It is possible to steer placental uptake and penetration of AuNPs by tailoring their properties, which is a prerequisite for the development of targeted therapies in pregnancy.
To better study the impact of nanoparticles on both in vitro and in vivo models, tissue distribution and cellular doses need to be described more closely. Here silver nanoparticles were visualized in alveolar macrophages by means of synchrotron radiation micro X-ray fluorescence spectroscopy (SR-μXRF) with high spatial resolution of 3 × 3 μm 2 . For the spatial allocation of silver signals to cells and tissue structures, additional elemental labeling was carried out by staining with eosin, which binds to protein and can be detected as bromine signal with SR-μXRF. The method was compatible with immunostaining of macrophage antigens. We found that the silver distribution obtained with SR-μXRF was largely congruent with distribution maps from a subsequent laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) of the same tissue sites. The study shows a predominant, though not exclusive uptake of silver into alveolar macrophages in the rat lung, which can be modeled by a similar uptake in cultured alveolar macrophages. Advantages and limitations of the different strategies for measuring nanoparticle uptake at the single cell level are discussed.
BackgroundThe well-known inflammatory and fibrogenic changes of the lung upon crystalline silica are accompanied by early changes of the phospholipid composition (PLC) as detected in broncho-alveolar lavage fluid (BALF). Amorphous silica nanoparticles (NPs) evoke transient lung inflammation, but their effect on PLC is unknown. Here, we compared effects of unmodified and phosphonated amorphous silica NP and describe, for the first time, local changes of the PLC with innovative bioimaging tools.MethodsUnmodified (SiO2-n), 3-(trihydroxysilyl) propyl methylphosphonate coated SiO2-n (SiO2-p) as well as a fluorescent surrogate of SiO2-n (SiO2-FITC) nanoparticles were used in this study. In vitro toxicity was tested with NR8383 alveolar macrophages. Rats were intratracheally instilled with SiO2-n, SiO2-p, or SiO2-FITC, and effects on lungs were analyzed after 3 days. BALF from the right lung was analyzed for inflammatory markers. Cryo-sections of the left lung were subjected to fluorescence microscopy and PLC analyses by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MS), Fourier transform infrared microspectroscopy (FT-IR), and tandem mass spectrometry (MS/MS) experiments.ResultsCompared to SiO2-p, SiO2-n NPs were more cytotoxic to macrophages in vitro and more inflammatory in the rat lung, as reflected by increased concentration of neutrophils and protein in BALF. Fluorescence microscopy revealed a typical patchy distribution of SiO2-FITC located within the lung parenchyma and alveolar macrophages. Superimposable to this particle distribution, SiO2-FITC elicited local increases of phosphatidylglycerol (PG) and phosphatidylinositol (PI), whereas phoshatidylserine (PS) and signals from triacylgyceride (TAG) were decreased in the same areas. No such changes were found in lungs treated with SiO2-p or particle-free instillation fluid.ConclusionsPhosphonate coating mitigates effects of silica NP in the lung and abolishes their locally induced changes in PLC pattern. Bioimaging methods based on MALDI-MS may become a useful tool to investigate the mode of action of NPs in tissues.Electronic supplementary materialThe online version of this article (10.1186/s12989-018-0267-z) contains supplementary material, which is available to authorized users.
Correction for ‘Quantitative imaging of translocated silver following nanoparticle exposure by laser ablation-inductively coupled plasma-mass spectrometry’ by David P. Bishop et al., Anal. Methods, 2018, DOI: 10.1039/c7ay02294h.
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