Advanced Noninvasive Strategies for the Brain Delivery of Therapeutic Proteins and Peptides

作者：Jiayuan Lin, Zhihua Yu, Xiaoling Gao · 发表于：ACS Nano · 年份：2024 · DOI：10.1021/acsnano.4c06851 · 被引用次数：23 · 研究领域：RNA Interference and Gene Delivery、Nerve injury and regeneration、Lipid Membrane Structure and Behavior

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.