CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.
School of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, China.
Sci Adv. 2023 Jul 7;9(27):eadg2252. doi: 10.1126/sciadv.adg2252.
The blood circulation is considered the only way for the orally administered nanoparticles to enter the central nervous systems (CNS), whereas non-blood route-mediated nanoparticle translocation between organs is poorly understood. Here, we show that peripheral nerve fibers act as direct conduits for silver nanomaterials (Ag NMs) translocation from the gut to the CNS in both mice and rhesus monkeys. After oral gavage, Ag NMs are significantly enriched in the brain and spinal cord of mice with particle state however do not efficiently enter the blood. Using truncal vagotomy and selective posterior rhizotomy, we unravel that the vagus and spinal nerves mediate the transneuronal translocation of Ag NMs from the gut to the brain and spinal cord, respectively. Single-cell mass cytometry analysis revealed that enterocytes and enteric nerve cells take up significant levels of Ag NMs for subsequent transfer to the connected peripheral nerves. Our findings demonstrate nanoparticle transfer along a previously undocumented gut-CNS axis mediated by peripheral nerves.
血液循环被认为是口服纳米颗粒进入中枢神经系统（CNS）的唯一途径，而器官间非血液途径介导的纳米颗粒转移则知之甚少。在这里，我们表明外周神经纤维在小鼠和恒河猴中充当银纳米材料（Ag NM）从肠道到中枢神经系统转移的直接通道。经口服灌胃后，Ag NM 以颗粒状态显著富集于小鼠的大脑和脊髓中，但不能有效地进入血液。使用干切断术和选择性后根切断术，我们揭示了迷走神经和脊神经分别介导 Ag NM 从肠道到大脑和脊髓的跨神经元转移。单细胞质量细胞术分析显示，肠细胞和肠神经细胞摄取大量的 Ag NM，以便随后转移到相连的外周神经。我们的研究结果表明，纳米颗粒沿着以前未被记录的肠道-中枢神经系统轴通过外周神经进行转移。
