Kenneth A Dawson

University College Dublin | UCD

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 sizin...

Polyethylene glycol grafting has played a central role in preparing the surfaces of nano-probes for biological interaction, to extend blood circulation times and to modulate protein recognition and cellular uptake. However, the role of PEG graft dynamics and conformation in determining surface recognition processes is poorly understood primarily du...

X-ray-based analytics are routinely applied in many fields, including physics, chemistry, materials science, and engineering. The full potential of such techniques in the life sciences and medicine, however, has not yet been fully exploited. We highlight current and upcoming advances in this direction. We describe different X-ray-based methodologie...

We describe how magnetic nanoparticles can be used to study intracellular nanoparticle trafficking, and how magnetic extraction may be integrated with downstream analyses to investigate nanoscale decision-making events.

The quality and relevance of nanosafety studies constitute major challenges to ensure their key role as a supporting tool in sustainable innovation, and subsequent competitive economic advantage. However, the number of apparently contradictory and inconclusive research results has increased in the past few years, indicating the need to introduce ha...

Everywhere in our surroundings we increasingly come in contact with nanostructures that have distinctive complex shape features on a scale comparable to the particle itself. Such shape ensembles can be made by modern nano-synthetic methods and many industrial processes. With the ever growing universe of nanoscale shapes, names such as "nano-flowers...

Ultrasmall nanoparticles (USNPs) are attracting an increasing interest for a variety of biomedical applications, from therapeutic targeting to imaging, in virtue of the peculiar behavior shown in vivo (i.e. efficient renal clearance, low liver accumulation etc.). In evaluating their potential to overcome some of the challenges that larger particles...

Salcaprozate sodium (SNAC) and sodium caprate (C10) are the two leading intestinal permeation enhancers (PEs) in oral peptide formulations in clinical trials. There is debate over their mechanism of action on intestinal epithelia. The aims were: (i) to compare their effects on the barrier function by measuring transepithelial electrical resistance...

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 plat...

We know surprisingly little about the long-term outcomes for nanomaterials interacting with organisms. To date, most of what we know is derived from in vivo studies that limit the range of materials studied, and the scope of advanced molecular biology tools applied. Long-term in vitro nanoparticle studies are hampered by a lack of suitable models,...

Characterisation and Categorisation Strategies for Anisotropic Gold Nanoparticles for Applications in Biology - Volume 25 Supplement - Jennifer Cookman, João. M. de Araujo, Kenneth A. Dawson

Magnetic separation is a promising alternative to conventional methods in downstream processing. This can facilitate easier handling, fewer processing steps, and more sustainable processes. Target materials can be extracted directly from crude cell lysates in a single step by magnetic nanoadsorbents with high-gradient magnetic fishing (HGMF). Addit...

The temporal context of cell death decisions remains generally hidden in ensemble measurements with endpoint readouts. Here, we describe a method to extract event times from fluorescence time traces of cell death-related markers in automated live-cell imaging on single-cell arrays (LISCA) using epithelial A549 lung and Huh7 liver cancer cells as a...

The biological interactions of graphene have been extensively investigated over the last 10 years. However, very little is known about graphene interactions with the cell surface and how the graphene internalization process is driven and mediated by specific recognition sites at the interface with the cell. In this work, we propose a methodology to...

INDUCTION OF EPIGENETIC RESPONSE TO AMINO-MODIFIED POLYSTYRENE NANOPARTICLES IN HUMAN CELLS Miglena Koprinarova, David Garry�, Delyan R. Hristov�, Ivanka Dimova��, Kenneth A. Dawson� (Submitted by Corresponding Member O. Poljakova-Krusteva on March 20, 2017) Abstract Amino-modified nanoparticles have a toxic effect on the mammalian cells. Their asp...

The systematic study of nanoparticle-biological interactions requires particles to be reproducibly dispersed in relevant fluids along with further development in the identification of biologically relevant structural details at the materials-biology interface. Here, we develop a biocompatible long-term colloidally stable water dispersion of few-lay...

Key practical challenges such as to understand the immunological processes at the nanoscale, and to control the targeting and accumulation of nano-objects in vivo now further stimulate efforts to underpin phenomenological knowledge of the nanoscale with more mechanistic and molecular insight. Thus, the question as to what constitutes nanoscale biol...

Surface patterning colloidal matter in the sub-10 nm regime generates exceptional functionality in biology, photonic and electronic materials. Techniques to artificially generate functional patterns in the small nanoscale advanced fascinatingly in the last years, however, remain often restricted to planar and non-colloidal substrates. Patterning co...

Here we present a method for the rapid screening of exposed protein recognition motifs on the surface of nanoparticles exploiting quartz crystal microbalance (QCM). We quantify accessible functional epitopes of transferrin-coated nanoparticles and correlate them to differences in nanoparticle size and functionalization. The target recognition occur...

Silver nanoparticles were grown in aqueous solution, without the presence of typical surfactant molecules, but under the presence of different proteins. The shape of the resulting silver nanoparticles could be tuned by the selection of the types of proteins. The amount of accessible lysine groups was found to be mainly responsible for the anisotrop...

Manufactured nanomaterials (MNMs) selected from a library of over 120 different MNMs with varied compositions, sizes, and surface coatings were tested by four different laboratories for toxicity by high-throughput/-content (HT/C) techniques. The selected particles comprise 14 MNMs composed of CeO2, Ag, TiO2, ZnO and SiO2 with different coatings and...

In biological fluids, proteins and other biomolecules bind to the surface of nanoparticles to form a coating known as the protein corona which in turn becomes primary determinant of the nanoparticles’ fate and behaviour. Here we develop a QCM-based platform and methodology to obtain data from real-time interactions of nanoparticles with selected hu...

Nanoparticles have great potential as drug delivery vehicles or as imaging agents for treatment and diagnosis of various diseases. It is therefore crucial to understand how nanoparticles are taken up by cells, both phagocytic and non-phagocytic. Small interference RNA has previously been used to isolate the effect of particular receptors in nanopar...

Cellular barriers, such as the skin, the lung epithelium or the intestinal epithelium, constitute one of the first obstacles facing nanomedicines or other nanoparticles entering organisms. It is thus important to assess the capacity of nanoparticles to enter and transport across such barriers. In this work, Caco-2 intestinal epithelial cells were u...

Supplementary methods and figures.

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 w...

The potential release of nanoparticles (NPs) into aquatic environments represents a growing concern for their possible impact on aquatic organisms. In this light, exposure studies during early life stages, which can be highly sensitive to environmental perturbations, would greatly help identifying potential adverse effects of NPs. Although in the m...

Plastic pollution has been globally recognized as a critical issue for marine ecosystems and nanoplastics constitute one of the last unexplored areas to understand the magnitude of this threat. However, current difficulties in sampling and identifying nano-sized debris make hard to assess their occurrence in marine environment. Polystyrene nanopart...

Most inhaled nanomedicines in development are for the treatment of lung disease, yet little is known about their interaction with the respiratory tract lining fluids (RTLF). Here we combined the use of nano-silica, as a protein concentrator, with label-free snapshot proteomics (LC-MS/MS; key findings confirmed by ELISA) to generate a quantitative p...

SiRNA is a promising molecule for gene therapy, but its therapeutic administration remains problematic. Among the recently proposed vectors, cell-penetrating peptides show great promise in in vivo trials for siRNA delivery. The human protein DMBT1 is a pattern recognition molecule that interacts with polyanions and recognizes and aggregates bacteri...

The transport and the delivery of drugs through nanocarriers is a great challenge of pharmacology. Since the production of liposomes to reduce the toxicity of doxorubicin in patients, a plethora of nanomaterials have been produced and characterized. Although it is widely known that elementary properties of nanomaterials influence their in vivo kine...

Nanoparticles (NPs) are often functionalized with reactive groups like amines or thiols for the subsequent conjugation of further molecules, e.g., stabilizing polymers, drugs and proteins for targeting cells or specific diseases, etc. In addition to the quantitative estimation of the reactive conjugation sites, their molecular positioning and nanos...

Supplementary

The shape and size of nanoparticles are important parameters affecting the biodistribution, bioactivity, and toxicity. The high-throughput characterisation of nanoparticle shape in the dispersion is a fundamental prerequisite for realistic in vitro and in vivo evaluation, however, with routinely available bench-top optical characterisation techniqu...

http://www.tandfonline.com/eprint/rFbz3XMTtVBrQvCaHPZW/full Polystyrene nanoparticles have been shown to pose serious risk to marine organisms including sea urchin embryos based on their surface properties and consequently behaviour in natural sea water. The aim of this study is to investigate the toxicity pathways of amino polystyrene nanoparticl...

Biomolecules adsorbed on nanoparticles are known to confer a biological identity to nanoparticles, mediating the interactions with cells and biological barriers. However, how these molecules are presented on the particle surface in biological milieu remains unclear. The central aim of this study is to identify key protein recognition motifs and lin...

Characterizing the orientation of covalently conjugated proteins on nanoparticles, produced for in vitro and in vivo targeting, though an important feature of such a system, has proved challenging. Although extensive physicochemical characterization of targeting nanoparticles can be addressed in detail, relevant biological characterzation of the na...

Characterizing the orientation of covalently conjugated proteins on nanoparticles, produced for in vitro and in vivo targeting, though an important feature of such a system, has proved challenging. Although extensive physicochemical characterization of targeting nanoparticles can be addressed in detail, relevant biological characterization of the n...

The nanoscale is the “natural” scale of many key elements of biology and biological function. Cells barriers and organs function, signal, communicate, and transfer materials using active nanoscale processes fueled by the cellular energy and rarely involve diffusive motion. Nanoparticles, initially recognized will often be accumulated in the degrada...

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 prope...

Nanoparticles interacting with, or derived from, living organisms are almost invariably coated in a variety of biomolecules presented in complex biological milieu, which produce a bio-interface or biomolecular corona' conferring a biological identity to the particle. Biomolecules at the surface of the nanoparticle-biomolecule complex present molecu...

Supplementary Figures 1-27, Supplementary Tables 1-3 and Supplementary References

When a pristine nanoparticle (NP) encounters a biological fluid, biomolecules spontaneously form adsorption layers around the NP, called "protein corona". The corona composition depends on the time-dependent environmental conditions and determines the NP's fate within living organisms. Understanding how the corona evolves is fundamental in nanotoxi...

It has been well established that the early stages of nanoparticle-cell interactions are governed, at least in part, by the layer of proteins and other biomolecules adsorbed and slowly exchanging with the surrounding biological media (biomolecular corona). Subsequent to membrane interactions, nanoparticles are typically internalized into the cell a...

Nanoparticles (NPs) functionalized with two active targeting ligands have been proposed in drug delivery for their promising capability to stimulate different pathways with one object. Due to the multivalency, the construction and analysis of the effective surface of such bifunctional nanoparticles, however, is significantly more complex than for n...

Experimental observations in cell biology have advanced to a stage where theory could play a larger role, much as it has done in the physical sciences. Possibly the lack of a common framework within which experimentalists, computational scientists and theorists could equally contribute has hindered this development, for the worse of both discipline...

Random covalent conjugation of targeting moieties is currently the most common strategy to synthesize nanomaterials for biological applications. Two aspects play a key role in nanoparticle-cell predetermined receptor specific interaction, specifically favorable surface density and accessibility. However, often the actual surface landscape and funct...

Despite many investigations have focused on the pristine toxicity of gold nanoparticles (GNPs), little is known about the outcome of co-exposure and interaction of GNPs with heavy metals which can possibly detoxify or potentiate them. Here, the combined exposure of nickel (II) sulphate (NiSO4) and GNPs on the maturation response of dendritic cells...

Synthetic nanoparticles are promising tools for imaging and drug delivery; however the molecular details of cellular internalization and trafficking await full characterization. Current knowledge suggests that following endocytosis most nanoparticles pass from endosomes to lysosomes. In order to design effective drug delivery strategies that can us...

Observing structural integrity of nanoparticles is essential in bionanotechnology but not always straightforward to measure in situ and in real-time. Fluorescent labels used for tracking intrinsically non-fluorescent nanomaterials generally do not allow simultaneous observation of integrity. Consequently, structural changes like degradation and dis...

Polymeric microbubbles (MBs) are gas filled particles composed of a thin stabilized polymer shell that have been recently developed as valid contrast agents for the combined use of ultrasonography (US), magnetic resonance imaging (MRI) and single photon emission computer tomography (SPECT) imaging. Due to their buoyancy, the commonly available appr...

Unlabelled: When inhaled nanoparticles deposit in the lungs, they transit through respiratory tract lining fluid (RTLF) acquiring a biomolecular corona reflecting the interaction of the RTLF with the nanomaterial surface. Label-free snapshot proteomics was used to generate semi-quantitative profiles of corona proteins formed around silica (SiO2) a...