Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu, Taiwan.
Nanotechnology. 2014 Mar 28;25(12):125103. doi: 10.1088/0957-4484/25/12/125103. Epub 2014 Feb 27.
Nanoparticles are potential threats to human health and the environment; however, their medical applications as drug carriers targeting cancer cells bring hope to contemporary cancer therapy. As a model drug carrier, gold nanoparticles (GNPs) have been investigated extensively for in vivo toxicity. The effect of GNPs on the immune system, however, has rarely been examined. Antibody-secreting cells were treated with GNPs with diameters ranging from 2 to 50 nm. The GNPs enhanced IgG secretion in a size-dependent manner, with a peak of efficacy at 10 nm. The immune-stimulatory effect reached a maximum at 12 h after treatment but returned to control levels 24 h after treatment. This enhancing effect was validated ex vivo using B-cells isolated from mouse spleen. Evidence from RT-PCR and western blot experiments indicates that GNP-treatment upregulated B-lymphocyte-induced maturation protein 1 (blimp1) and downregulated paired box 5 (pax5). Immunostaining for blimp1 and pax5 in B-cells confirmed that the GNPs stimulated IgG secretion through the blimp1/pax5 pathway. The immunization of mice using peptide-conjugated GNPs indicated that the GNPs were capable of enhancing humoral immunity in a size-dependent manner. This effect was consistent with the bio-distribution of the GNPs in mouse spleen. In conclusion, in vitro, ex vivo, and in vivo evidence supports our hypothesis that GNPs enhance humoral immunity in mouse. The effect on the immune system should be taken into account if nanoparticles are used as carriers for drug delivery. In addition to their toxicity, the immune-stimulatory activity of nanoparticles could play an important role in human health and could have an environmental impact.
纳米粒子对人类健康和环境构成潜在威胁；然而，它们作为靶向癌细胞的药物载体在医学上的应用为当代癌症治疗带来了希望。作为一种模型药物载体，金纳米粒子（GNPs）已被广泛研究其体内毒性。然而，GNPs 对免疫系统的影响却很少被研究。用直径为 2 至 50nm 的 GNPs 处理抗体分泌细胞。GNPs 以尺寸依赖性方式增强 IgG 的分泌，在 10nm 时效果达到峰值。免疫刺激作用在治疗后 12 小时达到最大值，但在治疗后 24 小时恢复到对照水平。这一增强作用在使用从小鼠脾脏分离的 B 细胞进行的离体实验中得到了验证。RT-PCR 和 Western blot 实验的证据表明，GNP 处理上调了 B 淋巴细胞诱导成熟蛋白 1（blimp1）并下调了配对盒 5（pax5）。B 细胞中 blimp1 和 pax5 的免疫染色证实，GNPs 通过 blimp1/pax5 途径刺激 IgG 分泌。用肽偶联的 GNPs 免疫小鼠表明，GNPs 能够以尺寸依赖性方式增强体液免疫。这一效应与 GNPs 在小鼠脾脏中的生物分布一致。总之，体外、离体和体内证据支持我们的假设，即 GNPs 增强了小鼠的体液免疫。如果纳米粒子被用作药物载体，那么它们对免疫系统的影响应该被考虑在内。除了它们的毒性外，纳米粒子的免疫刺激活性可能在人类健康中发挥重要作用，并可能对环境产生影响。
