1. Immunotoxicity of poly (lactic-co-glycolic acid) nanoparticles: influence of surface properties on dendritic cell activation
- Author
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Saadia Kerdine-Römer, Nicolas Tsapis, Marc Pallardy, Hervé Hillaireau, Simona Mura, Elias Fattal, S Barillet, Institut Galien Paris-Sud (IGPS), and Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
CD4-Positive T-Lymphocytes ,Biocompatibility ,Cell Survival ,Surface Properties ,medicine.medical_treatment ,Biomedical Engineering ,Biocompatible Materials ,02 engineering and technology ,010501 environmental sciences ,Toxicology ,01 natural sciences ,Flow cytometry ,Mice ,chemistry.chemical_compound ,Phagocytosis ,Polylactic Acid-Polyglycolic Acid Copolymer ,medicine ,Animals ,Humans ,Viability assay ,ComputingMilieux_MISCELLANEOUS ,Cell Proliferation ,0105 earth and related environmental sciences ,medicine.diagnostic_test ,technology, industry, and agriculture ,Dendritic Cells ,Dendritic cell ,021001 nanoscience & nanotechnology ,Coculture Techniques ,Cell biology ,Mice, Inbred C57BL ,PLGA ,Cytokine ,chemistry ,[SDV.TOX]Life Sciences [q-bio]/Toxicology ,Cytokines ,Nanoparticles ,Cytokine secretion ,0210 nano-technology ,Intracellular - 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.
- Published
- 2019