ABSTRACT
Modified nanoparticles (NPs) can interact with the immune system by causing its activation to fight tumors or for vaccination. During this activation, dendritic cells (DCs) are effective in generating robust immune response. However, the effect of nanomaterials on dendritic cell (DC) maturation, and the associated adjuvant effect, should be assessed as a novel biocompatibility criteria for biomaterials since immune consequences may constitute potential complications in nanomedicine. Among emerging biomaterials, poly(lactic-co-glycolic acid) NPs (PLGA NPs) are widely explored for various applications in which the degree of desired adjuvant effect may vary. As contradictory results are reported regarding their effects on DCs, we aimed at clarifying this point with particular emphasis on the relative impact of particle surface properties. To that end, NP uptake and effects on the viability, phenotype, and secretory activity of DC primary cultures. Intracellular signaling pathways were explored and evaluated. Immature human and murine DCs were exposed to cationic, neutral, or anionic PLGA NPs. Particle uptake was assessed by both confocal microscopy and flow cytometry. Cell viability was then evaluated prior to the study of maturation by examination of both surface marker expression and cytokine release. Our results demonstrate that PLGA NPs are rapidly engulfed by DCs and do not exert cytotoxic effects. However, upon exposure to PLGA NPs, DCs showed phenotypes and cytokine secretion profiles consistent with maturation which resulted, at least in part, from the transient intracellular activation of mitogen-activated protein kinases (MAPKs). Interestingly, NP-specific stimulation patterns were observed since NP surface properties had a sensible influence on the various parameters measured.
Subject(s)
Biocompatible Materials/toxicity , Dendritic Cells/drug effects , Nanoparticles/toxicity , Phagocytosis/drug effects , Polylactic Acid-Polyglycolic Acid Copolymer/toxicity , Animals , Biocompatible Materials/chemistry , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , Cell Proliferation/drug effects , Cell Survival/drug effects , Cell Survival/immunology , Coculture Techniques , Cytokines/metabolism , Dendritic Cells/immunology , Humans , Mice , Mice, Inbred C57BL , Nanoparticles/chemistry , Phagocytosis/immunology , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/immunology , Surface PropertiesABSTRACT
Titania nanoparticles are produced by tons, and included in commercial products, raising concerns about their potential impact on human health. This study relates their cytotoxic and genotoxic impact on a cell line representative of human lung, namely A549 alveolar epithelial cells.
Subject(s)
Lung Neoplasms/physiopathology , Metal Nanoparticles/toxicity , Mutagenicity Tests/methods , Toxicity Tests, Acute/methods , Cell Line, Tumor , Cell Survival/drug effects , Cytotoxins/toxicity , Dose-Response Relationship, Drug , Humans , Mutagens/toxicity , Titanium/toxicityABSTRACT
Silicon carbide (SiC) is considered a highly biocompatible material, consequently SiC nanoparticles (NPs) have been proposed for potential applications in diverse areas of technology. Since no toxicological data are available for these NPs, the aim of this study was to draw their global toxicological profile on A549 lung epithelial cells, using a battery of classical in vitro assays. Five SiC-NPs, with varying diameters and Si/C ratios were used, and we show that these SiC-NPs are internalized in cells where they cause a significant, though limited, cytotoxic effect. Cell redox status is deeply disturbed: SiC-NP exposure cause reactive oxygen species production, glutathione depletion and inactivation of some antioxidant enzymes: glutathione reductase, superoxide dismutase, but not catalase. Finally, the alkaline comet assay shows that SiC-NPs are genotoxic. Taken together, these data prove that SiC-NPs biocompatibility should be revisited.
