Traditional Chinese medicine-based self-assembled nanomaterials for cancer therapy.

Traditional Chinese medicines (TCM) consist of raw herbs and herbal extracts with a plethora of documented beneficial bioactivities, which can combat tumors by immune modulation, apoptosis induction, and tumor microenvironment (TME) regulation. However, challenges like poor solubility, low bioavailability, and off-target effects limit their therapeutic potential. Alternatively, active ingredients derived from TCM contain modifiable groups, multiple active sites, hydrophobic side chains, and a rigid structural backbone. These inherent self-assembly properties can be exploited to construct self-assembled nanomaterials such as micelles, vesicles and hydrogels etc. Notably, these TCM-based nanomaterials can be further engineered with TME-responsive linkages to co-deliver chemotherapeutic and immunotherapeutic agents, achieving spatiotemporally controlled drug release with enhanced therapeutic efficacy. Herein, the strategies of TME-responsive and self-assembly of seven classes of TCM (e.g., polyphenols, quinones, monosaccharides, saponins, alkaloids, phytosterols, and terpenoids) are highlighted, offering insights into their potential applications in tumor therapy. Finally, we also discuss the clinical trials of TCM-derived self-assembled nanomaterials and the challenges in clinical translation of natural small molecules self-assembled nanomaterials.