Colloidal silver products are sold for a wide range of disinfectant and health applications. This has increased the potential for human exposure to silver nanoparticles (AgNPs) and ions (Ag⁺), for which oral ingestion is considered to be a major route of exposure. Our objective was to evaluate and compare the toxicity of two commercially available colloidal silver products on two human intestinal epithelial models under realistic exposure conditions.

Mesosilver™ and AgC were characterized and a concentration range between 0.1 and 12 μg/mL chosen. Caco-2 cells vs co-culture of Caco-2 and mucus-secreting HT29-MTX cells (90/10) were used. Repeated exposure was carried out to determine cell viability over 18 days of cell differentiation in 24-well plates. Selected concentrations (0.1, 1, and 3 μg/mL) were tested on cells cultured in E-plates and Transwells with the same repeated exposure regimen, to determine cell impedance, and cell viability and trans-epithelial electrical resistance (TEER), respectively. Silver uptake, intracellular localisation, and translocation were determined by CytoViva™, HIM-SIMS, and ICP-MS. Genotoxicity was determined on acutely-exposed proliferating Caco-2 cells by γH2AX immunofluorescence staining.

Repeated exposure of a given concentration of AgC, which is composed solely of ionic silver, generally exerted more toxic effects on Caco-2 cells than Mesosilver™, which contains a mix of AgNPs and ionic silver. Due to its patchy structure, the presence of mucus in the Caco-2/HT29-MTX co-culture only slightly mitigated the deleterious effects on cell viability. Increased genotoxicity was observed for AgC on proliferating Caco-2 cells. Silver uptake, intracellular localisation, and translocation were similar.

In conclusion, Mesosilver™ and AgC colloidal silver products show different levels of gut toxicity due to the forms of distinct silver (AgNPs and/or Ag⁺) contained within. This study highlights the applicability of high-resolution (chemical) imaging to detect and localize silver and provides insights into its uptake mechanisms, intracellular fate and cellular effects.

胶态银产品可用于各种消毒和健康应用。这增加了人类暴露于银纳米颗粒（AgNPs）和离子（Ag ⁺）的可能性，而银纳米颗粒和离子被认为是口服摄入的主要途径。我们的目的是评估和比较两种商业上可买到的胶体银产品在实际暴露条件下对两种人肠上皮模型的毒性。

对Mesosilver™和AgC进行了表征，并选择了0.1至12μg/ mL的浓度范围。使用Caco-2细胞与Caco-2和分泌粘液的HT29-MTX细胞（90/10）的共培养。重复暴露以测定在24孔板中分化18天后的细胞活力。在相同的重复暴露方案下，在E板和Transwells中培养的细胞上测试所选浓度（0.1、1和3μg/ mL），分别测定细胞阻抗，细胞活力和跨上皮电阻（TEER） 。通过CytoViva™，HIM-SIMS和ICP-MS确定银的吸收，细胞内定位和易位。通过γH2AX免疫荧光染色对急性暴露的增殖Caco-2细胞进行基因毒性测定。

重复暴露给定浓度的仅由离子银组成的AgC，通常比含有AgNP和离子银的Mesosilver™对Caco-2细胞产生更大的毒性作用。由于其斑驳的结构，Caco-2 / HT29-MTX共培养物中粘液的存在仅略微减轻了对细胞生存力的有害影响。观察到AgC对增殖的Caco-2细胞的遗传毒性增加。银摄取，细胞内定位和易位相似。

总之，由于其中包含的不同银（AgNP和/或Ag ⁺）形式，Mesosilver™和AgC胶态银产品显示出不同程度的肠道毒性。这项研究强调了高分辨率（化学）成像技术对银的检测和定位的适用性，并提供了对其吸收机制，细胞内命运和细胞效应的见解。