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.
Medical Faculty of the Military Medical Academy, University of Defense, Belgrade, Serbia.
PLoS One. 2014 May 6;9(5):e96584. doi: 10.1371/journal.pone.0096584. eCollection 2014.
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.
金纳米颗粒（GNPs）被认为是癌症诊断和光热治疗的杰出生物医学工具，但它们潜在的免疫不良影响的证据还不够充分。我们使用人树突状细胞（DC）模型表明，10nm 和 50nm 大小的 GNPs（分别为 GNP10 和 GNP50）主要通过网格蛋白依赖的机制被内化，它们都能抑制 LPS 诱导的 DC 成熟和共刺激能力，尽管 GNP10 的作用更为明显。然而，GNP10 抑制 LPS 诱导的 DC 产生 IL-12p70，并增强其 Th2 极化能力，而 GNP50 则促进 Th17 极化。GNP10 的这种作用与 LPS 诱导的 Ca2+振荡变化的抑制更强、每个 DC 中的颗粒数量更多以及通过活细胞成像、质子和电子显微镜分别判断的更频繁的胞外体定位有关。即使从热灭活的坏死 HEp-2 细胞中释放出来，GNP10 也能抑制坏死肿瘤细胞诱导的 DC 成熟和功能，增强其 Th2/Th17 极化能力，从而损害 DC 诱导 T 细胞介导的体外抗肿瘤细胞毒性的能力。因此，与 GNP50 相比，GNP10 可能会引起更不利的 DC 介导的免疫作用。
