RESUMO
Despite its crucial role, the placenta is the least understood human organ. Recent clinical studies indicate a direct association between placental calcification and maternal and offspring health. This study reveals distinct characteristics of minerals formed during gestational ageing using cutting-edge nano-analytical characterization and paves the way for investigations focused on the identification of potential markers for disease risks in a clinical setting based on atypical placental mineral fingerprints.
Assuntos
Calcificação Fisiológica/fisiologia , Minerais/análise , Placenta/metabolismo , Animais , Gatos , Cães , Feminino , Cavalos , Humanos , Microscopia Eletrônica de Varredura , Minerais/química , Minerais/metabolismo , Placenta/ultraestrutura , Gravidez , Coelhos , Análise Espectral , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Gold nanoparticles (AuNPs) are promising candidates to design the next generation NP-based drug formulations specifically treating maternal, fetal or placental complications with reduced side effects. Profound knowledge on AuNP distribution and effects at the human placental barrier in dependence on the particle properties and surface modifications, however, is currently lacking. Moreover, the predictive value of human placental transfer models for NP translocation studies is not yet clearly understood, in particular with regards to differences between static and dynamic exposures. To understand if small (3-4 nm) AuNPs with different surface modifications (PEGylated versus carboxylated) are taken up and cross the human placental barrier, we performed translocation studies in a static human in vitro co-culture placenta model and the dynamic human ex vivo placental perfusion model. The samples were analysed using ICP-MS, laser ablation-ICP-MS and TEM analysis for sensitive, label-free detection of AuNPs. RESULTS: After 24 h of exposure, both AuNP types crossed the human placental barrier in vitro, although in low amounts. Even though cellular uptake was higher for carboxylated AuNPs, translocation was slightly increased for PEGylated AuNPs. After 6 h of perfusion, only PEGylated AuNPs were observed in the fetal circulation and tissue accumulation was similar for both AuNP types. While PEGylated AuNPs were highly stable in the biological media and provided consistent results among the two placenta models, carboxylated AuNPs agglomerated and adhered to the perfusion device, resulting in different cellular doses under static and dynamic exposure conditions. CONCLUSIONS: Gold nanoparticles cross the human placental barrier in limited amounts and accumulate in placental tissue, depending on their size- and/or surface modification. However, it is challenging to identify the contribution of individual characteristics since they often affect colloidal particle stability, resulting in different biological interaction in particular under static versus dynamic conditions. This study highlights that human ex vivo and in vitro placenta models can provide valuable mechanistic insights on NP uptake and translocation if accounting for NP stability and non-specific interactions with the test system.
Assuntos
Ouro/química , Nanopartículas Metálicas/química , Modelos Biológicos , Placenta/metabolismo , Linhagem Celular , Técnicas de Cocultura , Coloides/química , Feminino , Humanos , Cinética , Perfusão , Gravidez , Distribuição TecidualRESUMO
In a dual approach, laser ablation-inductively coupled plasma-mass spectrometry was applied to investigate spleen samples of rats after intratracheal instillation of polyvinylpyrrolidone-coated gold nanoparticles. First, spatially resolved imaging analysis was deployed to investigate gold translocation from the lungs to the spleen and to investigate the distribution pattern of gold in the spleen parenchyma itself. Using the same instrumental setup, laser ablation-inductively coupled plasma-mass spectrometry in single particle mode was applied to determine the species of translocated gold. Single particle analysis allows the determination of particle size distributions and therefore to distinguish between ionic species, intact nanoparticles, and agglomerates. A translocation of instilled gold from the lungs to the spleen was demonstrated for gold nanoparticles of 30 and 50 nm diameter. Furthermore single particle analysis revealed the translocation of intact gold nanoparticles in a non-agglomerated state.
Assuntos
Ouro/química , Terapia a Laser/métodos , Espectrometria de Massas/métodos , Nanopartículas Metálicas/administração & dosagem , Baço/metabolismo , Traqueia/efeitos dos fármacos , Animais , Feminino , Injeção Intratimpânica , Nanopartículas Metálicas/química , Tamanho da Partícula , Ratos , Ratos Wistar , Análise Espacial , Baço/efeitos dos fármacosRESUMO
Total mercury (THg) and monomethylmercury (MMHg) concentrations as well as mercury (Hg) isotope ratios were determined in sediment cores sampled from six locations from the Canadian Arctic Archipelago (CAA). At most sites, THg concentrations showed a decreasing trend with depth, ranging from 5 to 61â¯ng/g, implicating possible increased Hg deposition and/or riverine inputs in top sediment layers. MMHg values showed large oscillations within the top 10â¯cm of the cores. This variability decreased at the bottom of the cores with MMHg concentrations ranging from less than12 to up to 1073â¯pg/g. Average concentrations of THg and MMHg in the top 10â¯cm were linearly correlated, whereas no correlation was observed with organic matter (loss on ignition). Mercury isotope ratios showed negative values for both δ202Hg (-1.59 to -0.55) and Δ199Hg (-0.62 to -0.01). δ202Hg values became more negative with depth, while the opposite was observed for Δ199Hg. The former is consistent with predicted historical atmospheric Hg trends as a result of increased coal burning worldwide. Hg isotope ratio measurements in CAA sediments offer additional opportunities to trace Hg processes and sources in the Arctic.
RESUMO
HYPOTHESIS: Gold nanoparticles (GNP) are considered an ideal model to help understanding the nano-skin interface. The surface functionality of gold nanorods (GNR) is expected to influence the uptake of nanoparticles into specific targets of skin such as hair follicles or dermis. Hence, it should be possible to modify the surface chemistry of GNP to achieve more targeted and safe skin therapy. EXPERIMENTS: GNR functionalized with various surface ligands (neutral, anionic, cationic, and hydrophobic) were evaluated for their accumulation into hair follicles of human skin sheets using ex-vivo setup. The extent of GNR accumulation into hair follicles and other skin compartments was quantified by inductively coupled plasma-optical emission spectroscopy (ICP-OES), and their spatial distribution through skin layers was investigated by laser ablation-inductively coupled plasma-mass spectroscopy (LA-ICP-MS). RESULTS: The lipophilic properties of sebum-rich hair follicles enhanced the accumulation of hydrophobic polystyrene (PS)-GNR into hair follicles (â¼13% of the total applied dose), while neutral polyethylene glycol (PEG)-GNR were distributed into all skin compartments, especially the dermis (â¼11.5% of the total applied dose), which exhibits hydrophilic characteristics. Charged GNR showed a negligible percentage of penetration into any of the skin compartments. GNR could be a promising approach for targeted skin disease treatment and transdermal administration of drugs and therapy.
Assuntos
Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Ouro/química , Ouro/farmacocinética , Folículo Piloso/metabolismo , Nanotubos/química , Resinas Acrílicas/química , Resinas Acrílicas/farmacocinética , Adulto , Sistemas de Liberação de Medicamentos , Humanos , Ligantes , Masculino , Nanotubos/ultraestrutura , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Poliestirenos/química , Poliestirenos/farmacocinética , Pele/metabolismo , Absorção Cutânea , Propriedades de SuperfícieRESUMO
A liver biopsy specimen from a Wilson's disease (WD) patient was analyzed by means of micro-X-ray fluorescence (µXRF) spectroscopy to determine the elemental distribution. First, bench-top µXRF was utilized for a coarse scan of the sample under laboratory conditions. The resulting distribution maps of copper and iron enabled the determination of a region of interest (ROI) for further analysis. In order to obtain more detailed elemental information, this ROI was analyzed by synchrotron radiation (SR)-based µXRF with a beam size of 4 µm offering a resolution at the cellular level. Distribution maps of additional elements to copper and iron like zinc and manganese were obtained due to a higher sensitivity of SR-µXRF. In addition to this, X-ray absorption near edge structure spectroscopy (XANES) was performed to identify the oxidation states of copper in WD. This speciation analysis indicated a mixture of copper(i) and copper(ii) within the WD liver tissue.