Size-Dependent Effects of Gold Nanoparticles Uptake on Maturation and Antitumor Functions of Human Dendritic Cells In Vitro

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 extra-endosomal 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).