Evaluation of the skin-sensitizing potential of gold nanoparticles and the impact of established dermal sensitivity on the pulmonary immune response to various forms of gold

Gold nanoparticles (AuNP) are largely biocompatible; however, many studies have demonstrated their potential to modulate various immune cell functions. The potential allergenicity of AuNP remains unclear despite the recognition of gold as a common contact allergen. In these studies, AuNP (29 nm) dermal sensitization potential was assessed via Local Lymph Node Assay (LLNA). Soluble gold (III) chloride (AuCl3) caused lymph node (LN) expansion (SI 10.9), whereas bulk particles (Au, 942 nm) and AuNP did not. Next, the pulmonary immune effects of AuNP (10, 30, 90 µg) were assessed 1, 4, and 8 days post-aspiration. All markers of lung injury and inflammation remained unaltered, but a dose-responsive increase in LN size was observed. Finally, mice were dermally-sensitized to AuCl3 then aspirated once, twice, or three times with Au or AuNP in doses normalized for mass or surface area (SA) to assess the impact of existing contact sensitivity to gold on lung immune responses. Sensitized animals exhibited enhanced responsivity to the metal, wherein subsequent immune alterations were largely conserved with respect to dose SA. The greatest increase in bronchoalveolar lavage (BAL) lymphocyte number was observed in the high dose group – simultaneous to preferential expansion of BAL/LN CD8+ T-cells. Comparatively, the lower SA-based doses of Au/AuNP caused more modest elevations in BAL lymphocyte influx (predominantly CD4+ phenotype), exposure-dependent increases in serum IgE, and selective expansion/activation of LN CD4+ T-cells and B-cells. Overall, these findings suggest that AuNP are unlikely to cause sensitization; however, established contact sensitivity to gold may increase immune responsivity following pulmonary AuNP exposure.

金纳米颗粒（Gold nanoparticles, AuNP）具备优异的生物相容性，但多项研究已证实其可调节多种免疫细胞的功能。尽管金本身属于常见的接触性变应原，金纳米颗粒的潜在致敏性仍未明确。本研究中，研究者通过局部淋巴结试验（Local Lymph Node Assay, LLNA）评估了粒径29 nm的金纳米颗粒的皮肤致敏潜能：可溶性氯化金(III)（AuCl₃）可引发淋巴结扩增（刺激指数SI=10.9），而本体金颗粒（粒径942 nm）与金纳米颗粒均未出现该效应。随后，研究者分别在吸入染毒后1、4、8天，评估了10、30、90 μg剂量金纳米颗粒的肺部免疫效应。结果显示，肺损伤与炎症的各项标志物均未发生显著改变，但淋巴结体积呈现剂量依赖性增大。最后，研究者先对小鼠进行氯化金(III)皮肤致敏，随后以按质量或表面积（Surface Area, SA）归一化剂量的本体金或金纳米颗粒，对其开展1次、2次或3次吸入染毒，以评估已建立的金接触致敏状态对肺部免疫应答的影响。致敏小鼠对该金属的反应性显著增强，后续的免疫改变在很大程度上与表面积剂量呈现相关性。在高剂量组中，支气管肺泡灌洗（Bronchoalveolar Lavage, BAL）淋巴细胞数量增幅最为显著，同时伴随BAL/淋巴结内CD8+T细胞的优先扩增。与之相比，基于表面积的低剂量本体金/金纳米颗粒染毒仅引起支气管肺泡灌洗液淋巴细胞浸润轻度升高（以CD4+表型为主），并出现暴露依赖性的血清免疫球蛋白E（IgE）水平升高，以及淋巴结内CD4+T细胞与B细胞的选择性扩增与活化。总体而言，本研究结果提示金纳米颗粒几乎不会引发致敏反应，但已建立的金接触致敏状态可能会增强肺部暴露于金纳米颗粒后的免疫应答强度。