Abstract
BackgroundAlthough the surface area metric has been proposed as a possible dose-metric for nanoparticles (NPs), it is limited to low-solubility NPs and the dose-metric for high-solubility NPs is poorly understood. In this study, we aimed to assess the appropriate dose-metric or response-metric for NPs using two cobalt (Co)-based NPs, cobalt monoxide (CoO) and cobalt oxide (Co3O4), which both show distinctive solubility, and determine the role of their soluble Co ions in inflammation.MethodsWe evaluated the physicochemical properties of NPs, including solubility in artificial lysosomal fluid (ALF, pH 5.5). Acute lung inflammogenicity was evaluated by bronchoalveolar lavage fluid analysis using the rat intratracheal instillation model. The appropriate response-metric was then determined by plotting several dose-metrics against parameters for lung inflammation. To investigate the effect of the soluble fraction of CoO NPs, the equivalent doses of Co ions from CoCl2 were instilled.ResultsThe Co3O4 and CoO NPs showed about 11.46 % and 92.65 % solubility in ALF, respectively. Instillation of Co3O4 NPs produced neutrophilic inflammation, but CoO NPs induced eosinophilic inflammation. The number of eosinophils showed good correlation with the soluble Co ions dose from NPs (r2 = 0.987, p <0.001), while the number of neutrophils showed good correlation with the surface area dose of the biopersistent NPs (r2 = 0.876, p <0.001). Instillation of CoCl2 showed a similar type and magnitude of inflammation as CoO NPs.ConclusionsIn the Co-based NPs, the eosinophilic inflammation was produced by Co ions based on the ion metric, while the neutrophilic inflammation was developed based on the surface area metric of the biopersistent NPs.
Highlights
The surface area metric has been proposed as a possible dose-metric for nanoparticles (NPs), it is limited to low-solubility NPs and the dose-metric for high-solubility NPs is poorly understood
The average size of Co3O4 and cobalt monoxide (CoO) NPs measured by transmission electron microscopy (TEM) were 20.2 and 65.4 nm, respectively
Co3O4 NPs were less agglomerated than CoO NPs when dispersed in distilled water (DW), while both NPs showed similar size range about 450 nm when dispersed in phosphate-buffered saline (PBS) (Table 1)
Summary
The surface area metric has been proposed as a possible dose-metric for nanoparticles (NPs), it is limited to low-solubility NPs and the dose-metric for high-solubility NPs is poorly understood. We aimed to assess the appropriate dose-metric or response-metric for NPs using two cobalt (Co)-based NPs, cobalt monoxide (CoO) and cobalt oxide (Co3O4), which both show distinctive solubility, and determine the role of their soluble Co ions in inflammation. In an intratracheal instillation model, the SA metric for low-solubility NPs has been proposed as a better metric than either mass or number [5,6,7]. Under a SA metric, the number of neutrophils of low-solubility low-toxicity NPs showed an overlapped dose–response curve, while intrinsic factors such as surface reactivity contribute to the slope of the curves for low-solubility high-toxicity NPs [5, 7]
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