Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic.
Faculty of Biomedical Engineering, Czech Technical University, Nám. Sítná 3105, 272 01 Kladno, Czech Republic.
Biointerphases. 2020 Dec 3;15(6):061009. doi: 10.1116/6.0000525.
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.
荧光纳米金刚石（NDs）表面涂有治疗药物和细胞靶向结构，可作为有效的药物递送工具。然而，在血液中循环的 NDs 最终可能与血脑屏障相互作用，导致不良的病理反应。在这里，我们旨在检测 NDs 与成年脑组织之间的相互作用。首先，我们在体外培养神经元组织并研究细胞活力、再生、细胞因子分泌和纳米金刚石摄取。然后，我们将 NDs 系统地应用于 C57BL/6 动物，并评估纳米金刚石在脑组织中的积累和细胞因子反应。我们发现只有非神经元细胞内化了涂层纳米金刚石，并通过分泌白细胞介素-6 和干扰素-γ做出反应。表达微管蛋白β-III 的神经元来源的细胞没有内化任何 NDs。一旦我们静脉内应用涂层 NDs，我们在成年皮质中没有发现 NDs 的存在，但观察到白细胞介素-1α的短暂释放。我们得出结论，专门的成年神经元细胞不会内化普通或涂层的 NDs。然而，涂层纳米金刚石与皮质组织中存在的非神经元细胞相互作用。此外，涂层纳米金刚石不能穿过血脑屏障，但与相邻的屏障细胞相互作用并引发暂时的细胞因子反应。这项研究代表了关于 NDs 与成年大脑组织相互作用的首次报道。
