Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA, 90095, USA.
College of Life Science and Technology, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China.
Adv Mater. 2019 May;31(18):e1807557. doi: 10.1002/adma.201807557. Epub 2019 Feb 25.
Central nervous system (CNS) diseases are the leading cause of morbidity and mortality; their treatment, however, remains constrained by the blood-brain barrier (BBB) that impedes the access of most therapeutics to the brain. A CNS delivery platform for protein therapeutics, which is achieved by encapsulating the proteins within nanocapsules that contain choline and acetylcholine analogues, is reported herein. Mediated by nicotinic acetylcholine receptors and choline transporters, such nanocapsules can effectively penetrate the BBB and deliver the therapeutics to the CNS, as demonstrated in mice and non-human primates. This universal platform, in general, enables the delivery of any protein therapeutics of interest to the brain, opening a new avenue for the treatment of CNS diseases.
中枢神经系统（CNS）疾病是发病率和死亡率的主要原因；然而，由于血脑屏障（BBB）的存在，大多数治疗药物都无法进入大脑，其治疗仍然受到限制。本文报道了一种用于蛋白质治疗药物的中枢神经系统递药平台，该平台通过将蛋白质封装在含有胆碱和乙酰胆碱类似物的纳米胶囊中来实现。通过烟碱型乙酰胆碱受体和胆碱转运体的介导，这些纳米胶囊可以有效地穿透血脑屏障并将治疗药物递送到中枢神经系统，这在小鼠和非人类灵长类动物中得到了验证。总的来说，这个通用平台使任何有兴趣的蛋白质治疗药物都能够递送到大脑，为治疗中枢神经系统疾病开辟了新途径。
