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Silver nanoparticles do not alter human osteoclastogenesis but induce cellular uptake.

ABSTRACT: Based on the increasing number of multi-drug resistant bacteria in periprosthetic infections, improvement of the antibacterial activity of commonly used biomaterials must be achieved. The broad-spectrum, high antimicrobial efficacy has made silver nanoparticles a promising new antibacterial agent. However, there is still a serious lack of knowledge concerning the impact of nanosilver on bone cells. For this reason a study was conducted to evaluate the influence of silver nanoparticles on osteoclastogenesis of human peripheral blood mononuclear cells. Upon incubation with subtoxic concentrations of nanosilver the cells did not exhibit changes in osteoclast differentiation and podosomal structures. However, the osteoclasts were able to uptake the nanoparticles, accumulating them in endo-lysosomal compartments. Furthermore, nanosilver exposure led to an increase in oxidative stress and a decrease in clathrin-dependent endocytosis on the mRNA level. In conclusion, our results indicate nanosilver-induced cell stress at higher concentrations. For this reason antibacterial benefits and possible health risks should be weighed in more detail in further studies.

SUBMITTER: Pauksch L

PROVIDER: S-EPMC5598169 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Silver nanoparticles do not alter human osteoclastogenesis but induce cellular uptake.

Pauksch Linda L Rohnke Marcus M Schnettler Reinhard R Lips Katrin S KS

Toxicology reports 20141018

Based on the increasing number of multi-drug resistant bacteria in periprosthetic infections, improvement of the antibacterial activity of commonly used biomaterials must be achieved. The broad-spectrum, high antimicrobial efficacy has made silver nanoparticles a promising new antibacterial agent. However, there is still a serious lack of knowledge concerning the impact of nanosilver on bone cells. For this reason a study was conducted to evaluate the influence of silver nanoparticles on osteocl ...[more]

PMID: 28962302

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Project description:BackgroundSilver nanoparticles (AgNPs) are currently one of the most manufactured nanomaterials. A wide range of toxicity studies have been performed on various AgNPs, but these studies report a high variation in toxicity and often lack proper particle characterization. The aim of this study was to investigate size- and coating-dependent toxicity of thoroughly characterized AgNPs following exposure of human lung cells and to explore the mechanisms of toxicity.MethodsBEAS-2B cells were exposed to citrate coated AgNPs of different primary particle sizes (10, 40 and 75 nm) as well as to 10 nm PVP coated and 50 nm uncoated AgNPs. The particle agglomeration in cell medium was investigated by photon cross correlation spectroscopy (PCCS); cell viability by LDH and Alamar Blue assay; ROS induction by DCFH-DA assay; genotoxicity by alkaline comet assay and γH2AX foci formation; uptake and intracellular localization by transmission electron microscopy (TEM); and cellular dose as well as Ag release by atomic absorption spectroscopy (AAS).ResultsThe results showed cytotoxicity only of the 10 nm particles independent of surface coating. In contrast, all AgNPs tested caused an increase in overall DNA damage after 24 h assessed by the comet assay, suggesting independent mechanisms for cytotoxicity and DNA damage. However, there was no γH2AX foci formation and no increased production of intracellular reactive oxygen species (ROS). The reasons for the higher toxicity of the 10 nm particles were explored by investigating particle agglomeration in cell medium, cellular uptake, intracellular localization and Ag release. Despite different agglomeration patterns, there was no evident difference in the uptake or intracellular localization of the citrate and PVP coated AgNPs. However, the 10 nm particles released significantly more Ag compared with all other AgNPs (approx. 24 wt% vs. 4-7 wt%) following 24 h in cell medium. The released fraction in cell medium did not induce any cytotoxicity, thus implying that intracellular Ag release was responsible for the toxicity.ConclusionsThis study shows that small AgNPs (10 nm) are cytotoxic for human lung cells and that the toxicity observed is associated with the rate of intracellular Ag release, a 'Trojan horse' effect.

Project description:Much is anticipated from the development and deployment of nanomaterials in biological organisms, but concerns remain regarding their biocompatibility and target specificity. Here we report our study of the transport, biocompatibility and toxicity of purified and stable silver nanoparticles (Ag NPs, 13.1 ± 2.5 nm in diameter) upon the specific developmental stages of zebrafish embryos using single NP plasmonic spectroscopy. We find that single Ag NPs passively diffuse into five different developmental stages of embryos (cleavage, early-gastrula, early-segmentation, late-segmentation, and hatching stages), showing stage-independent diffusion modes and diffusion coefficients. Notably, the Ag NPs induce distinctive stage and dose-dependent phenotypes and nanotoxicity, upon their acute exposure to the Ag NPs (0-0.7 nM) for only 2 h. The late-segmentation embryos are most sensitive to the NPs with the lowest critical concentration (CNP,c << 0.02 nM) and highest percentages of cardiac abnormalities, followed by early-segmentation embryos (CNP,c < 0.02 nM), suggesting that disruption of cell differentiation by the NPs causes the most toxic effects on embryonic development. The cleavage-stage embryos treated with the NPs develop into a wide variety of phenotypes (abnormal finfold, tail/spinal cord flexure, cardiac malformation/edema, yolk sac edema, and acephaly). These organ structures are not yet developed in cleavage-stage embryos, suggesting that the earliest determinative events to create these structures are ongoing, and disrupted by NPs, which leads to the downstream effects. In contrast, the hatching embryos are most resistant to the Ag NPs, and majority of embryos (94%) develop normally, and none of them develop abnormally. Interestingly, early-gastrula embryos are less sensitive to the NPs than cleavage and segmentation stage embryos, and do not develop abnormally. These important findings suggest that the Ag NPs are not simple poisons, and they can target specific pathways in development, and potentially enable target specific study and therapy for early embryonic development.

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Silver nanoparticles do not alter human osteoclastogenesis but induce cellular uptake.

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Silver nanoparticles do not alter human osteoclastogenesis but induce cellular uptake.

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