Institute of Physiology, University Medical Center of Johannes Gutenberg University Mainz, Duesbergweg 6, 55128, Mainz, Germany.
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128, Mainz, Germany.
Small. 2019 Oct;15(42):e1902992. doi: 10.1002/smll.201902992. Epub 2019 Aug 29.
Nanotheranostics, combining diagnostics and therapy, has the potential to revolutionize treatment of neurological disorders. But one of the major obstacles for treating central nervous system diseases is the blood-brain barrier (BBB) preventing systemic delivery of drugs and optical probes into the brain. To overcome these limitations, nanodiamonds (NDs) are investigated in this study as they are a powerful sensing and imaging platform for various biological applications and possess outstanding stable far-red fluorescence, do not photobleach, and are highly biocompatible. Herein, fluorescent NDs encapsulated by a customized human serum albumin-based biopolymer (polyethylene glycol) coating (dcHSA-PEG) are taken up by target brain cells. In vitro BBB models reveal transcytosis and an additional direct cell-cell transport via tunneling nanotubes. Systemic application of dcHSA-NDs confirms their ability to cross the BBB in a mouse model. Tracking of dcHSA-NDs is possible at the single cell level and reveals their uptake into neurons and astrocytes in vivo. This study shows for the first time systemic NDs brain delivery and suggests transport mechanisms across the BBB and direct cell-cell transport. Fluorescent NDs are envisioned as traceable transporters for in vivo brain imaging, sensing, and drug delivery.
纳米诊断学结合了诊断和治疗，有可能彻底改变神经疾病的治疗方法。但治疗中枢神经系统疾病的主要障碍之一是血脑屏障（BBB）阻止药物和光学探针系统地进入大脑。为了克服这些限制，本研究中研究了纳米金刚石（NDs），因为它们是用于各种生物应用的强大传感和成像平台，并且具有出色的稳定远红荧光，不发生光漂白，并且高度生物相容。在此，通过定制的人血清白蛋白基生物聚合物（聚乙二醇）涂层（dcHSA-PEG）封装的荧光 NDs 被靶脑细胞摄取。体外 BBB 模型揭示了转胞吞作用以及通过隧道纳米管的额外直接细胞间转运。dcHSA-NDs 的系统应用证实了它们在小鼠模型中穿过 BBB 的能力。dcHSA-NDs 的跟踪可以在单细胞水平上进行，并揭示了它们在体内进入神经元和星形胶质细胞的摄取。这项研究首次表明系统的 NDs 脑内递药，并提出了穿过 BBB 和直接细胞间转运的运输机制。荧光 NDs 有望成为体内脑成像、传感和药物递送的可追踪转运体。
