Analysis of the toxicity of gold nano particles on the immune system: effect on dendritic cell functions (original) (raw)
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Impact of Gold Nanoparticles on the Functions of Macrophages and Dendritic Cells
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Gold nanoparticles (AuNPs) have demonstrated outstanding performance in many biomedical applications. Their safety is recognised; however, their effects on the immune system remain ill defined. Antigen-presenting cells (APCs) are immune cells specialised in sensing external stimulus and in capturing exogenous materials then delivering signals for the immune responses. We used primary macrophages (Ms) and dendritic cells (DCs) of mice as an APC model. Whereas AuNPs did not alter significantly Ms and DCs functions, the exposure to AuNPs affected differently Ms and DCs in their responses to subsequent stimulations. The secretion of inflammatory molecules like cytokines (IL-6, TNF-α), chemokine (MCP-1), and reactive oxygen species (ROS) were altered differently in Ms and DCs. Furthermore, the metabolic activity of Ms was affected with the increase of mitochondrial respiration and glycolysis, while only a minor effect was seen on DCs. Antigen presentation to T cells increased when DCs we...
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Dendritic Cells (DCs) have shown great potential in a variety of immunotherapeutic applications due to their key role in both the innate and adaptive immune response. This study aims to observe the activation and phenotypic changes within the cell population following treatment with a variety of gold nanoparticles (AuNPs). AuNPs are currently being used as drug delivery vehicles, regulators and suppressors of the host immune response. They have easily modified surface chemistry and display high biocompatibility. Developing mechanisms to specifically manipulate DCs utilizing biomaterials will allow for a number of immunotherapeutic approaches to become available to patients suffering from autoimmune diseases such as HIV/AIDS, and cancer. Following treatment with numerous AuNP treatments varying in surface coating and concentration cells should demonstrate no abnormal death or patterns within the cell cycle and should also exhibit elevation in surface markers correlating to tolerizati...
PLoS ONE, 2014
Gold nanoparticles (GNPs) are claimed as outstanding biomedical tools for cancer diagnostics and photo-thermal therapy, but without enough evidence on their potentially adverse immunological effects. Using a model of human dendritic cells (DCs), we showed that 10 nm-and 50 nm-sized GNPs (GNP 10 and GNP 50 , respectively) were internalized predominantly via dynamin-dependent mechanisms, and they both impaired LPS-induced maturation and allostimulatory capacity of DCs, although the effect of GNP 10 was more prominent. However, GNP 10 inhibited LPS-induced production of IL-12p70 by DCs, and potentiated their Th2 polarization capacity, while GNP 50 promoted Th17 polarization. Such effects of GNP 10 correlated with a stronger inhibition of LPS-induced changes in Ca 2+ oscillations, their higher number per DC, and more frequent extraendosomal localization, as judged by live-cell imaging, proton, and electron microscopy, respectively. Even when released from heat-killed necrotic HEp-2 cells, GNP 10 inhibited the necrotic tumor cell-induced maturation and functions of DCs, potentiated their Th2/Th17 polarization capacity, and thus, impaired the DCs' capacity to induce T cell-mediated anti-tumor cytotoxicity in vitro. Therefore, GNP 10 could potentially induce more adverse DC-mediated immunological effects, compared to GNP 50 .
Microscopic analysis of the interaction of gold nanoparticles with cells of the innate immune system
2013
Gold nanoparticles (AuNPs) can interfere with some of the biochemical processes of macrophage cells but the mechanisms of action of these potentially medically-relevant effects are still unclear. Here we study the fate of AuNPs interacting with cells derived from the innate immune system. To visualize AuNPs with nanometer resolution without losing sight of the whole morphology of cells we developed a convenient approach that uses electron and ion microscopy techniques. The inspection using an ion beam to selectively cut where the AuNPs were found, allows for determining their intracellular localizations. We studied the cellular uptake of AuNPs, with or without exposure of the cells to Latrunculin-A, a phagocytosis inhibitor. Results indicate a size dependence of the internalization mechanisms for THP-1 cells. The internalization of larger AuNPs was blocked in the presence of Latrunculin-A, although they could attach to the membrane. Smaller AuNPs though were not blocked by actin depending processes.
Immunological properties of gold nanoparticles
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This review summarizes what is known about the application of gold nanoparticles as an antigen carrier and adjuvant in immunization for the preparation of antibodies in vivo and evaluating their potential for the development of effective vaccines.
Selective inhibitory effects of 50-nm gold nanoparticles on mouse macrophage and spleen cells
Journal of immunotoxicology, 2015
Nanoparticles (NP) are significant to multiple industrial processes, consumer products and medical applications today. The health effects of many different types of NP, however, are largely unknown. The purpose of this study was to test the effects of 50-nm gold NP coated with poly-N-vinylpyrrolidone (PVP) on mouse macrophage and spleen cells with and without lipopolysaccharide (LPS), testing the hypothesis that the NP would modulate immune responses without being overtly toxic. Gold NP had no effect on macrophage viability and, in the absence of LPS, they had no effect on tumor necrosis factor (TNF)-α production as measured by ELISA. The presence of LPS significantly increased the release of TNFα from the macrophages above no-treatment controls, but increasing gold NP concentration led to decreasing release of TNFα. The reactive oxygen species (ROS) produced by exposed macrophages were also reduced compared to untreated controls, both with and without LPS, suggesting some kind of o...
Inorganic nanoparticles as potential regulators of immune response in dendritic cells
Nanomedicine (London, England), 2017
The spontaneous adsorption of proteins on nanoparticles (NPs) in biological media is exploited to prepare complexes of NPs and proteins from cancer cells' lysates for application in cancer immunotherapy. Gold (Au) and silica NPs were synthesized, incubated with cancer cells' lysates and characterized. Dendritic cells (DCs) were challenged with protein-coated NPs, their maturation, viability and morphology were evaluated and lymphocytes T proliferation was determined. Silica and Au NPs bound different pools of biomolecules from lysates, and are therefore promising selective carriers for antigens. When incubated with immature DCs, NPs were efficiently endocytosed without cytotoxicity. Finally, protein-coated AuNPs promoted DC maturation and DC-mediated lymphocyte proliferation, at variance with lysate alone and protein-coated silica NPs, that did not promote DCs maturation. These results demonstrate that the spontaneous formation of protein coronas on NPs represents a possible...
Phagocytosis of Biocompatible Gold Nanoparticles
Langmuir, 2010
We report the evidence for the cellular uptake of gold nanoparticles via the phagocytosis mechanism in murine macrophage cells strongly supported by TEM and optical microscopy. Nanoparticles were prepared using several biocompatible molecules of choice (5-aminovaleric acid, L-DOPA, melatonin, and serotonin hydrochloride) as stabilizers for gold colloids. Their surface chemistry was fully characterized by UV-vis, ATR-FTIR, 1 H NMR, and HR-MAS 1 H NMR spectroscopies, and size distribution was determined by CPS disc centrifuge and TEM. Differences in coatings were evaluated against cellular uptake, and a preferential movement of macrophages toward 5-aminovaleric acid-modified gold nanoparticles was shown, leading to the fast accumulation of nanoparticles in the cytosol.
Gold Nanoparticles Treatment in MCF-7 Spheroid Co-Cultures With Dendritic Cells
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In the last decade biomaterials have increasingly been studied as the next generation of immunotherapeutic treatments for their tendency to induce host response against themselves when implanted. Addressing this significant barrier of host response is a key step in engineering our immune response to target foreign invaders and diseases such as cancer. A promising application of this is gold nanoparticle’s (AuNPs) ability to interact with dendritic cells (DCs) in our bodies. We propose to study this in MCF-7 tumor spheroids and MCF-7 co-culture spheroids to investigate its practical significance.Undergraduat