title: Size-dependent effects of gold nanoparticles uptake on maturation and antitumor functions of human dendritic cells in vitro.
abstract: 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 (GNP10 and GNP50, respectively) were internalized predominantly via dynamin-dependent mechanisms, and they both impaired LPS-induced maturation and allostimulatory capacity of DCs, although the effect of GNP10 was more prominent. However, GNP10 inhibited LPS-induced production of IL-12p70 by DCs, and potentiated their Th2 polarization capacity, while GNP50 promoted Th17 polarization. Such effects of GNP10 correlated with a stronger inhibition of LPS-induced changes in Ca2+ oscillations, their higher number per DC, and more frequent extra-endosomal localization, as judged by live-cell imaging, proton, and electron microscopy, respectively. Even when released from heat-killed necrotic HEp-2 cells, GNP10 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, GNP10 could potentially induce more adverse DC-mediated immunological effects, compared to GNP50.
authors.affiliation: Medical Faculty of the Military Medical Academy, University of Defense, Belgrade, Serbia; Institute for Medical Research of the Military Medical Academy, University of Defense, Belgrade, Serbia.
authors.forename: Sergej
authors.initials: S
authors.lastname: Tomić
authors.affiliation: Medical Faculty of the Military Medical Academy, University of Defense, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Ðokić
authors.affiliation: Medical Faculty of the Military Medical Academy, University of Defense, Belgrade, Serbia; Institute for Medical Research of the Military Medical Academy, University of Defense, Belgrade, Serbia.
authors.forename: Saša
authors.initials: S
authors.lastname: Vasilijić
authors.affiliation: Microanalytical Center, Jožef Stefan Institute, Ljubljana, Slovenia; LOTRIČ Metrology, Selca, Slovenia.
authors.forename: Nina
authors.initials: N
authors.lastname: Ogrinc
authors.affiliation: Faculty of Mechanical Engineering, University of Maribor, Maribor, Slovenia; Zlatarna Celje d.d., Celje, Slovenia.
authors.forename: Rebeka
authors.initials: R
authors.lastname: Rudolf
authors.affiliation: Microanalytical Center, Jožef Stefan Institute, Ljubljana, Slovenia.
authors.forename: Primož
authors.initials: P
authors.lastname: Pelicon
authors.affiliation: Medical Faculty of the Military Medical Academy, University of Defense, Belgrade, Serbia; Institute for Medical Research of the Military Medical Academy, University of Defense, Belgrade, Serbia.
authors.forename: Dragana
authors.initials: D
authors.lastname: Vučević
authors.affiliation: Institute for Medical Research of the Military Medical Academy, University of Defense, Belgrade, Serbia.
authors.forename: Petar
authors.initials: P
authors.lastname: Milosavljević
authors.affiliation: University Children's Hospital, Belgrade, Serbia.
authors.forename: Srđa
authors.initials: S
authors.lastname: Janković
authors.affiliation: Faculty of Mechanical Engineering, University of Maribor, Maribor, Slovenia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Anžel
authors.affiliation: Medical Faculty, University of Niš, Niš, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Rajković
authors.affiliation: Medical Faculty, University of Maribor, Maribor, Slovenia.
authors.forename: Marjan Slak
authors.initials: MS
authors.lastname: Rupnik
authors.affiliation: Department of Process Metallurgy and Metal Recycling, Rheinisch-Westfälische Technische Hochschule, Aachen University, Aachen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Friedrich
authors.affiliation: Medical Faculty of the Military Medical Academy, University of Defense, Belgrade, Serbia; Medical Faculty, University of Niš, Niš, Serbia.
authors.forename: Miodrag
authors.initials: M
authors.lastname: Colić
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology*; D020013:Calcium Signaling / Q000187:drug effects / Q000276:immunology; D016764:Cell Polarity / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006046:Gold / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D053758:Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D008070:Lipopolysaccharides; D018664:Interleukin-12; D006046:Gold