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Dawson, Kenneth A.
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Dawson, Kenneth A.
Official Name
Dawson, Kenneth A.
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Now showing 1 - 10 of 34
- PublicationIn depth characterisation of the biomolecular coronas of polymer coated inorganic nanoparticles with differential centrifugal sedimentation(Springer, 2021-03-19)
; ; ; ; ; ; ; Advances in nanofabrication methods have enabled the tailoring of new strategies towards the controlled production of nanoparticles with attractive applications in healthcare. In many cases, their characterisation remains a big challenge, particularly for small-sized functional nanoparticles of 5 nm diameter or smaller, where current particle sizing techniques struggle to provide the required sensitivity and accuracy. There is a clear need for the development of new reliable characterisation approaches for the physico-chemical characterisation of nanoparticles with significant accuracy, particularly for the analysis of the particles in the presence of complex biological fluids. Herein, we show that the Differential Centrifugal Sedimentation can be utilised as a high-precision tool for the reliable characterisation of functional nanoparticles of different materials. We report a method to correlate the sedimentation shift with the polymer and biomolecule adsorption on the nanoparticle surface, validating the developed core-shell model. We also highlight its limit when measuring nanoparticles of smaller size and the need to use several complementary methods when characterising nanoparticle corona complexes.241Scopus© Citations 13 - PublicationMapping protein binding sites on the biomolecular corona of nanoparticles(Springer Nature, 2015-03-30)
; ; ; ; ; ; ; Nanoparticles in a biological milieu are known to form a sufficiently long-lived and well-organized 'corona' of biomolecules to confer a biological identity to the particle. Because this nanoparticle-biomolecule complex interacts with cells and biological barriers, potentially engaging with different biological pathways, it is important to clarify the presentation of functional biomolecular motifs at its interface. Here, we demonstrate that by using antibody-labelled gold nanoparticles, differential centrifugal sedimentation and various imaging techniques it is possible to identify the spatial location of proteins, their functional motifs and their binding sites. We show that for transferrin-coated polystyrene nanoparticles only a minority of adsorbed proteins exhibit functional motifs and the spatial organization appears random, which is consistent, overall, with a stochastic and irreversible adsorption process. Our methods are applicable to a wide array of nanoparticles and can offer a microscopic molecular description of the biological identity of nanoparticles.531Scopus© Citations 298 - PublicationNanoparticle accumulation and transcytosis in brain endothelial cell layers(Royal Society of Chemistry, 2013-09)
; ; ; ; ; ; The blood–brain barrier (BBB) is a selective barrier, which controls and limits access to the central nervous system (CNS). The selectivity of the BBB relies on specialized characteristics of the endothelial cells that line the microvasculature, including the expression of intercellular tight junctions, which limit paracellular permeability. Several reports suggest that nanoparticles have a unique capacity to cross the BBB. However, direct evidence of nanoparticle transcytosis is difficult to obtain, and we found that typical transport studies present several limitations when applied to nanoparticles. In order to investigate the capacity of nanoparticles to access and transport across the BBB, several different nanomaterials, including silica, titania and albumin- or transferrin-conjugated gold nanoparticles of different sizes, were exposed to a human in vitro BBB model of endothelial hCMEC/D3 cells. Extensive transmission electron microscopy imaging was applied in order to describe nanoparticle endocytosis and typical intracellular localisation, as well as to look for evidence of eventual transcytosis. Our results show that all of the nanoparticles were internalised, to different extents, by the BBB model and accumulated along the endo–lysosomal pathway. Rare events suggestive of nanoparticle transcytosis were also observed for several of the tested materials.939Scopus© Citations 104 - PublicationTowards a classification strategy for complex nanostructures(The Royal Society of Chemistry, 2017-03-13)
; ; ; ; ; ; ; ; ; The range of possible nanostructures is so large and continuously growing, that collating and unifying the knowledge connected to them, including their biological activity, is a major challenge. Here we discuss a concept that is based on the connection of microscopic features of the nanomaterials to their biological impacts. We also consider what would be necessary to identify the features that control their biological interactions, and make them resemble each other in a biological context.305Scopus© Citations 41 - PublicationUltrathin Silicon Membranes for in Situ Optical Analysis of Nanoparticle Translocation across a Human Blood-Brain Barrier Model(ACS, 2020-01-28)
; ; ; ; ; ; Here we present a blood-brain barrier (BBB) model that enables high-resolution imaging of nanoparticle (NP) interactions with endothelial cells and the capture of rare NP translocation events. The enabling technology is an ultrathin silicon nitride (SiN) membrane (0.5 μm pore size, 20% porosity, 400 nm thickness) integrated into a dual-chamber platform that facilitates imaging at low working distances (∼50 μm). The platform, the μSiM-BBB (microfluidic silicon membrane-BBB), features human brain endothelial cells and primary astrocytes grown on opposite sides of the membrane. The human brain endothelial cells form tight junctions on the ultrathin membranes and exhibit a significantly higher resistance to FITC-dextran diffusion than commercial membranes. The enhanced optical properties of the SiN membrane allow high-resolution live-cell imaging of three types of NPs, namely, 40 nm PS-COOH, 100 nm PS-COOH, and apolipoprotein E-conjugated 100 nm SiO2, interacting with the BBB. Despite the excellent barrier properties of the endothelial layer, we are able to document rare NP translocation events of NPs localized to lysosomal compartments of astrocytes on the "brain side" of the device. Although the translocation is always low, our data suggest that size and targeting ligand are important parameters for NP translocation across the BBB. As a platform that enables the detection of rare transmission across tight BBB layers, the μSiM-BBB is an important tool for the design of nanoparticle-based delivery of drugs to the central nervous system.817Scopus© Citations 35 - PublicationTime and Space Resolved Uptake Study of Silica Nanoparticles by Human Cells(Royal Society of Chemistry, 2011)
; ; ; ; ; A spatio-temporal mapping of the uptake of silica (SiO2) nanoparticles of different sizes by lung epithelial cells has been obtained. Based on high control of nanoparticle dispersion in cell media and cell exposure, one obtains reproducible and quantitative time-resolved data using a combination of flow cytometry, fluorescence and electron microscopies. We are thereby able to give a rather detailed account of the journey of SiO2 nanoparticles from the early events of uptake to their final sub-cellular localization.1482Scopus© Citations 205 - Publication
221Scopus© Citations 22 - PublicationUsing single nanoparticle tracking obtained by nanophotonic force microscopy to simultaneously characterize nanoparticle size distribution and nanoparticle-surface interactions(Royal Society of Chemistry, 2017-03-13)
; ; ; ; ; Comprehensive characterization of nanomaterials for medical applications is a challenging and complex task due to the multitude of parameters which need to be taken into consideration in a broad range of conditions. Routine methods such as dynamic light scattering or nanoparticle tracking analysis provide some insight into the physicochemical properties of particle dispersions. For nanomedicine applications the information they supply can be of limited use. For this reason, there is a need for new methodologies and instruments that can provide additional data on nanoparticle properties such as their interactions with surfaces. Nanophotonic force microscopy has been shown as a viable method for measuring the force between surfaces and individual particles in the nano-size range. Here we outline a further application of this technique to measure the size of single particles and based on these measurement build the distribution of a sample. We demonstrate its efficacy by comparing the size distribution obtained with nanophotonic force microscopy to established instruments, such as dynamic light scattering and differential centrifugal sedimentation. Our results were in good agreement to those observed with all other instruments. Furthermore, we demonstrate that the methodology developed in this work can be used to study complex particle mixtures and the surface alteration of materials. For all cases studied, we were able to obtain both the size and the interaction potential of the particles with a surface in a single measurement.346Scopus© Citations 8 - PublicationBiomolecular coronas provide the biological identity of nanosized materials(Nature Publishing Group, 2012-12-05)
; ; ; The search for understanding the interactions of nanosized materials with living organisms is leading to the rapid development of key applications, including improved drug delivery by targeting nanoparticles, and resolution of the potential threat of nanotechnological devices to organisms and the environment. Unless they are specifically designed to avoid it, nanoparticles in contact with biological fluids are rapidly covered by a selected group of biomolecules to form a corona that interacts with biological systems. Here we review the basic concept of the nanoparticle corona and its structure and composition, and highlight how the properties of the corona may be linked to its biological impacts. We conclude with a critical assessment of the key problems that need to be resolved in the near future.3421Scopus© Citations 2151 - PublicationTheoretical framework for nanoparticle uptake and accumulation kinetics in dividing cell populationsNano-sized objects interact with biological systems in fundamentally novel ways, thereby holding great promise for targeted drug delivery. It has also been suggested they could constitute a hitherto unseen hazard. Numerous experimental studies in the field are taking place. We consider that the nature of the interactions allows a more fundamental theoretical framework to be developed. In particular, we describe the intimate link that develops between nanoparticle uptake and cell population evolution. Explicit analytical results are given and the theory compared to experimental observations.
523Scopus© Citations 28