Department of Pharmacology and Chemical Biology, Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education & Shanghai, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
ACS Nano. 2024 Aug 27;18(34):22752-22779. doi: 10.1021/acsnano.4c06851. Epub 2024 Aug 12.
Recent years have witnessed rapid progress in the discovery of therapeutic proteins and peptides for the treatment of central nervous system (CNS) diseases. However, their clinical applications have been considerably hindered by challenges such as low biomembrane permeability, poor stability, short circulation time, and the formidable blood-brain barrier (BBB). Recently, substantial improvements have been made in understanding the dynamics of the BBB and developing efficient approaches for delivering proteins and peptides to the CNS, especially by using various nanoparticles. Herein, we present an overview of the up-to-date understanding of the BBB under physiological and pathological conditions, emphasizing their effects on brain drug delivery. We summarize advanced strategies and elucidate the underlying mechanisms for delivering proteins and peptides to the brain. We highlight the developments and applications of nanocarriers in treating CNS diseases via BBB crossing. We also provide critical opinions on the limitations and obstacles of the current strategies and put forward prospects for future research.
近年来，治疗中枢神经系统（CNS）疾病的治疗性蛋白和肽的发现取得了快速进展。然而，由于生物膜通透性低、稳定性差、循环时间短和血脑屏障（BBB）的强大等挑战，它们的临床应用受到了相当大的阻碍。最近，人们对 BBB 的动力学及其向 CNS 输送蛋白质和肽的有效方法有了更深入的了解，特别是通过使用各种纳米粒子。本文综述了生理和病理条件下 BBB 的最新研究进展，强调了它们对脑内药物输送的影响。我们总结了将蛋白质和肽递送到大脑的先进策略，并阐明了其潜在机制。我们重点介绍了通过 BBB 穿越治疗 CNS 疾病的纳米载体的发展和应用。我们还对当前策略的局限性和障碍提出了批评，并对未来的研究提出了展望。
