Toxicity of tannic acid-modified silver nanoparticles in keratinocytes: potential for immunomodulatory applications

- Tannic acid-modified AgNPs induced JNK kinase in VK2-E6/E7, while ERK in HaCaT cells.
- Tannic acid-modified AgNPs down-regulated TNF-α and LPS-triggered production of IL-8 in VK2-E6/E7 cells.
- Tannic acid-modified AgNPs applied to scarified mouse ears show no irritant activity.
- Tannic acid-modified AgNPs preserve γδ T cell distribution in the skin after scarification.

Hydrolyzable tannins are known to exhibit anti-inflammatory activity, which can be used in combination with silver nanoparticles (AgNPs) for dermal uses. In this study, we investigated the effects of tannic acid-modified 13, 33, 46 nm and unmodified 10-65 nm AgNPs using the human-derived keratinocyte HaCaT and VK2-E6/E7 cell lines in the form of stationary and spheroids cultures. After exposition to tannic acid-modified AgNPs, VK2-E6/E7 cells showed higher toxicity, increased production of reactive oxygen species (ROS) and activity of JNK stress kinase, while HaCaT cell line demonstrated less ROS production and activation of ERK kinase. AgNPs internalization was detected both in the superficial and internal layers of spheroids prepared from both cell lines. Tannic acid modified AgNPs sized above 30 nm did not induce DNA breaks in comet assay performed in both cell lines. Tannic acid-modified but not unmodified AgNPs down-regulated TNF-α and LPS-triggered production of IL-8 in VK2-E6/E7 but not in HaCaT cells. In summary, tannic acid-modified AgNPs sized above 30 nm show good toxicological profile both in vitro and possess immunomodulatory properties useful for potential dermal applications in humans.