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

作者：Tomic Sergej; Dokic Jelena; Vasilijic Sasa; Ogrinc Nina; Rudolf Rebeka; Pelicon Primoz; Vucevic Dragana; Milosavljevic Petar; Jankovic Srda; Anzel Ivan; Rajkovic Jelena; Rupnik Marjan Slak; Friedrich Bernd; Colic Miodrag^*

来源：PLos One, 2014, 9(5): e96584.

DOI：10.1371/journal.pone.0096584

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 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, GNP(10) inhibited the necrotic tumor cell-induced maturation and functions of DCs, potentiated their Th2/Th17 polarization capacity, and thus, impaired the DCs%26apos; 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).

• 出版日期2014-5-6
• 单位河北医科大学; 中国人民解放军军事医学科学院