Biodistribution of cerium dioxide and titanium dioxide nanomaterials in rats after single and repeated inhalation exposures.

BACKGROUND: Physiologically based kinetic models facilitate the safety assessment of inhaled engineered nanomaterials (ENMs). To develop these models, high quality datasets on well-characterized ENMs are needed. However, there are at present, several data gaps in the systemic availability of poorly soluble particles after inhalation. The aim of the present study was therefore to acquire two comparable datasets to parametrize a physiologically-based kinetic model. METHOD: Rats were exposed to cerium dioxide (CeO2, 28.4 ± 10.4 nm) and titanium dioxide (TiO2, 21.6 ± 1.5 nm) ENMs in a single nose-only exposure to 20 mg/m3 or a repeated exposure of 2 × 5 days to 5 mg/m3. Different dose levels were obtained by varying the exposure time for 30 min, 2 or 6 h per day. The content of cerium or titanium in three compartments of the lung (tissue, epithelial lining fluid and freely moving cells), mediastinal lymph nodes, liver, spleen, kidney, blood and excreta was measured by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) at various time points post-exposure. As biodistribution is best studied at sub-toxic dose levels, lactate dehydrogenase (LDH), total protein, total cell numbers and differential cell counts were determined in bronchoalveolar lavage fluid (BALF). RESULTS: Although similar lung deposited doses were obtained for both materials, exposure to CeO2 induced persistent inflammation indicated by neutrophil granulocytes influx and exhibited an increased lung elimination half-time, while exposure to TiO2 did not. The lavaged lung tissue contained the highest metal concentration compared to the lavage fluid and cells in the lavage fluid for both materials. Increased cerium concentrations above control levels in secondary organs such as lymph nodes, liver, spleen, kidney, urine and faeces were detected, while for titanium this was found in lymph nodes and liver after repeated exposure and in blood and faeces after a single exposure. CONCLUSION: We have provided insight in the distribution kinetics of these two ENMs based on experimental data and modelling. The study design allows extrapolation at different dose-levels and study durations. Despite equal dose levels of both ENMs, we observed different distribution patterns, that, in part may be explained by subtle differences in biological responses in the lung.

Effect of ultra-high-density polyethylene microplastic on the sorption and biodegradation of organic micropollutants.

Microplastics and organic micropollutants are two emerging contaminants that interact with each other in environmental and engineered systems. Sorption of organic micropollutants, such as pharmaceuticals, pesticides and industrial compounds, to microplastics can modify their bioavailability and biodegradation. The present study investigated the capacity of ultra-high density polyethylene particles (125 µm in diameter), before and after aging, to sorb 21 organic micropollutants at different environmentally relevant concentration. Furthermore, the biodegradation of these organic micropollutants by a biofilm microbial community growing on the microplastic surface was compared with the biodegradation by a microbial community originating from activated sludge. Among all tested organic micropollutants, propranolol (70%), trimethoprim (25%) and sotalol (15%) were sorbed in the presence of polyethylene particles. Growth of a biofilm on the polyethylene particles had a beneficial effect on the sorption of bromoxynil, caffeine and chloridazon and on the biodegradation of irbesartan, atenolol and benzotriazole. On the other hand, the biofilm limited the sorption of trimethoprim, propranolol, sotalol and benzotriazole and the biodegradation of 2,4-D. These results showed that ultra-high density polyethylene particles can affect both in a positive and negative way for the abiotic and biotic removal of organic micropollutants in wastewater. This project highlights the need for further investigation regarding the interaction between microplastics and organic micropollutants in the aquatic environment.

Safety of recycled plastics and textiles: Review on the detection, identification and safety assessment of contaminants.

In 2019, 368 mln tonnes of plastics were produced worldwide. Likewise, the textiles and apparel industry, with an annual revenue of 1.3 trillion USD in 2016, is one of the largest fast-growing industries. Sustainable use of resources forces the development of new plastic and textile recycling methods and implementation of the circular economy (reduce, reuse and recycle) concept. However, circular use of plastics and textiles could lead to the accumulation of a variety of contaminants in the recycled product. This paper first reviewed the origin and nature of potential hazards that arise from recycling processes of plastics and textiles. Next, we reviewed current analytical methods and safety assessment frameworks that could be adapted to detect and identify these contaminants. Various contaminants can end up in recycled plastic. Phthalates are formed during waste collection while flame retardants and heavy metals are introduced during the recycling process. Contaminants linked to textile recycling include; detergents, resistant coatings, flame retardants, plastics coatings, antibacterial and anti-mould agents, pesticides, dyes, volatile organic compounds and nanomaterials. However, information is limited and further research is required. Various techniques are available that have detected various compounds, However, standards have to be developed in order to identify these compounds. Furthermore, the techniques mentioned in this review cover a wide range of organic chemicals, but studies covering potential inorganic contamination in recycled materials are still missing. Finally, approaches like TTC and CoMSAS for risk assessment should be used for recycled plastic and textile materials.

Issues currently complicating the risk assessment of synthetic amorphous silica (SAS) nanoparticles after oral exposure.

Synthetic amorphous silica (SAS) is applied in food products as food additive E 551. It consists of constituent amorphous silicon dioxide (SiO2) nanoparticles that form aggregates and agglomerates. We reviewed recent oral toxicity studies with SAS. Some of those report tissue concentrations of silicon (Si). The results of those studies were compared with recently determined tissue concentrations of Si (and Si-particles) in human postmortem tissues. We noticed inconsistent results of the various toxicity studies regarding toxicity and reported tissue concentrations, which hamper the risk assessment of SAS. A broad range of Si concentrations is reported in control animals in toxicity studies. The Si concentrations found in human postmortem tissues fall within this range. On the other hand, the mean concentration found in human liver is higher than the reported concentrations causing liver effects in some animal toxicity studies after oral exposure to SAS. Also higher liver concentrations are observed in other, negative animal studies. Those inconsistencies could be caused by the presence of other Si-containing chemical substances or particles (which potentially also includes background SAS) and/or different sample preparation and analytical techniques that were used. Other factors which could explain the inconsistencies in outcome between the toxicity studies are the distinct SAS used and different dosing regimes, such as way of administration (dietary, via drinking water, oral gavage), dispersion of SAS and dose. More research is needed to address these issues and to perform a proper risk assessment for SAS in food. The current review will help to progress research on the toxicity of SAS and the associated risk assessment.

Nanoparticle Tracking Analysis of Gold Nanoparticles in Aqueous Media through an Inter-Laboratory Comparison.

In the field of nanotechnology, analytical characterization plays a vital role in understanding the behavior and toxicity of nanomaterials (NMs). Characterization needs to be thorough and the technique chosen should be well-suited to the property to be determined, the material being analyzed and the medium in which it is present. Furthermore, the instrument operation and methodology need to be well-developed and clearly understood by the user to avoid data collection errors. Any discrepancies in the applied method or procedure can lead to differences and poor reproducibility of obtained data. This paper aims to clarify the method to measure the hydrodynamic diameter of gold nanoparticles by means of Nanoparticle Tracking Analysis (NTA). This study was carried out as an inter-laboratory comparison (ILC) amongst seven different laboratories to validate the standard operating procedure's performance and reproducibility. The results obtained from this ILC study reveal the importance and benefits of detailed standard operating procedures (SOPs), best practice updates, user knowledge, and measurement automation.

Experimental Flight Patterns Evaluation for a UAV-Based Air Pollutant Sensor.

The use of drones in combination with remote sensors have displayed increasing interest over the last years due to its potential to automate monitoring processes. In this study, a novel approach of a small flying e-nose is proposed by assembling a set of AlphaSense electrochemical-sensors to a DJI Matrix 100 unmanned aerial vehicle (UAV). The system was tested on an outdoor field with a source of NO2. Field tests were conducted in a 100 m2 area on two dates with different wind speed levels varying from low (0.0-2.9m/s) to high (2.1-5.3m/s), two flight patterns zigzag and spiral and at three altitudes (3, 6 and 9 m). The objective of this study is to evaluate the sensors responsiveness and performance when subject to distinct flying conditions. A Wilcoxon rank-sum test showed significant difference between flight patterns only under High Wind conditions, with Spiral flights being slightly superior than Zigzag. With the aim of contributing to other studies in the same field, the data used in this analysis will be shared with the scientific community.

Possible effects of titanium dioxide particles on human liver, intestinal tissue, spleen and kidney after oral exposure.

Recent studies reported adverse liver effects and intestinal tumor formation after oral exposure to titanium dioxide (TiO2). Other oral toxicological studies, however, observed no effects on liver and intestine, despite prolonged exposure and/or high doses. In the present assessment, we aimed to better understand whether TiO2 can induce such effects at conditions relevant for humans. Therefore, we focused not only on the clinical and histopathological observations, but also used Adverse Outcome Pathways (AOPs) to consider earlier steps (Key Events). In addition, aiming for a more accurate risk assessment, the available information on organ concentrations of Ti (resulting from exposure to TiO2) from oral animal studies was compared to recently reported concentrations found in human postmortem organs. The overview obtained with the AOP approach indicates that TiO2 can trigger a number of key events in liver and intestine: Reactive Oxygen Species (ROS) generation, induction of oxidative stress and inflammation. TiO2 seems to be able to exert these early effects in animal studies at Ti liver concentrations that are only a factor of 30 and 6 times higher than the median and highest liver concentration found in humans, respectively. This confirms earlier conclusions that adverse effects on the liver in humans as a result of (oral) TiO2 exposure cannot be excluded. Data for comparison with Ti levels in human intestinal tissue, spleen and kidney with effect concentrations were too limited to draw firm conclusions. The Ti levels, though, are similar or higher than those found in liver, suggesting these tissues may be relevant too.

In vitro and in vivo study on the osseointegration of BCP-coated versus uncoated nondegradable thermoplastic polyurethane focal knee resurfacing implants.

Focal knee resurfacing implants (FKRIs) are intended to treat cartilage defects in middle-aged patients. Most FKRIs are metal-based, which hampers follow-up of the joint using magnetic resonance imaging and potentially leads to damage of the opposing cartilage. The purpose of this study was to develop a nondegradable thermoplastic polyurethane (TPU) FKRI and investigate its osseointegration. Different surface roughness modifications and biphasic calcium phosphate (BCP) coating densities were first tested in vitro on TPU discs. The in vivo osseointegration of BCP-coated TPU implants was subsequently compared to uncoated TPU implants and the titanium bottom layer of metal control implants in a caprine model. Implants were implanted bilaterally in stifle joints and animals were followed for 12 weeks, after which the bone-to-implant contact area (BIC) was assessed. Additionally, 18F-sodium-fluoride (18F-NaF) positron emission tomography PET/CT-scans were obtained at 3 and 12 weeks to visualize the bone metabolism over time. The BIC was significantly higher for the BCP-coated TPU implants compared to the uncoated TPU implants (p = .03), and did not significantly differ from titanium (p = .68). Similar 18F-NaF tracer uptake patterns were observed between 3 and 12 weeks for the BCP-coated TPU and titanium implants, but not for the uncoated implants. TPU FKRIs with surface modifications could provide the answer to the drawbacks of metal FKRIs.

Combination of the BeWo b30 placental transport model and the embryonic stem cell test to assess the potential developmental toxicity of silver nanoparticles.

BACKGROUND: Silver nanoparticles (AgNPs) are used extensively in various consumer products because of their antimicrobial potential. This requires insight in their potential hazards and risks including adverse effects during pregnancy on the developing fetus. Using a combination of the BeWo b30 placental transport model and the mouse embryonic stem cell test (EST), we investigated the capability of pristine AgNPs with different surface chemistries and aged AgNPs (silver sulfide (Ag2S) NPs) to cross the placental barrier and induce developmental toxicity. The uptake/association and transport of AgNPs through the BeWo b30 was characterized using ICP-MS and single particle (sp)ICP-MS at different time points. The developmental toxicity of the AgNPs was investigated by characterizing their potential to inhibit the differentiation of mouse embryonic stem cells (mESCs) into beating cardiomyocytes. RESULTS: The AgNPs are able to cross the BeWo b30 cell layer to a level that was limited and dependent on their surface chemistry. In the EST, no in vitro developmental toxicity was observed as the effects on differentiation of the mESCs were only detected at cytotoxic concentrations. The aged AgNPs were significantly less cytotoxic, less bioavailable and did not induce developmental toxicity. CONCLUSIONS: Pristine AgNPs are capable to cross the placental barrier to an extent that is influenced by their surface chemistry and that this transport is likely low but not negligible. Next to that, the tested AgNPs have low intrinsic potencies for developmental toxicity. The combination of the BeWo b30 model with the EST is of added value in developmental toxicity screening and prioritization of AgNPs.

Current Insights into Monitoring, Bioaccumulation, and Potential Health Effects of Microplastics Present in the Food Chain.

Microplastics (MPs) are considered an emerging issue as environmental pollutants and a potential health threat. This review will focus on recently published data on concentrations in food, possible effects, and monitoring methods. Some data are available on concentrations in seafood (fish, bivalves, and shrimps), water, sugar, salt, and honey, but are lacking for other foods. Bottled water is a considerable source with numbers varying between 2600 and 6300 MPs per liter. Particle size distributions have revealed an abundance of particles smaller than 25 µm, which are considered to have the highest probability to pass the intestinal border and to enter the systemic circulation of mammals. Some studies with mice and zebrafish with short- or medium-term exposure (up to 42 days) have revealed diverse results with respect to both the type and extent of effects. Most notable modifications have been observed in gut microbiota, lipid metabolism, and oxidative stress. The principal elements of MP monitoring in food are sample preparation, detection, and identification. Identified data gaps include a lack of occurrence data in plant- and animal-derived food, a need for more data on possible effects of different types of microplastics, a lack of in silico models, a lack of harmonized monitoring methods, and a further development of quality assurance.

Silicon dioxide and titanium dioxide particles found in human tissues.

Silicon dioxide (silica, SiO2, SAS) and titanium dioxide (TiO2) are produced in high volumes and applied in many consumer and food products. As a consequence, there is a potential human exposure and subsequent systemic uptake of these particles. In this study we show the characterization and quantification of both total silicon (Si) and titanium (Ti), and particulate SiO2 and TiO2 in postmortem tissue samples from 15 deceased persons. Included tissues are liver, spleen, kidney and the intestinal tissues jejunum and ileum. Low-level analysis was enabled by the use of fully validated sample digestion methods combined with (single particle) inductively coupled plasma high resolution mass spectrometry techniques (spICP-HRMS). The results show a total-Si concentration ranging from <2 to 191 mg Si/kg (median values of 5.8 (liver), 9.5 (spleen), 7.7 (kidney), 6.8 (jejunum), 7.6 (ileum) mg Si/kg) while the particulate SiO2 ranged from <0.2 to 25 mg Si/kg (median values of 0.4 (liver), 1.0 (spleen), 0.4 (kidney), 0.7 (jejunum, 0.6 (ileum) mg Si/kg), explaining about 10% of the total-Si concentration. Particle sizes ranged from 150 to 850 nm with a mode of 270 nm. For total-Ti the results show concentrations ranging from <0.01 to 2.0 mg Ti/kg (median values of 0.02 (liver), 0.04 (spleen), 0.05 (kidney), 0.13 (jejunum), 0.26 (ileum) mg Ti/kg) while particulate TiO2 concentrations ranged from 0.01 to 1.8 mg Ti/kg (median values of 0.02 (liver), 0.02 (spleen), 0.03 (kidney), 0.08 (jejunum), 0.25 (ileum) mg Ti/kg). In general, the particulate TiO2 explained 80% of the total-Ti concentration. This indicates that most Ti in these organ tissues is particulate material. The detected particles comprise primary particles, aggregates and agglomerates, and were in the range of 50-500 nm with a mode in the range of 100-160 nm. About 17% of the detected TiO2 particles had a size <100 nm. The presence of SiO2 and TiO2 particles in liver tissue was confirmed by scanning electron microscopy with energy dispersive X-ray spectrometry.

Impact of in vitro digestion on gastrointestinal fate and uptake of silver nanoparticles with different surface modifications.

Nanomaterials, especially silver nanoparticles (AgNPs), are used in a broad range of products owing to their antimicrobial potential. Oral ingestion is considered as a main exposure route to AgNPs. This study aimed to investigate the impact of the biochemical conditions within the human digestive tract on the intestinal fate of AgNPs across an intestinal in vitro model of differentiated Caco-2/HT29-MTX cells. The co-culture model was exposed to different concentrations (250-2500 µg/L) of pristine and in vitro digested (IVD) AgNPs and silver nitrate for 24 h. ICP-MS and spICP-MS measurements were performed for quantification of total Ag and AgNPs. The AgNPs size distribution, dissolution, and particle concentration (mass- and number-based) were characterized in the cell fraction and in the apical and basolateral compartments of the monolayer cultures. A significant fraction of the AgNPs dissolved (86-92% and 48-70%) during the digestion. Cellular exposure to increasing concentrations of pristine or IVD AgNPs resulted in a concentration dependent increase of total Ag and AgNPs content in the cellular fractions. The cellular concentrations were significantly lower following exposure to IVD AgNPs compared to the pristine AgNPs. Transport of silver as either total Ag or AgNPs was limited (<0.1%) following exposure to pristine and IVD AgNPs. We conclude that the surface chemistry of AgNPs and their digestion influence their dissolution properties, uptake/association with the Caco-2/HT29-MTX monolayer. This highlights the need to take in vitro digestion into account when studying nanoparticle toxicokinetics and toxicodynamics in cellular in vitro model systems.

Brominated flame retardants in animal derived foods in the Netherlands between 2009 and 2014.

Polybrominated diphenylethers (PBDEs), hexabromocyclododecanes (HBCDDs) and tetrabromobisphenol A (TBBPA) were monitored in various foods from terrestrial and aquatic animal origin (>850 samples), collected in the Netherlands between 2009 and 2014. The terrestrial samples included meat/fat from 7 animal species (including bovines, pigs, broilers and sheep), bovine milk and hen eggs. Dominant PBDE congeners in these samples were BDE-47, -99, -100, -153 and -183. The meat/fat generally contained the highest ∑PBDE concentrations compared to eggs and milk, with meat from deer, horse and sheep containing the highest concentrations. Generally declining ∑PBDE concentrations were observed between 2009 and 2014, however, this was only significant in pig meat and hen's eggs. The aquatic samples included fillets from 18 species (including herring, haddock and salmon), brown crab parts, shrimp and mussels, and the highest ∑PBDE concentrations were seen in body parts of brown crab, herring, mackerel, salmon and sea bass (on wet weight basis). Patterns generally contained more congeners (i.e., BDE-28, -49 and -66) additional to the aforementioned congeners found in terrestrial samples. Herring, sea bass and brown crab (body parts) contained among the highest PBDE concentrations. TBBPA was only detected in 3 individual samples (bovine and broiler meat and haddock), while α-HBCDD was the dominant diastereomer detected in several terrestrial and aquatic samples. When detected, TBBPA and HBCDD concentrations were generally in the same order as ∑PBDE concentrations in the same sample types.

Detection of nanoparticles in Dutch surface waters.

Nano-enabled consumer products are a likely source of nanoparticles in the environment and a number of studies have shown the release of nanoparticles from commercial products. Predicted environmental concentrations have been calculated but there is a need for real measurement data to validate these calculations. However, the detection of engineered nanoparticles in environmental matrices is challenging because of the low predicted environmental concentrations which may be in the ng/L range. In this study nanosized Ag, CeO2 and TiO2 have been measured in multiple surface water samples collected along the rivers Meuse and IJssel in the Netherlands using single-particle ICP-MS as measurement technique. Validation of the analytical method showed its capability to quantitatively determine nanoparticles at low concentrations. Concentration mass detection limits for Ag, CeO2 and TiO2 were 0.1ng/L, 0.05ng/L and 10ng/L respectively. Size detection limits for Ag, CeO2 and TiO2 were 14, 10 and 100nm. The results of the study confirm the presence of nano-sized Ag and CeO2 particles and micro-sized TiO2 particles in these surface waters. n-Ag was present in all samples in concentrations ranging from 0.3 to 2.5ng/L with an average concentration of 0.8ng/L and an average particle size of 15nm. n-CeO2 was found in all samples with concentrations ranging from 0.4 to 5.2ng/L with an average concentration of 2.7ng/L and an average particle size of 19nm. Finally, µ-TiO2 was found in all samples with a concentration ranging from 0.2 to 8.1µg/L with an average concentration of 3.1µg/L and an average particle size of 300nm. The particle sizes that were found are comparable with the particle sizes that are used in nanomaterial applications and consumer products. The nanoparticle concentrations confirm the predicted environmental concentrations values in water for all three nanoparticles.

Evaluation of dextran(ethylene glycol) hydrogel films for giant unilamellar lipid vesicle production and their application for the encapsulation of polymersomes.

Giant Unilamellar Vesicles (GUVs) prepared from phospholipids are becoming popular membrane model systems for use in biophysical studies. The quality, size and yield of GUVs depend on the preparation method used to obtain them. In this study, hydrogels consisting of dextran polymers crosslinked by poly(ethylene glycol) (DexPEG) were used as hydrophilic frameworks for the preparation of vesicle suspensions under physiological ionic strength conditions. A comparative study was conducted using hydrogels with varied physicochemical properties to evaluate their performance for GUV production. The prepared GUVs were quantified by flow cytometry using the Coulter Principle to determine the yield and size distribution. We find that hydrogels of lower mechanical strength, increased swellability and decreased lipid interaction favour GUV production, while their resulting size is determined by the surface roughness of the hydrogel film. Moreover, we embedded polymersomes into the crosslinked hydrogel network, creating a DexPEG - polymersome hybrid film. The re-hydration of lipids on those hybrid substrates led to the production of GUVs and the efficient encapsulation of polymersomes in the lumen of GUVs.

Transport of silver nanoparticles by runoff and erosion - A flume experiment.

Silver nanoparticles (AgNPs) are being used in many products as they have unique antimicrobial-biocidal properties. After disposal of these products AgNPs can reach the soil environment possibly affecting soil organisms and disrupting plants. This work aimed to study the transport of AgNPs by water and sediment during overland flow and soil erosion. This was done in a laboratory setting, using a flume and rainfall simulator. A low concentration of AgNPs (50µg·kg-1) was applied to two soil-flumes with slope percentages of 20% and 10%. The rainfall was applied in four events of 15min each with a total amount of rainfall of 15mm during each event. After applying the rainfall, samples of the non-transported background soil (BS) and the transported sediment (Sf) were collected from the flume surface. Runoff sediment (RS) and water (RW) were collected from the outlet. AgNPs were detected in all samples collected. However, concentration varied according to sample type (soil or water), time of collection (for runoff water and sediment) and the slope of the soil flume. Higher concentrations of AgNPs in soil were detected in the BS than in the Sf likely due to the BS having more fine particles (silt and clay). The AgNPs concentration in the runoff sediments increased with subsequent applied rain events. In addition, increasing the slope of the flume from 10% to 20% increased the total AgNPs transported with the runoff sediment by a factor 1.5. The study confirms that AgNPs can be transported by both overland flow and sediment due to erosion.

Hybrid Imaging Labels: Providing the Link Between Mass Spectrometry-Based Molecular Pathology and Theranostics.

BACKGROUND: Development of theranostic concepts that include inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) imaging can be hindered by the lack of a direct comparison to more standardly used methods for in vitro and in vivo evaluation; e.g. fluorescence or nuclear medicine. In this study a bimodal (or rather, hybrid) tracer that contains both a fluorescent dye and a chelate was used to evaluate the existence of a direct link between mass spectrometry (MS) and in vitro and in vivo molecular imaging findings using fluorescence and radioisotopes. At the same time, the hybrid label was used to determine whether the use of a single isotope label would allow for MS-based diagnostics. METHODS: A hybrid label that contained both a DTPA chelate (that was coordinated with either 165Ho or 111In) and a Cy5 fluorescent dye was coupled to the chemokine receptor 4 (CXCR4) targeting peptide Ac-TZ14011 (hybrid-Cy5-Ac-TZ4011). This receptor targeting tracer was used to 1) validate the efficacy of (165Ho-based) mass-cytometry in determining the receptor affinity via comparison with fluorescence-based flow cytometry (Cy5), 2) evaluate the microscopic binding pattern of the tracer in tumor cells using both fluorescence confocal imaging (Cy5) and LA-ICP-MS-imaging (165Ho), 3) compare in vivo biodistribution patterns obtained with ICP-MS (165Ho) and radiodetection (111In) after intravenous administration of hybrid-Cy5-Ac-TZ4011 in tumor-bearing mice. Finally, LA-ICP-MS-imaging (165Ho) was linked to fluorescence-based analysis of excised tissue samples (Cy5). RESULTS: Analysis with both mass-cytometry and flow cytometry revealed a similar receptor affinity, respectively 352 ± 141 nM and 245 ± 65 nM (p = 0.08), but with a much lower detection sensitivity for the first modality. In vitro LA-ICP-MS imaging (165Ho) enabled clear discrimination between CXCR4 positive and negative cells, but fluorescence microscopy was required to determine the intracellular distribution. In vivo biodistribution patterns obtained with ICP-MS (165Ho) and radiodetection (111In) of the hybrid peptide were shown to be similar. Assessment of tracer distribution in excised tissues revealed the location of tracer uptake with both LA-ICP-MS-imaging and fluorescence imaging. CONCLUSION: Lanthanide-isotope chelation expands the scope of fluorescent/radioactive hybrid tracers to include MS-based analytical tools such as mass-cytometry, ICP-MS and LA-ICP-MS imaging in molecular pathology. In contradiction to common expectations, MS detection using a single chelate imaging agent was shown to be feasible, enabling a direct link between nuclear medicine-based imaging and theranostic methods.

Different responses of Caco-2 and MCF-7 cells to silver nanoparticles are based on highly similar mechanisms of action.

The mode of action of silver nanoparticles (AgNPs) is suggested to be exerted through both Ag+ and AgNP dependent mechanisms. Ingestion is one of the major NP exposure routes, and potential effects are often studied using Caco-2 cells, a well-established model for the gut epithelium. MCF-7 cells are epithelial breast cancer cells with extensive well-characterized toxicogenomics profiles. In the present study, we aimed to gain a deeper understanding of the cellular molecular responses in Caco-2 and MCF-7 cells after AgNP exposure in order to evaluate whether epithelial cells derived from different tissues demonstrated similar responses. These insights could possibly reduce the size of cell panels for NP hazard identification screening purposes. AgNPs of 20, 30, 60, and 110 nm, and AgNO3 were exposed for 6 h and 24 h. AgNPs were shown to be taken up and dissolve intracellularly. Compared with MCF-7 cells, Caco-2 cells showed a higher sensitivity to AgNPs, slower gene expression kinetics and absence of NP size-dependent responses. However, on a molecular level, no significant differences were observed between the two cell types. Transcriptomic analysis showed that Ag(NP) exposure caused (oxidative) stress responses, possibly leading to cell death in both cell lines. There was no indication for effects specifically induced by AgNPs. Responses to AgNPs appeared to be induced by silver ions released from the AgNPs. In conclusion, differences in mRNA responses to AgNPs between Caco-2 and MCF-7 cells were mainly related to timing and magnitude, but not to a different underlying mechanism.

Physicochemical characterization of titanium dioxide pigments using various techniques for size determination and asymmetric flow field flow fractionation hyphenated with inductively coupled plasma mass spectrometry.

Seven commercial titanium dioxide pigments and two other well-defined TiO2 materials (TiMs) were physicochemically characterised using asymmetric flow field flow fractionation (aF4) for separation, various techniques to determine size distribution and inductively coupled plasma mass spectrometry (ICPMS) for chemical characterization. The aF4-ICPMS conditions were optimised and validated for linearity, limit of detection, recovery, repeatability and reproducibility, all indicating good performance. Multi-element detection with aF4-ICPMS showed that some commercial pigments contained zirconium co-eluting with titanium in aF4. The other two TiMs, NM103 and NM104, contained aluminium as integral part of the titanium peak eluting in aF4. The materials were characterised using various size determination techniques: retention time in aF4, aF4 hyphenated with multi-angle laser light spectrometry (MALS), single particle ICPMS (spICPMS), scanning electron microscopy (SEM) and particle tracking analysis (PTA). PTA appeared inappropriate. For the other techniques, size distribution patterns were quite similar, i.e. high polydispersity with diameters from 20 to >700 nm, a modal peak between 200 and 500 nm and a shoulder at 600 nm. Number-based size distribution techniques as spICPMS and SEM showed smaller modal diameters than aF4-UV, from which mass-based diameters are calculated. With aF4-MALS calculated, light-scattering-based "diameters of gyration" (Øg) are similar to hydrodynamic diameters (Øh) from aF4-UV analyses and diameters observed with SEM, but much larger than with spICPMS. A Øg/Øh ratio of about 1 indicates that the TiMs are oblate spheres or fractal aggregates. SEM observations confirm the latter structure. The rationale for differences in modal peak diameter is discussed.

Polymers in Cartilage Defect Repair of the Knee: Current Status and Future Prospects.

Cartilage defects in the knee are often seen in young and active patients. There is a need for effective joint preserving treatments in patients suffering from cartilage defects, as untreated defects often lead to osteoarthritis. Within the last two decades, tissue engineering based techniques using a wide variety of polymers, cell sources, and signaling molecules have been evaluated. We start this review with basic background information on cartilage structure, its intrinsic repair, and an overview of the cartilage repair treatments from a historical perspective. Next, we thoroughly discuss polymer construct components and their current use in commercially available constructs. Finally, we provide an in-depth discussion about construct considerations such as degradation rates, cell sources, mechanical properties, joint homeostasis, and non-degradable/hybrid resurfacing techniques. As future prospects in cartilage repair, we foresee developments in three areas: first, further optimization of degradable scaffolds towards more biomimetic grafts and improved joint environment. Second, we predict that patient-specific non-degradable resurfacing implants will become increasingly applied and will provide a feasible treatment for older patients or failed regenerative treatments. Third, we foresee an increase of interest in hybrid construct, which combines degradable with non-degradable materials.