Application of Plant-Derived Nanovesicles in Brain Diseases: A Component-Structure Theory Perspective
Brain disease treatment is constrained by the blood-brain barrier (BBB), resulting in insufficient drug accumulation in the brain, nonspecific distribution, and immune clearance. Although synthetic nanocarriers improve pharmacokinetics, their long-term stability and biosafety remain uncertain. Plant-derived nanovesicles (PDNVs) have emerged as therapeutic and delivery platforms owing to natural lipid bilayers, biocompatibility, low immunogenicity, and scalability. PDNVs carry lipids, proteins, nucleic acids, and bioactive small molecules, integrating delivery capability with intrinsic therapeutic activity. Component-structure theory interprets multicomponent systems through elemental structure, quantitative-ratio structure, and phase structure. From this perspective, PDNVs are natural composite nanovesicles formed by ordered integration of endogenous components within membrane-confined spaces. This review examines relationships among PDNVs composition, membrane architecture, BBB-crossing delivery, and therapeutic effects in brain diseases, and summarizes engineering strategies for functional optimization. It provides an analytical framework for rational design, quality control, and optimization of PDNVs as central nervous system drug delivery platforms. The review cites experimental evidence including grapefruit-derived nanovesicles for intestinal macrophage targeting, ginger-derived exosomes for glioblastoma, ginseng-derived exosome-like nanoparticles for active BBB penetration, and Momordica charantia small extracellular vesicles mitigating neuronal ferroptosis via GPX4 ubiquitination inhibition in ischemic stroke. These studies demonstrate PDNVs' dual role in preserving endothelial integrity while modulating the tumor microenvironment, and their capacity for nose-to-brain delivery in Parkinson's disease models. The component-structure framework enables systematic engineering of PDNVs for enhanced BBB penetration and therapeutic efficacy.