Amino Acid Directed Helical Assemblies of Natural Berberine for Chirality-Dependent Photodynamic Antibacterial...

While the biological effects of chiral pharmaceuticals at molecular level have been extensively studied, research remains limited on how chiral materials derived from natural herbal components exert biomedical effects at higher hierarchical levels. Herein, it is reported that helical nanostructures co-assembled from a traditional Chinese medicine-derived berberine (BBR) and an amino acid derivative (Fmoc-Y) exhibit supramolecular-chirality-dependent photodynamic antibacterial activity. The inherent molecular chirality of the Fmoc-Y component directs the organization of achiral BBR into chiral nanofibers. The experimental results reveal that supramolecular chirality governs nanofiber adsorption on bacterial surfaces and subsequent membrane penetration. Compared with left-handed nanofibers, the chirality-matched right-handed ones enable more efficient intracellular delivery of BBR and reactive oxygen species (ROS) generation, leading to superior bacterial inhibition. This work highlights, for the first time, the unique role of supramolecular chirality in biomedicine applications based on natural herbal components, demonstrating how supramolecular chiral engineering synergizes with natural pharmacophores to develop high-efficiency antimicrobial systems and advanced theranostic platforms.