Jiangsu Key Laboratory of Molecular Imaging and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009, China; Innovation Center of NanoMedicine, Kawasaki Institute of Industrial Promotion, 3-25-14, Tonomachi, Kawasaki-ku, Kawasaki, 210-0821, Japan.
Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, 20892, USA.
Biomaterials. 2019 Dec;224:119491. doi: 10.1016/j.biomaterials.2019.119491. Epub 2019 Sep 14.
Increasing attention has been paid to the diseases of central nervous system (CNS). The penetration efficiency of most CNS drugs into the brain parenchyma is rather limited due to the existence of blood-brain barrier (BBB). Thus, BBB crossing for drug delivery to CNS remains a significant challenge in the development of neurological therapeutics. Because of the advantageous properties (e.g., relatively high drug loading content, controllable drug release, excellent passive and active targeting, good stability, biodegradability, biocompatibility, and low toxicity), nanomaterials with BBB-crossability have been widely developed for the treatment of CNS diseases. This review summarizes the current understanding of the physiological structure of BBB, and provides various nanomaterial-based BBB-crossing strategies for brain delivery of theranostic agents, including intranasal delivery, temporary disruption of BBB, local delivery, cell penetrating peptide (CPP) mediated BBB-crossing, receptor mediated BBB-crossing, shuttle peptide mediated BBB-crossing, and cells mediated BBB-crossing. Clinicians, biologists, material scientists and chemists are expected to be interested in this review.
人们越来越关注中枢神经系统(CNS)疾病。由于存在血脑屏障(BBB),大多数 CNS 药物进入脑实质的穿透效率相当有限。因此,对于 CNS 递药来说,BBB 穿越仍然是神经治疗学发展中的一个重大挑战。由于具有有利的性质(例如,相对较高的药物装载含量、可控的药物释放、出色的被动和主动靶向、良好的稳定性、生物降解性、生物相容性和低毒性),具有 BBB 穿越能力的纳米材料已被广泛开发用于治疗 CNS 疾病。本文综述了对 BBB 生理结构的现有认识,并提供了各种基于纳米材料的 BBB 穿越策略,用于治疗剂的脑内递药,包括鼻内递药、BBB 暂时破坏、局部递药、细胞穿透肽(CPP)介导的 BBB 穿越、受体介导的 BBB 穿越、穿梭肽介导的 BBB 穿越和细胞介导的 BBB 穿越。临床医生、生物学家、材料科学家和化学家有望对这篇综述感兴趣。