Center for Creative Convergence Education, Hanyang University, Seoul, 04763, Republic of Korea.
Institute of Next Generation Material Design, Hanyang University, Seoul, 04763, Republic of Korea.
J Nanobiotechnology. 2024 Mar 17;22(1):118. doi: 10.1186/s12951-024-02364-0.
The assessment of AgNPs toxicity in vitro and in vivo models are frequently conflicting and inaccurate. Nevertheless, single cell immunological responses in a heterogenous environment have received little attention. Therefore, in this study, we have performed in-depth analysis which clearly revealed cellular-metal ion association as well as specific immunological response. Our study didn't show significant population differences in PMBC between control and AgNPs group implying no toxicological response. To confirm it further, deep profiling identified differences in subsets and differentially expressed genes (DEGs) of monocytes, B cells and T cells. Notably, monocyte subsets showed significant upregulation of metallothionein (MT) gene expression such as MT1G, MT1X, MT1E, MT1A, and MT1F. On the other hand, downregulation of pro-inflammatory genes such as IL1β and CCL3 in both CD16 + and CD16- monocyte subsets were observed. This result indicated that AgNPs association with monocyte subsets de-promoted inflammatory responsive genes suggesting no significant toxicity observed in AgNPs treated group. Other cell types such as B cells and T cells also showed negligible differences in their subsets suggesting no toxicity response. Further, AgNPs treated group showed upregulation of cell proliferation, ribosomal synthesis, downregulation of cytokine release, and T cell differentiation inhibition. Overall, our results conclude that treatment of AgNPs to PMBC cells didn't display immunological related cytotoxicity response and thus motivate researchers to use them actively for biomedical applications.
体外和体内模型评估 AgNPs 的毒性经常存在冲突和不准确。然而，异质环境中的单细胞免疫反应却很少受到关注。因此，在这项研究中，我们进行了深入的分析，清楚地揭示了细胞-金属离子的关联以及特定的免疫反应。我们的研究没有显示控制组和 AgNPs 组之间 PMBC 中群体差异有统计学意义，这意味着没有毒理学反应。为了进一步证实这一点，深度分析确定了单核细胞、B 细胞和 T 细胞亚群和差异表达基因（DEGs）的差异。值得注意的是，单核细胞亚群中金属硫蛋白（MT）基因表达明显上调，如 MT1G、MT1X、MT1E、MT1A 和 MT1F。另一方面，在 CD16+和 CD16-单核细胞亚群中观察到促炎基因如 IL1β 和 CCL3 的下调。这一结果表明，AgNPs 与单核细胞亚群的结合抑制了促炎反应基因的表达，表明在 AgNPs 处理组中没有观察到明显的毒性。其他细胞类型，如 B 细胞和 T 细胞，其亚群也显示出可忽略不计的差异，表明没有毒性反应。此外，AgNPs 处理组表现出细胞增殖、核糖体合成的上调，细胞因子释放的下调，以及 T 细胞分化抑制。总的来说，我们的结果表明，AgNPs 处理 PMBC 细胞没有显示出与免疫相关的细胞毒性反应，因此促使研究人员积极将其用于生物医学应用。
