Li Yuanke, Liu Ruiying, Zhao Zhen
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences and Frontiers Science Center for Cell Responses, Nankai University, Tianjin 300071, China.
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin 300457, China.
Pharmaceutics. 2025 Jan 15;17(1):109. doi: 10.3390/pharmaceutics17010109.
Brain diseases pose significant treatment challenges due to the restrictive nature of the blood-brain barrier (BBB). Recent advances in targeting macromolecules offer promising avenues for overcoming these obstacles through receptor-mediated transcytosis (RMT). We summarize the current progress in targeting brain drug delivery with macromolecules for brain diseases. This exploration details the transport mechanisms across the BBB, focusing on RMT and its use of natural ligands for drug delivery. Furthermore, the review examines macromolecular ligands such as antibodies, peptides, and aptamers that leverage RMT for effective BBB traversal. Advancements in macromolecules-based delivery systems for brain diseases are summarized, emphasizing their therapeutic potential and limitations. Finally, emerging RMT strategies, including viral vectors, exosomes, and boron neutron capture therapy, are discussed for their precision in brain-targeted treatments. This comprehensive overview underscores the potential of RMT-based approaches to revolutionize brain disease therapy.
由于血脑屏障（BBB）的限制性，脑部疾病带来了重大的治疗挑战。靶向大分子的最新进展为通过受体介导的转胞吞作用（RMT）克服这些障碍提供了有前景的途径。我们总结了目前利用大分子进行脑部疾病靶向药物递送的进展。本探索详细介绍了穿过血脑屏障的转运机制，重点是RMT及其利用天然配体进行药物递送的情况。此外，该综述还研究了利用RMT实现有效穿越血脑屏障的大分子配体，如抗体、肽和适体。总结了用于脑部疾病的基于大分子的递送系统的进展，强调了它们的治疗潜力和局限性。最后，讨论了新兴的RMT策略，包括病毒载体、外泌体和硼中子俘获疗法在脑部靶向治疗中的精准性。这一全面概述强调了基于RMT的方法彻底改变脑部疾病治疗的潜力。
