Research progress of blood-brain barrier penetrating and brain diseases therapy by natural biopolymer - based nanomedicine delivery systems.

Brain diseases are one of the most critical threats to human health. The blood-brain barrier (BBB) prevents drugs from entering the brain, rendering standard treatments for neurological illnesses ineffective. In recent years, there has been an increase in interest in nanotechnology-based research to develop innovative drug delivery systems (NDDS) for drug loading, BBB penetration, and precision delivery to diseased areas. Nanocarriers made from natural biomaterials, in particular, solve the drawbacks of standard nanocarriers, such as low stability and inadequate targeting, while simultaneously providing benefits such as simplicity of modification and good biodegradability. This review focuses on the most recent advances in NDDS based on natural biomaterials for overcoming the BBB in treating brain diseases, with a particular emphasis on the methods and mechanisms by which natural biopolymers-such as polysaccharides, peptides, and polynucleotides-break through the BBB and enhance brain-targeted delivery. We explore current challenges and future application prospects of natural biopolymers in permeable nanomedicine delivery systems for the BBB, aiming to provide key insights for advancing cross-BBB delivery platforms toward smarter, multifunctional development, subsequent research, and translational applications.