The C3H/HeJ mouse model1 we used in our paper 'Nanoparticles reduce nickel allergy by capturing metal ions'2 is indeed one of many and is not a robust allergy model. Given that nickel-sensitized patients often endure a less heightened response when treated with lower doses of Ni2+ (refs 3, 4), the nickel-sensitized mouse model was used to demonstrate that nanoparticles could indeed reduce Ni2+ exposure. As suggested in the correspondence by Schmidt et al., regardless of the host and cutaneous-response pathways, nanoparticles that sequester nickel on the skin surface may offer protection against all such pathways. Our unpublished control experiments on mice ears showed that Ni2+ did not induce inflammation in non-sensitized healthy mice, which is in agreement with non-sensitized humans that typically do not experience a response to nickel ions5. It is also important to consider that we observed reactions to nickel only after, not during, nickel sensitization. In addition to showing that nanoparticles significantly reduced the inflammatory response induced by Ni2+ in vivo, our in vitro experiments using inductively coupled plasma atomic emission spectrometry confirmed that the nanoparticles did efficiently capture Ni2+ in solution. Furthermore, energy-dispersive X-ray diffraction analysis of intact skin containing artificial sweat showed that the nanoparticles were able to prevent nickel from going through the skin. By performing inductively coupled plasma atomic emission on dissolved skin that had been treated with nickel, we verified that the nanoparticles can reduce the concentration of nickel in the skin from 400 to 2.5 ppm.
In retrospect, a more appropriate title for the paper may have been 'Nanoparticles reduce nickel irritation by capturing metal ions'.
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Vemula, P., Anderson, R. & Karp, J. Animal models for nickel allergy. Nature Nanotech 6, 533 (2011). https://doi.org/10.1038/nnano.2011.144