Coated nanodiamonds interact with tubulin beta-III negative cells of adult brain tissue

Fluorescent nanodiamonds (NDs) coated with therapeutics and cell-targeting structures serve as effective tools for drug delivery. However, NDs circulating in blood can eventually interact with the blood-brain barrier, resulting in undesired pathology. Here, we aimed to detect interaction between NDs and adult brain tissue. First, we cultured neuronal tissue with ND ex vivo and studied cell prosperity, regeneration, cytokine secretion, and nanodiamond uptake. Then, we applied NDs systemically into C57BL/6 animals and assessed accumulation of nanodiamonds in brain tissue and cytokine response. We found that only non-neuronal cells internalized coated nanodiamonds and responded by excretion of interleukin-6 and interferon-γ. Cells of neuronal origin expressing tubulin beta-III did not internalize any NDs. Once we applied coated NDs intravenously, we found no presence of NDs in the adult cortex but observed transient release of interleukin-1α. We conclude that specialized adult neuronal cells do not internalize plain or coated NDs. However, coated nanodiamonds interact with non-neuronal cells present within the cortex tissue. Moreover, the coated NDs do not cross the blood-brain barrier but they interact with adjacent barrier cells and trigger a temporary cytokine response. This study represents the first report concerning interaction of NDs with adult brain tissue.