Advanced herbal self-assembled nanoplatforms: targeted, stimuli-responsive, and precision therapeutics for human diseases.

Herbal self-assembled nanoplatforms (H-SANs) represent an emerging strategy in herbal nanomedicine by integrating the intrinsic bioactivity of phytochemicals with supramolecular nanoscale organization. Unlike conventional nanocarriers that may be limited by low drug loading, excipient burden, premature release, and scale-up complexity, H-SANs are carrier-free or predominantly bioactive systems formed through noncovalent interactions, including π-π stacking, hydrogen bonding, hydrophobic forces, electrostatic interactions, and metal coordination, among polyphenols, flavonoids, alkaloids, terpenoids, saponins, and related phytochemical components. Reported assemblies can achieve high drug loading, exhibit stimuli-responsive structural changes under disease-associated cues such as acidic pH, redox imbalance, or enzyme overexpression, and can be further engineered with targeting motifs. Preclinical studies have explored their applications in oncology, inflammation, neurodegeneration, metabolic disorders, cardiovascular disease, antimicrobial therapy, wound repair, kidney injury, and bone disorders, where H-SANs may act as bioactive scaffolds as well as delivery systems. However, their translational development remains constrained by dilution-dependent instability, incomplete understanding of in vivo disassembly and parent-drug regeneration, protein corona formation, tumor transport heterogeneity, raw-material variability, manufacturing reproducibility, regulatory classification, and limited human-relevant pharmacokinetic and safety evidence. Emerging strategies, including AI-assisted modeling, rational multicomponent co-assembly, continuous manufacturing, and improved biological validation, may help address these challenges. Overall, H-SANs provide a promising but still largely preclinical framework for high-payload herbal nanomedicine, and their clinical value will require rigorous physicochemical characterization, reproducible manufacturing, and cautious translational validation.