The antibacterial action of silver is utilized in numerous consumer products and medical devices. Metallic silver, silver salts, and also silver nanoparticles are used for this purpose. The state of research on the effect of silver on bacteria, cells, and higher organisms is summarized. It can be concluded that the therapeutic window for silver is narrower than often assumed. However, the risks for humans and the environment are probably limited.

Silver as Antibacterial Agent: Ion, Nanoparticle, and Metal

In vivo imaging, which enables us to peer deeply within living subjects, is producing tremendous opportunities both for clinical diagnostics and as a research tool. Contrast material is often required to clearly visualize the functional architecture of physiological structures. Recent advances in nanomaterials are becoming pivotal to generate the high-resolution, high-contrast images needed for accurate, precision diagnostics. Nanomaterials are playing major roles in imaging by delivering large imaging payloads, yielding improved sensitivity, multiplexing capacity, and modularity of design. Indeed, for several imaging modalities, nanomaterials are now not simply ancillary contrast entities, but are instead the original and sole source of image signal that make possible the modality’s existence. We address the physicochemical makeup/design of nanomaterials through the lens of the physical properties that produce contrast signal for the cognate imaging modality—we stratify nanomaterials on the basis of thei...

Nanomaterials for In Vivo Imaging

Nanoparticles (NPs) are of similar size to typical cellular components and proteins, and can efficiently intrude living cells. A detailed understanding of the involved processes at the molecular level is important for developing NPs designed for selective uptake by specific cells, for example, for targeted drug delivery. In addition, this knowledge can greatly assist in the engineering of NPs that should not penetrate cells so as to avoid adverse health effects. In recent years, a wide variety of experiments have been performed to elucidate the mechanisms underlying cellular NP uptake. Here, we review some select recent studies, which are often based on fluorescence microscopy and sophisticated strategies for specific labelling of key cellular components. We address the role of the protein corona forming around NPs in biological environments, and describe recent work revealing active endocytosis mechanisms and pathways involved in their cellular uptake. Passive uptake is also discussed. The current state of knowledge is summarized, and we point to issues that still need to be addressed to further advance our understanding of cellular NP uptake.

https://royalsocietypublishing.org/doi/pdf/10.1098/rsif.2012.0939

New views on cellular uptake and trafficking of manufactured nanoparticles

The environmental soot and carbon blacks cause many diseases in humans but their underlying mechanisms of toxicity are still poorly understood. Both are formed after the incomplete combustion of hydrocarbons but differ in their constituents and percent carbon contents. For the first time, “Sir Percival Pott” described soot as a carcinogen, which was subsequently confirmed by many others. The existing data suggests three main types of diseases due to soot and carbon black exposures; cancer, respiratory diseases and cardiovascular dysfunctions. Experimental models revealed the involvement of oxidative stress, DNA methylation, formation of DNA adducts and Aryl hydrocarbon receptor (AhR) activation as the key mechanisms of soot and carbon black induced cancers. Metals including Si, Fe, Mn, Ti, and Co in soot also contribute in the reactive oxygen species (ROS) mediated DNA damage. Mechanistically, ROS induced DNA damage is further enhanced by eosinophils and neutrophils via halide (Cl- and Br-) dependent DNA adducts formation. The activation of pulmonary dendritic cells, T helper type 2 cells and mast cells are crucial mediators in the pathology of soot or carbon black induced respiratory disease. Polyunsaturated fatty acids (PUFA) were also found to modulate T cells functions in respiratory diseases. Particularly, telomerase reverse transcriptase was found to play the critical role in soot and carbon black induced cardiovascular dysfunctions. In this review, we propose integrated mechanisms of soot and carbon black induced toxicity emphasizing the role of inflammatory mediators and oxidative stress. We also suggest use of antioxidants and polyunsaturated fatty acids as protective strategies against soot and carbon black induced disorders.

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The Toxicological Mechanisms of Environmental Soot (Black Carbon) and Carbon Black: Focus on Oxidative Stress and Inflammatory Pathways

The detection techniques used in biosensors can be broadly classified into label-based and label-free. Label-based detection relies on the specific properties of labels for detecting a particular target. In contrast, label-free detection is suitable for the target molecules that are not labeled or the screening of analytes which are not easy to tag. Also, more types of label-free biosensors have emerged with developments in biotechnology. The latest developed techniques in label-free biosensors, such as field-effect transistors-based biosensors including carbon nanotube field-effect transistor biosensors, graphene field-effect transistor biosensors and silicon nanowire field-effect transistor biosensors, magnetoelastic biosensors, optical-based biosensors, surface stress-based biosensors and other type of biosensors based on the nanotechnology are discussed. The sensing principles, configurations, sensing performance, applications, advantages and restriction of different label-free based biosensor...

Progress of new label-free techniques for biosensors: a review.

We present in this article an outline of some cyclotron-based irradiation techniques that can be used to directly radiolabel industrially manufactured nanoparticles, as well as two techniques for synthesis of labelled nanoparticles using cyclotron-generated radioactive precursor materials. These radiolabelled nanoparticles are suitable for a range of different in vitro and in vivo tracing studies of relevance to the field of nanotoxicology. A basic overview is given of the relevant physics of nuclear reactions regarding both ion-beam and neutron production of radioisotopes. The various issues that determine the practicality and usefulness of the different methods are discussed, including radioisotope yield, nuclear reaction kinetics, radiation and thermal damage, and radiolabel stability. Experimental details are presented regarding several techniques applied in our laboratories, including direct light-ion activation of dry nanoparticle samples, neutron activation of nanoparticles and suspensions using an ion-beam driven activator, spark-ignition generation of nanoparticle aerosols using activated electrode materials, and radiochemical synthesis of nanoparticles using cyclotron-produced isotopes. The application of these techniques is illustrated through short descriptions of some selected results thus far achieved. It is shown that these cyclotron-based methods offer a very useful range of options for nanoparticle radiolabelling despite some experimental difficulties associated with their application. For direct nanoparticle radiolabelling, if care is taken in choosing the experimental conditions applied, useful activity levels can be achieved in a wide range of nanoparticle types, without causing substantial thermal or radiation damage to the nanoparticle structure. Nanoparticle synthesis using radioactive precursors presents a different set of issues and offers a complementary and equally valid approach when laboratory generation of the nanoparticles is acceptable for the proposed studies, and where an appropriate radiolabel can be incorporated into the nanoparticles during synthesis.

Radiolabelling of engineered nanoparticles for in vitro and in vivo tracing applications using cyclotron accelerators

{sup 44} is a promising {beta}{sup +}-emitter for molecular imaging with intermediate half-life of 4 h. Due to the chemical similarity of Sc{sup 3+} to the Lu{sup 3+} and Y{sup 3+} cations, {sup 44}Sc-DOTA bioconjugates are expected to demonstrate similar properties in vivo as the {sup 177}Lu- and {sup 90}Y-bioconjugates, what is important in planning the radionuclide therapy. {sup 44}Sc can be obtained from the {sup 44}Ti/{sup 44}Sc generator. An alternative method for {sup 44}Sc production can be the irradiation of {sup 44}Ca target at small cyclotrons. The aim of our work was to optimize the parameters of {sup 44}CaCO{sub 3} irradiation and to develop a simple procedure for {sup 44}Sc separation from the calcium target. For optimization study, {sup 44}CaCO{sub 3} targets were irradiated by protons in the energy range of 5.6-17.5 MeV with 9 MeV being found to be the best energy for {sup 44}Ca irradiations. A simple and fast separation procedure of {sup 44}Sc from calcium target was developed using chelating resin Chelex 100. DOTATATE conjugate was successfully radiolabelled with high yield at elevated temperature using the produced {sup 44}Sc. While {sup 44}CaCO{sub 3} is relatively expensive, the cost of {sup 44}Sc-DOTATATE production can be reduced by target recovery. Due to low proton energy required to produce GBq activity level of {sup 44}Sc, the availability of {sup 44}Sc radioisotope could be enhanced to open new opportunities for applications in medical imaging. (orig.)

Cyclotron production of 44Sc for clinical application

Industrially manufactured titanium dioxide nanoparticles have been successfully radiolabelled with 48V by irradiation with a cyclotron-generated proton beam. Centrifugation tests showed that the 48V radiolabels were stably bound within the nanoparticle structure in an aqueous medium, while X-ray diffraction indicated that no major structural modifications to the nanoparticles resulted from the proton irradiation. In vitro tests of the uptake of cold and radiolabelled nanoparticles using the human cell line Calu-3 showed no significant difference in the uptake between both batches of nanoparticles. The uptake was quantified by Inductively Coupled Plasma Mass Spectrometry and high resolution γ-ray spectrometry for cold and radiolabelled nanoparticles, respectively. These preliminary results indicate that alterations to the nanoparticles’ properties introduced by proton bombardment can be controlled to a sufficient extent that their further use as radiotracers for biological investigations can be envisaged and elaborated.

/pdf/radiolabelling-of-tio2-nanoparticles-for-radiotracer-studies-2f50lp71ny.pdf

Radiolabelling of TiO2 nanoparticles for radiotracer studies

Radiolabelled nanoparticles are useful tools for biodistribution or cellular uptake studies related to the risk assessment of nanomaterials. Such studies are ideally carried out with industrially manufactured nanoparticles. Irradiation of small quantities of such nanoparticles, in the form of dry powders, with neutrons or light ions allows radiolabelling while preserving their biologically relevant properties. However, nanoparticle powders exhibit poor thermal conductivity and may overheat under irradiation. Their effective thermal conductivity is not known and conventional temperature measurement methods are difficult to apply. Reasonably accurate temperature data could be derived from post-irradiation X-ray diffraction studies on anatase ST-01 TiO2-nanoparticles, with a primary particle size of 7 nm, subjected to proton beams of different intensities. The anatase-to-rutile phase transition starting at about 750 °C was identified by observing rutile peaks in X-ray diffraction patterns. The onset of growth of single diffracting TiO2-domains at around 200 °C was revealed by shape analysis of the diffraction peaks. Identifying these reference temperatures allowed a calibration of the calculated temperature profile. The effective thermal conductivity in the TiO2 powder target was found to be close to that of air trapped in interstices of the nanoparticulate powder. This suggests that the contribution of the nanoparticles to the heat removal from the target is negligible, thus necessitating the use of thin nanoparticle layers in the target in order to facilitate cooling and prevent thermally induced alterations of the nanoparticles.

Radiolabelling of nanoparticles by proton irradiation: temperature control in nanoparticulate powder targets

The current global crisis in supply of the medical isotope generator 99Mo/99mTc has triggered much research into alternative non-reactor based production methods for 99Mo including innovative radionuclide production techniques using ion accelerators A novel method is presented here that has thus far not been considered: 232Th is used as target material to produce carrier-free 99Mo for 99Mo/99mTc generators by proton-induced fission (232Th (p, f) 99Mo) The thick target yields of 99Mo are estimated as 36 MBq/μA·h and 21 MBq/μA·h for proton energies of 22 MeV and 40 MeV, respectively, energies that are available from many cyclotrons With respect to 99Mo reactor based methods using uranium targets, the presented concept using 232Th does not pose proliferation concerns, transport of highly radioactive target materials can be reduced and unused cyclotron capacities could be exploited Radiochemical target processing could be based on existing technologies of extraction of 99Mo from reactor irradiated 235U The presented method could be used for co-production of other radioisotopes of medical interest such as 131I

I. Cydzik

Papers

Radiolabelling of engineered nanoparticles for in vitro and in vivo tracing applications using cyclotron accelerators

Cyclotron production of 44Sc for clinical application

Radiolabelling of TiO2 nanoparticles for radiotracer studies

Radiolabelling of nanoparticles by proton irradiation: temperature control in nanoparticulate powder targets

Feasibility of 99Mo production by proton-induced fission of 232Th