Hollow-fiber flow field-flow fractionation and multi-angle light scattering investigation of the size, shape and metal-release of silver nanoparticles in aqueous medium for nano-risk assessment

open11siAvailable online 22 November 2014 The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007–2013) through the project SANOWORK under Grant Agreement no. 280716. The HRTEM has been made available under the INSPIRE programme, funded by Irish Government's Programme for Research in Third Level Institutions, Cycle 4, National Development Plan 2007–2013, which is supported by European Union Structural Fund. Drs. Abbasi Gandhi and Vishnu Mogili of the University of Limerick are acknowledged for generating HRTEM data.Due to the increased use of silver nanoparticles in industrial scale manufacturing, consumer products and nanomedicine reliable measurements of properties such as the size, shape and distribution of these nano particles in aqueous medium is critical. These properties indeed affect both functional properties and biological impacts especially in quantifying associated risks and identifying suitable risk-mediation strategies. The feasibility of on-line coupling of a fractionation technique such as hollow-fiber flow field flow fractionation (HF5) with a light scattering technique such as MALS (multi-angle light scattering) is investigated here for this purpose. Data obtained from such a fractionation technique and its combination thereof with MALS have been compared with those from more conventional but often complementary techniques e.g. transmission electron microscopy, dynamic light scattering, atomic absorption spectroscopy, and X-ray fluorescence. The combination of fractionation and multi angle light scattering techniques have been found to offer an ideal, hyphenated methodology for a simultaneous size-separation and characterization of silver nanoparticles. The hydrodynamic radii determined by fractionation techniques can be conveniently correlated to the mean average diameters determined by multi angle light scattering and reliable information on particle morphology in aqueous dispersion has been obtained. The ability to separate silver (Ag+) ions from silver nanoparticles (AgNPs) via membrane filtration during size analysis is an added advantage in obtaining quantitative insights to its risk potential. Most importantly, the methodology developed in this article can potentially be extended to similar characterization of metal-based nanoparticles when studying their functional effectiveness and hazard potential.partially_openembargoed_20151122Marassi, Valentina; Casolari, Sonia; Roda, Barbara; Zattoni, Andrea; Reschiglian, Pierluigi; Panzavolta, Silvia; Tofail, Syed A.M.; Ortelli, Simona; Delpivo, Camilla; Blosi, Magda; Costa, Anna LuisaMarassi, Valentina; Casolari, Sonia; Roda, Barbara; Zattoni, Andrea; Reschiglian, Pierluigi; Panzavolta, Silvia; Tofail, Syed A.M.; Ortelli, Simona; Delpivo, Camilla; Blosi, Magda; Costa, Anna Luis

Ground-breaking new medical alloy with higher x-ray visibility to improve patient treatment worldwide

Since the 1990s therapeutic procedures using catheters, stents and other minimally invasive medical devices have replaced the need for invasive surgical procedures of the past. However, many of these devices are made of metal alloys which are difficult to see during treatment. The Materials and Surface Science Institute (MSSI) at the University of Limerick has invented a new alloy that overcomes this difficulty. Medical devices made from this new alloy will be highly visible under medical x-ray imaging, making placement, manipulation and application inside the body much easier. This will significantly improve treatment quality by reducing time required for treatment, repeat procedures, and trauma. In addition to impacting patients, the project has significantly increased medical R&D capacity in Ireland and helped provide highly skilled jobs in both research and manufacturing. The research was conducted by UL in partnership with international medical devices company Cook Medical, and was supported by Enterprise Ireland

Static magnetic susceptibility of radiopaque NiTiPt and NiTiEr

Magnetic properties of metallic alloys used in biomedical industry are important for the magnetic resonance imaging (MRI). If the alloys were to be used for long term implants or as guiding devices, safety of the patient as well as the medical staff has to be ensured. Strong response to the external magnetic field can cause mechanical damage to the patients body. In this paper we present magnetic susceptibility of nickel rich, ternary NiTiPt and NiTiEr to static magnetic field. We show that the magnetic susceptibility of these radiopaque alloys has values in low paramagnetic region comparable to the binary nickel-titanium. Furthermore, we studied the effect of the ther mal and mechanical treatments on magnetic properties. Despite deviation from linear M(H) treated samples spanning small region around H = 0, the linearity of the M(H) and x = dM=dH values suggest that these ternary alloys are safe to use under MRI conditions

The effects of a varied gold shell thickness on iron oxide nanoparticle cores in magnetic manipulation, T1 and T2 MRI contrasting, and magnetic hyperthermia

Fe3O4–Au core–shell magnetic-plasmonic nanoparticles are expected to combine both magnetic and light responsivity into a single nanosystem, facilitating combined optical and magnetic-based nanotheranostic (therapeutic and diagnostic) applications, for example, photothermal therapy in conjunction with magnetic resonance imaging (MRI) imaging. To date, the effects of a plasmonic gold shell on an iron oxide nanoparticle core in magnetic-based applications remains largely unexplored. For this study, we quantified the efficacy of magnetic iron oxide cores with various gold shell thicknesses in a number of popular magnetic-based nanotheranostic applications; these included magnetic sorting and targeting (quantifying magnetic manipulability and magnetophoresis), MRI contrasting (quantifying benchtop nuclear magnetic resonance (NMR)-based T1 and T2 relaxivity), and magnetic hyperthermia therapy (quantifying alternating magnetic-field heating). We observed a general decrease in magnetic response and efficacy with an increase of the gold shell thickness, and herein we discuss possible reasons for this reduction. The magnetophoresis speed of iron oxide nanoparticles coated with the thickest gold shell tested here (ca. 42 nm) was only ca. 1% of the non-coated bare magnetic nanoparticle, demonstrating reduced magnetic manipulability. The T1 relaxivity, r1, of the thick gold-shelled magnetic particle was ca. 22% of the purely magnetic counterpart, whereas the T2 relaxivity, r2, was 42%, indicating a reduced MRI contrasting. Lastly, the magnetic hyperthermia heating efficiency (intrinsic loss power parameter) was reduced to ca. 14% for the thickest gold shell. For all applications, the efficiency decayed exponentially with increased gold shell thickness; therefore, if the primary application of the nanostructure is magnetic-based, this work suggests that it is preferable to use a thinner gold shell or higher levels of stimuli to compensate for losses associated with the addition of the gold shell. Moreover, as thinner gold shells have better magnetic properties, have previously demonstrated superior optical properties, and are more economical than thick gold shells, it can be said that “less is more”

Tantalum coating inhibits Ni-migration from titanium out-diffusion in NiTi shape memory biomedical alloy

Despite the presence of over 56% Ni by weight, equiatomic NiTi is generally considered biocompatible as it naturally oxidises to form a surface oxide mainly composed of biocompatible oxides of titanium (TiOx). This layer is formed by an oxidation mechanism that promotes out-diffusion of Ti leaving a Ti-depleted, Ni rich subsurface.The long-term in vivo stability of the naturally grown Ti Oxlayer has been a concern as Ni can leach out through this thin, defective layer. The leaching of nickel (Ni) is thus a continuing threat to the alloy’s other wise outstanding bio compatibility. We have found that a layer of reactively sputtered tantalum(Ta)oxide on the bulk NiTi restricts Ti-out-migration through a biocompatible Ti/Tainter-diffusion layer that provides a larger barrier against Ni leaching. We have investigated this inter-diffusion as a function of sputtering process parameters and post processing treatments. Surface and interface analytical techniques such as X-ray photoelectron spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, cross sectional transmission electron microscopy and non-destructive ion beam analysis techniques such as Rutherford backscattering spectrometry and particle induced X-ray emission were used to evaluate the nature of this interdiffusion layer which can improve long-term biocompatibility of NiT

Electrochemical biosensor for the detection of a sequence of the TP53 gene using a methylene blue labelled DNA probe#

The development of an electrochemical biosensor utilising a hairpin DNA probe labelled with methylene blue for the detection of the TP53 gene is described. Structural rearrangement of the hairpin probe into a linear double DNA strand induced different rates of electron transfer that enabled an increase in current upon hybridization. The increase in current observed upon hybridization was studied at different surface probe densities, hybridization times, concentration and length of target DNA sequences. The biosensor selectively detected a single nucleotide polymorphism in the TP53 gene affecting residue 175 of the p53 protein, with the response more pronounced at shorter hybridization times. Detection of target DNA sequences at nanomolar concentrations was achieved and the sensor possessed good operational and storage stabilit

Pathway complexity in supramolecular porphyrin self-assembly at an immiscible liquid–liquid interface

Nanostructures that are inaccessible through spontaneous thermodynamic processes may be formed by supramolecular self-assembly under kinetic control. In the past decade, the dynamics of pathway complexity in self-assembly have been elucidated through kinetic models based on aggregate growth by sequential monomer association and dissociation. Immiscible liquid−liquid interfaces are an attractive platform to develop well-ordered self-assembled nanostructures, unattainable in bulk solution, due to the templating interaction of the interface with adsorbed molecules. Here, we report time resolved in situ UV−vis spectroscopic observations of the self-assembly of zinc(II) meso-tetrakis(4-carboxyphenyl)porphyrin (ZnTPPc) at an immiscible aqueous−organic interface. We show that the kinetically favored metastable J-type nanostructures form quickly, but then transform into stable thermodynamically favored H-type nanostructures. Numerical modeling revealed two parallel and competing cooperative pathways leading to the different porphyrin nanostructures. These insights demonstrate that pathway complexity is not unique to self-assembly processes in bulk solution and is equally valid for interfacial self-assembly. Subsequently, the interfacial electrostatic environment was tuned using a kosmotropic anion (citrate) in order to influence the pathway selection. At high concentrations, interfacial nanostructure formation was forced completely down the kinetically favored pathway, and only J-type nanostructures were obtained. Furthermore, we found by atomic force microscopy and scanning electron microscopy that the J- and H-type nanostructures obtained at low and high citric acid concentrations, respectively, are morphologically distinct, which illustrates the pathway-dependent material properties

MRI guided magneto-chemotherapy with high-magnetic-moment iron oxide nanoparticles for cancer theranostics

Elevating and monitoring the temperature of tumors using magnetic nanoparticles (MNPs) still presents a challenge in magnetic hyperthermia therapy. The efficient heating of tumor volume can be achieved by preparing MNPs with high magnetization values. The next-generation approach to magnetic resonance image (MRI)-guided magneto-chemotherapy of cancer based on high-magnetic-moment iron oxide nanoparticles is proposed. The proof of concept is validated by cellular MRI experiments on breast cancer cells. To explore magneto-chemotherapy, we developed high-magnetic-moment iron oxide (Fe3O4) nanoparticles (NPs) using base diisopropylamine (DIPA), which plays a dual role as reducing agent and surface stabilizer. Spherical NPs with ∼12 nm size and a high magnetization value of about 92 emu g–1 at room temperature are obtained by this unique method. A high specific absorption rate value of ∼717 wg–1 was obtained for Fe3O4 NPs in water at an alternating magnetic field of 20 kAm–1 and frequency of 267 kHz, which is attributed to the high magnetization value. The magneto-polymeric micelle structure is formed by using Pluronic F127, and anticancer drug doxorubicin is conjugated in the micelle by electrostatic interactions for magneto-chemotherapy. Finally, the magnetic resonance imaging (MRI)-guided magneto-chemotherapy was achieved on breast cancer (MCF7) cells with an overall ∼96% killing of cancer cells attained in 30 min of magneto-chmeotherapy

Empowering citizens in international governance of nanotechnologies

The international dialogue on responsible governance of nanotechnologies engages a wide range of actors with conflicting as well as common interests. It is also characterised by a lack of evidence-based data on uncertain risks of in particular engineered nanomaterials. The present paper aims at deepening understanding of the collective decision making context at international level using the grounded theory approach as proposed by Glaser and Strauss in "The Discovery of Grounded Theory\u27\u27 (1967). This starts by discussing relevant concepts from different fields including sociological and political studies of international relations as well as political philosophy and ethics. This analysis of current trends in international law making is taken as starting point for exploring the role that a software decision support tool could play in multi-stakeholder global governance of nanotechnologies. These theoretical ideas are then compared with the current design of the SUN Decision Support System (SUNDS) under development in the European project on Sustainable Nanotechnologies (SUN, www.sun-fp7.eu). Through constant comparison, the ideas are also compared with requirements of different stakeholders as expressed during a user workshop. This allows for highlighting discussion points for further consideration.PUBLISHEDpeer-reviewe