Carrier-free self-assembled nanomedicines from natural small molecules: advances and perspectives for disease treatment

Carrier-free self-assembled nanomedicines (CFSNs) derived from natural small molecules (NSMs) have garnered significant attention in the field of nanomedicine due to their unique properties and potential therapeutic applications. This review provides an in-depth analysis of the recent advances in the development and application of CFSNs for disease treatment. We discuss the self-assembly mechanisms of NSMs, such as polyphenols, alkaloid, and terpenoid, which form stable and biocompatible nanoscale structures without the need for synthetic carriers. The fundamental forces driving self-assembly, including hydrogen bonding, π-π stacking interactions, electrostatic interactions, and coordination interactions, are elucidated in the first section. These CFSNs exhibit enhanced solubility, improved pharmacokinetics, and reduced toxicity compared to their bulk counterparts. The therapeutic potential of CFSNs is evaluated across various disease models, including cancer, infection, inflammation, cardiovascular diseases, and neurodegenerative disorders. We also address the challenges associated with the clinical translation of CFSNs, such as scalability, reproducibility, and regulatory approval. Finally, we offer perspectives on future research directions, emphasizing the need for interdisciplinary collaboration to fully harness the therapeutic potential of CFSNs. This comprehensive overview aims to provide a foundation for further exploration and development of CFSNs as a promising platform for next-generation nanotherapeutics.