Programmable Self-Assembly of Traditional Chinese Medicine (TCM) Monomers: From Molecular Mechanisms to...

Self-assembled nanosystems based on non-covalent interactions of traditional Chinese medicine (TCM) monomers have attracted extensive attention in drug delivery. In direct carrier-free systems, the active molecules also serve as building units. These systems may reduce the need for extra carriers and provide high drug loading. Hybrid systems may instead depend on polymers, ions, membranes, or other added materials. This review follows a molecular structure-assembly-property-function chain. Molecular features and environmental conditions guide the assembly pathway. The pathway produces structures such as nanoparticles, fibers, ribbons, and hydrogels. These structures have different sizes, shapes, surface properties, stability, mechanical properties, and responses. These properties can then affect drug release, cellular uptake, tissue retention, targeting, and treatment outcomes. Co-assembly adds another level of control. Component identity and component ratio can change molecular interactions, morphology, and function. The review separates control shown under tested conditions from full programmable design. Most reported systems are controllable only under tested conditions. Few studies have reached full programmable design. This review summarizes molecular rules, control factors, co-assembly modes, and characterization methods. It also discusses applications in druggability, disease treatment, targeted delivery, tissue repair, and theranostics. The review compares direct monomer assembly with polymer-, ion-, membrane-, and carrier-assisted systems. It also discusses reproducibility, biological stability, safety, scale-up, and regulation. The review aims to support more reproducible and predictable design of TCM-derived nanomedicines.