surfactant, ENVIRONMENTAL SCIENCE & TECHNOLOGY, Vol: 49, Pages: 8048-8056, ISSN: 0013-936X

Journal article

Theodorou I, Porter AE, Ryan M, leo BF, López-Heras Met al., 2015, Towards understanding the antibacterial activity of Ag nanoparticles: electron microscopy in the analysis of the materials-biology interface in the lung, Environmental Science: Nano, Vol: 2, Pages: 312-326, ISSN: 2051-8161

Bacterial infections of the pulmonary system are increasing. With almost half of today's infections beingcaused by strains of bacteria that are resistant to existing conventional antibiotics, there is an urgent needfor the development of novel therapeutic platforms. Silver nanoparticles (AgNPs) have been receivingincreasing attention due to their unique antibacterial properties, and whilst the biological efficacy of silveris well known, the mechanisms by which AgNPs degrade within cells and how these processes correlate totheir bioreactivity are poorly understood. This review summarises the current knowledge on thebactericidal pathways of AgNPs and discusses the challenges to be faced before we are able to developefficient and safe antibacterial agents for the treatment of bacterial infections in the lung.

Journal article

Sweeney S, Theodorou IG, Zambianchi M, Chen S, Gow A, Schwander S, Zhang JJ, Chung KF, Shaffer MS, Ryan MP, Porter AE, Tetley TDet al., 2015, Silver nanowire interactions with primary human alveolar type-II epithelial cell secretions: contrasting bioreactivity with human alveolar type-I and type-II epithelial cells., Nanoscale, Vol: 7, Pages: 10398-10409, ISSN: 2040-3372

Inhaled nanoparticles have a high deposition rate in the alveolar units of the deep lung. The alveolar epithelium is composed of type-I and type-II epithelial cells (ATI and ATII respectively) and is bathed in pulmonary surfactant. The effect of native human ATII cell secretions on nanoparticle toxicity is not known. We investigated the cellular uptake and toxicity of silver nanowires (AgNWs; 70 nm diameter, 1.5 μm length) with human ATI-like cells (TT1), in the absence or presence of Curosurf® (a natural porcine pulmonary surfactant with a low amount of protein) or harvested primary human ATII cell secretions (HAS; containing both the complete lipid as well as the full protein complement of human pulmonary surfactant i.e. SP-A, SP-B, SP-C and SP-D). We hypothesised that Curosurf® or HAS would confer improved protection for TT1 cells, limiting the toxicity of AgNWs. In agreement with our hypothesis, HAS reduced the inflammatory and reactive oxygen species (ROS)-generating potential of AgNWs with exposed TT1 cells. For example, IL-8 release and ROS generation was reduced by 38% and 29%, respectively, resulting in similar levels to that of the non-treated controls. However in contrast to our hypothesis, Curosurf® had no effect. We found a significant reduction in AgNW uptake by TT1 cells in the presence of HAS but not Curosurf. Furthermore, we show that the SP-A and SP-D are likely to be involved in this process as they were found to be specifically bound to the AgNWs. While ATI cells appear to be protected by HAS, evidence suggested that ATII cells, despite no uptake, were vulnerable to AgNW exposure (indicated by increased IL-8 release and ROS generation and decreased intracellular SP-A levels one day post-exposure). This study provides unique findings that may be important for the study of lung epithelial-endothelial translocation of nanoparticles in general and associated toxicity within the alveolar unit.

Journal article

Melbourne J, Clancy A, Seiffert J, Skepper J, Tetley TD, Shaffer MS, Porter Aet al., 2015, An investigation of the carbon nanotube - Lipid interface and its impact upon pulmonary surfactant lipid function., Biomaterials, Vol: 55, Pages: 24-32, ISSN: 1878-5905

Multiwalled carbon nanotubes (MWCNTs) are now synthesized on a large scale, increasing the risk of occupational inhalation. However, little is known of the MWCNT-pulmonary surfactant (PS) interface and its effect on PS functionality. The Langmuir-Blodgett trough was used to evaluate the impact of MWCNTs on fundamental properties of PS lipids which influence PS function, i.e. compression resistance and maximum obtainable pressure. Changes were found to be MWCNT length-dependent. 'Short' MWCNTs (1.1 μm, SD = 0.61) penetrated the lipid film, reducing the maximum interfacial film pressure by 10 mN/m (14%) in dipalmitoylphosphatidylcholine (DPPC) and PS, at an interfacial MWCNT-PS lipid mass ratio range of 50:1 to 1:1. 'Long' commercial MWCNTs (2.1 μm, SD = 1.2) caused compression resistance at the same mass loadings. 'Very long' MWCNTs (35 μm, SD = 19) sequestered DPPC and were squeezed out of the DPPC film. High resolution transmission electron microscopy revealed that all MWCNT morphologies formed DPPC coronas with ordered arrangements. These results provide insight into how nanoparticle aspect ratio affects the interaction mechanisms with PS, in its near-native state at the air-water interface.

Journal article

Klosowski MM, Friederichs RJ, Nichol R, Antolin N, Carzaniga R, Windl W, Best SM, Shefelbine SJ, McComb DW, Porter AEet al., 2015, Probing carbonate in bone forming minerals on the nanometre scale, Acta Biomaterialia, Vol: 20, Pages: 129-139, ISSN: 1878-7568

To devise new strategies to treat bone disease in an ageing society, a more detailed characterisation of the process by which bone mineralises is needed. In vitro studies have suggested that carbonated mineral might be a precursor for deposition of bone apatite. Increased carbonate content in bone may also have significant implications in altering the mechanical properties, for example in diseased bone. However, information about the chemistry and coordination environment of bone mineral, and their spatial distribution within healthy and diseased tissues, is lacking. Spatially resolved analytical transmission electron microscopy is the only method available to probe this information at the length scale of the collagen fibrils in bone. In this study, scanning transmission electron microscopy combined with electron energy-loss spectroscopy (STEM-EELS) was used to differentiate between calcium-containing biominerals (hydroxyapatite, carbonated hydroxyapatite, beta-tricalcium phosphate and calcite). A carbon K-edge peak at 290 eV is a direct marker of the presence of carbonate. We found that the oxygen K-edge structure changed most significantly between minerals allowing discrimination between calcium phosphates and calcium carbonates. The presence of carbonate in carbonated HA (CHA) was confirmed by the formation of peak at 533 eV in the oxygen K-edge. These observations were confirmed by simulations using density functional theory. Finally, we show that this method can be utilised to map carbonate from the crystallites in bone. We propose that our calibration library of EELS spectra could be extended to provide spatially resolved information about the coordination environment within bioceramic implants to stimulate the development of structural biomaterials.

Journal article

Seiffert J, Hussain F, Wiegman C, Li F, Bey L, Baker W, Porter A, Ryan MP, Chang Y, Gow A, Zhang J, Zhu J, Tetley TD, Chung KFet al., 2015, Pulmonary Toxicity of Instilled Silver Nanoparticles: Influence of Size, Coating and Rat Strain, PLOS ONE, Vol: 10, ISSN: 1932-6203

Journal article

Hembury M, Chiappini C, Bertazzo S, Kalber TL, Drisko GL, Ogunlade O, Walker-Samuel S, Krishna KS, Jumeaux C, Beard P, Kumar CSSR, Porter AE, Lythgoe MF, Boissiere C, Sanchez C, Stevens MMet al., 2015, Gold-silica quantum rattles for multimodal imaging and therapy, Proceedings of the National Academy of Sciences, Vol: 112, Pages: 1959-1964, ISSN: 1091-6490

Gold quantum dots exhibit distinctive optical and magnetic behaviors compared with larger gold nanoparticles. However, their unfavorable interaction with living systems and lack of stability in aqueous solvents has so far prevented their adoption in biology and medicine. Here, a simple synthetic pathway integrates gold quantum dots within a mesoporous silica shell, alongside larger gold nanoparticles within the shell’s central cavity. This “quantum rattle” structure is stable in aqueous solutions, does not elicit cell toxicity, preserves the attractive near-infrared photonics and paramagnetism of gold quantum dots, and enhances the drug-carrier performance of the silica shell. In vivo, the quantum rattles reduced tumor burden in a single course of photothermal therapy while coupling three complementary imaging modalities: near-infrared fluorescence, photoacoustic, and magnetic resonance imaging. The incorporation of gold within the quantum rattles significantly enhanced the drug-carrier performance of the silica shell. This innovative material design based on the mutually beneficial interaction of gold and silica introduces the use of gold quantum dots for imaging and therapeutic applications.

Journal article

Marchetti M, Shaffer MSP, Zambianchi M, Chen S, Superti F, Schwander S, Gow A, Zhang JJ, Chung KF, Ryan MP, Porter AE, Tetley TDet al., 2015, Adsorption of surfactant protein D from human respiratory secretions by carbon nanotubes and polystyrene nanoparticles depends on nanomaterial surface modification and size, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 370, ISSN: 0962-8436

Journal article

Chen S, Goode AE, Skepper JN, Thorley AJ, Seiffert JM, Chung KF, Tetley TD, Shaffer MSP, Ryan MP, Porter AEet al., 2015, Avoiding artefacts during electron microscopy of silver nanomaterials exposed to biological environments, Journal of Microscopy, Vol: 261, Pages: 157-166, ISSN: 1365-2818

Electron microscopy has been applied widely to study the interaction of nanomaterials with proteins, cells and tissues at nanometre scale. Biological material is most commonly embedded in thermoset resins to make it compatible with the high vacuum in the electron microscope. Room temperature sample preparation protocols developed over decades provide contrast by staining cell organelles, and aim to preserve the native cell structure. However, the effect of these complex protocols on the nanomaterials in the system is seldom considered. Any artefacts generated during sample preparation may ultimately interfere with the accurate prediction of the stability and reactivity of the nanomaterials. As a case study, we review steps in the room temperature preparation of cells exposed to silver nanomaterials (AgNMs) for transmission electron microscopy imaging and analysis. In particular, embedding and staining protocols, which can alter the physicochemical properties of AgNMs and introduce artefacts thereby leading to a misinterpretation of silver bioreactivity, are scrutinized. Recommendations are given for the application of cryogenic sample preparation protocols, which simultaneously fix both particles and diffusible ions. By being aware of the advantages and limitations of different sample preparation methods, compromises or selection of different correlative techniques can be made to draw more accurate conclusions about the data. Lay description: With increasing commercialization of silver nanomaterials (AgNMs) comes a concomitant need to understand occupational health, public safety and environmental implications of these materials. Nanoscale studies of the complex bio-nano interface lie at the heart of technical challenges. Despite numerous reports, there is no consensus regarding biological mechanisms enacted by AgNMs. Powerful new electron microscopy techniques can be used to visualize the interaction of the AgNMs with tissues. However, it is extremely difficult to

Journal article

Theodorou IG, Ryan MP, Tetley TD, Porter AEet al., 2014, Inhalation of silver nanomaterials - seeing the risks, International Journal of Molecular Sciences, Vol: 15, Pages: 23936-23974, ISSN: 1661-6596

Demand for silver engineered nanomaterials (ENMs) is increasing rapidly in optoelectronic and in health and medical applications due to their antibacterial, thermal, electrical conductive, and other properties. The continued commercial up-scaling of ENM production and application needs to be accompanied by an understanding of the occupational health, public safety and environmental implications of these materials. There have been numerous in vitro studies and some in vivo studies of ENM toxicity but their results are frequently inconclusive. Some of the variability between studies has arisen due to a lack of consistency between experimental models, since small differences between test materials can markedly alter their behaviour. In addition, the propensity for the physicochemistry of silver ENMs to alter, sometimes quite radically, depending on the environment they encounter, can profoundly alter their bioreactivity. Consequently, it is important to accurately characterise the materials before use, at the point of exposure and at the nanomaterial-tissue, or “nanobio”, interface, to be able to appreciate their environmental impact. This paper reviews current literature on the pulmonary effects of silver nanomaterials. We focus our review on describing whether, and by which mechanisms, the chemistry and structure of these materials can be linked to their bioreactivity in the respiratory system. In particular, the mechanisms by which the physicochemical properties (e.g., aggregation state, morphology and chemistry) of silver nanomaterials change in various biological milieu (i.e., relevant proteins, lipids and other molecules, and biofluids, such as lung surfactant) and affect subsequent interactions with and within cells will be discussed, in the context not only of what is measured but also of what can be visualized.

Journal article

Goode AE, Porter AE, Ryan MP, McComb DWet al., 2014, Correlative electron and X-ray microscopy: probing chemistry and bonding with high spatial resolution, Nanoscale, Vol: 7, Pages: 1534-1548, ISSN: 2040-3372

Two powerful and complementary techniques for chemical characterisation of nanoscale systems are electron energy-loss spectroscopy in the scanning transmission electron microscope, and X-ray absorption spectroscopy in the scanning transmission X-ray microscope. A correlative approach to spectro-microscopy may not only bridge the gaps in spatial and spectral resolution which exist between the two instruments, but also offer unique opportunities for nanoscale characterisation. This review will discuss the similarities of the two spectroscopy techniques and the state of the art for each microscope. Case studies have been selected to illustrate the benefits and limitations of correlative electron and X-ray microscopy techniques. In situ techniques and radiation damage are also discussed.

Journal article

Hu S, Chen S, Menzel R, Goode AD, Ryan MP, Porter AE, Shaffer MSPet al., 2014, Aqueous dispersions of oligomer-grafted carbon nanomaterials with controlled surface charge and minimal framework damage, FARADAY DISCUSSIONS, Vol: 173, Pages: 273-285, ISSN: 1359-6640

Journal article

Mukherjee D, Royce SG, Sarkar S, Thorley A, Schwander S, Ryan MP, Porter AE, Chung KF, Tetley TD, Zhang J, Georgopoulos PGet al., 2014, Modeling in vitro cellular responses to silver nanoparticles, Journal of Toxicology, Vol: 2014, ISSN: 1687-8205

Engineered nanoparticles (NPs) have been widely demonstrated to induce toxic effects to various cell types. In vitro cell exposure systems have high potential for reliable, high throughput screening of nanoparticle toxicity, allowing focusing on particular pathways while excluding unwanted effects due to other cells or tissue dosimetry. The work presented here involves a detailed biologically based computational model of cellular interactions with NPs; it utilizes measurements performed in human cell culture systems in vitro, to develop a mechanistic mathematical model that can support analysis and prediction of in vivo effects of NPs. The model considers basic cellular mechanisms including proliferation, apoptosis, and production of cytokines in response to NPs. This new model is implemented for macrophages and parameterized using in vitro measurements of changes in cellular viability and mRNA levels of cytokines: TNF, IL-1b, IL-6, IL-8, and IL-10. The model includes in vitro cellular dosimetry due to nanoparticle transport and transformation. Furthermore, the model developed here optimizes the essential cellular parameters based on in vitro measurements, and provides a "stepping stone" for the development of more advanced in vivo models that will incorporate additional cellular and NP interactions.

Journal article

Mukherjee D, Leo BF, Royce SG, Porter AE, Ryan MP, Schwander S, Chung KF, Tetley TD, Zhang J, Georgopoulos PGet al., 2014, Modeling physicochemical interactions affecting in vitro cellular dosimetry of engineered nanomaterials: application to nanosilver, JOURNAL OF NANOPARTICLE RESEARCH, Vol: 16, ISSN: 1388-0764

Journal article

Baer DR, Munusamy P, Smith JN, Karakoti AS, Kuchibhatla SVNT, Liu C, Wang C, Chen S, Porter AE, Ryan MPet al., 2014, Time dependent transformations of ceria and silver nanoparticles during synthesis, storage, and in biological media, 248th National Meeting of the American-Chemical-Society (ACS), Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727

Conference paper

Harris-Birtill D, Singh M, Zhou Y, Gallina ME, Cass T, Elson DSet al., 2014, Gold Nanorod Reshaping using a Continuous Wave Laser, CLEO: Applications and Technology, Publisher: Optical Society of America

Conference paper

Chen S, Hu S, Smith EF, Ruenraroengsak P, Thorley AJ, Menzel R, Goode AE, Ryan MP, Tetley TD, Porter AE, Shaffer MSPet al., 2014, Aqueous cationic, anionic and non-ionic multi-walled carbon nanotubes, functionalised with minimal framework damage, for biomedical application, Biomaterials, Vol: 35, Pages: 4729-4738

Journal article

Sarkar S, Zhang L, Subramaniam P, Lee K-B, Garfunkel E, Strickland PAO, Mainelis G, Lioy PJ, Tetley TD, Chung KF, Zhang J, Ryan M, Porter A, Schwander Set al., 2014, Variability in Bioreactivity Linked to Changes in Size and Zeta Potential of Diesel Exhaust Particles in Human Immune Cells, PLOS One, Vol: 9, ISSN: 1932-6203

Acting as fuel combustion catalysts to increase fuel economy, cerium dioxide (ceria, CeO2) nanoparticles have been used inEurope as diesel fuel additives (EnviroxTM). We attempted to examine the effects of particles emitted from a diesel engineburning either diesel (diesel exhaust particles, DEP) or diesel doped with various concentrations of CeO2 (DEP-Env) on innateimmune responses in THP-1 and primary human peripheral blood mononuclear cells (PBMC). Batches of DEP and DEP-Envwere obtained on three separate occasions using identical collection and extraction protocols with the aim of determiningthe reproducibility of particles generated at different times. However, we observed significant differences in size and surfacecharge (zeta potential) of the DEP and DEP-Env across the three batches. We also observed that exposure of THP-1 cells andPBMC to identical concentrations of DEP and DEP-Env from the three batches resulted in statistically significant differencesin bioreactivity as determined by IL-1b, TNF-a, IL-6, IFN-c, and IL-12p40 mRNA (by qRT-PCR) and protein expression (byELISPOT assays). Importantly, bioreactivity was noted in very tight ranges of DEP size (60 to 120 nm) and zeta potential (237to 241 mV). Thus, these physical properties of DEP and DEP-Env were found to be the primary determinants of thebioreactivity measured in this study. Our findings also point to the potential risk of over- or under- estimation of expectedbioreactivity effects (and by inference of public health risks) from bulk DEP use without taking into account potential batchto-batchvariations in physical (and possibly chemical) properties.

Journal article

Goode AE, Hine NDM, Chen S, Bergin SD, Shaffer MSP, Ryan MP, Haynes PD, Porter AE, McComb DWet al., 2014, Mapping functional groups on oxidised multi-walled carbon nanotubes at the nanometre scale, Chemical Communications, ISSN: 1364-548X

Journal article

Schwander S, Zhang JJ, Tetley T, Gow A, Chung KF, Ryan M, Porter A, Sarkar Set al., 2014, Silver nanoparticles impair human antimicrobial immune responses, JOURNAL OF IMMUNOLOGY, Vol: 192, ISSN: 0022-1767

Journal article

Klosowski M, Porter AE, Shefelbine SJ, McComb DWet al., 2014, Analytical electron microscopy of bone and mineralized tissue, Handbook of Imaging in Biological Mechanics, Pages: 491-505, ISBN: 9781466588134

In this chapter, the use of transmission electron microscopy (TEM) techniques for investigation of mineralized tissues is reviewed. The high-resolution imaging capabilities of modern TEM instruments are yielding new insights into the nanostructure of materials such as bone and dentine that improve our understanding of the complex multiscale structures. Analytical techniques such as electron energy-loss spectroscopy and energy dispersive x-ray analysis in the TEM are providing insights into chemistry and bonding in mineralized tissues with molecular-scale spatial resolution. Dual beam focused ion beam instruments have revolutionized sample preparation; TEM samples can be prepared from site-specific regions of interest such as cracks and interfaces. In combination, these methods can shed light on the exact relationship between the mineral and organic phases in mineralized tissues and ultimately provide unique insights in the complex relationship between chemistry, structure, and bonding with bone-related pathologies.

Book chapter

Tsigkou O, Labbaf S, Stevens MM, Porter AE, Jones JRet al., 2014, Monodispersed Bioactive Glass Submicron Particles and Their Effect on Bone Marrow and Adipose Tissue-Derived Stem Cells, ADVANCED HEALTHCARE MATERIALS, Vol: 3, Pages: 115-125, ISSN: 2192-2640

Journal article

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