Carrier-free self-assembled nanoparticles derived from traditional Chinese medicine active components: construction...

Active compounds derived from traditional Chinese medicine (TCM) hold considerable promise for drug development, owing to their natural origin and multi-target synergistic effects. However, their clinical translation has long been limited by poor aqueous solubility, low bioavailability, and inadequate targeting capacity. In recent years, carrier-free self-assembled nanomedicines have emerged as a promising strategy within the field of nano-enabled TCM. Driven by noncovalent interactions, such as hydrophobic forces, hydrogen bonding, and π-π stacking, these systems facilitate the spontaneous assembly of TCM-derived bioactive molecules into well-defined nanostructures. This approach can substantially improve drug loading efficiency, biocompatibility, and therapeutic synergy. This comprehensive review summarizes the underlying assembly mechanisms, key formulation parameters, and recent advances in the application of these nanostructures across antitumor, antibacterial, and anti-inflammatory therapies. It also discusses major challenges hindering large-scale production and clinical translation, including particle size control, stability, safety, and pharmacokinetic behavior. By integrating mechanistic insights with application outcomes and translational considerations, this comprehensive review aims to provide a comprehensive framework for the rational design of self-assembled TCM-based nanomedicines, thereby supporting the modernization of TCM and expanding its potential in innovative drug development.