Traditional Chinese medicine (TCM)-based nanoformulations for cancer therapy: antitumor mechanisms, challenges, and future directions.

Background/Objectives: Traditional Chinese medicine (TCM)-derived compounds have anticancer potential because of their multi-component, multi-target actions and generally favorable toxicity profiles. Clinical translation, however, is limited by poor aqueous solubility, rapid systemic metabolism, and insufficient tumor-selective delivery. This review critically evaluates recent TCM-based nanoformulations developed to address these limitations and improve the therapeutic performance. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and EQUATOR guidance, PubMed and Web of Science databases were searched for original studies published during the previous 5 years using terms including "TCM," "nanoformulation," and "anticancer." After screening 387 records, 81 studies covering 50 representative TCM compounds were included and assessed for the preparation methods, antitumor mechanisms, and translational barriers. Results: Relative to free compounds, nanoformulations frequently improved solubility, stability, apparent bioavailability, or the targeting efficiency of TCM constituents. Reported mechanisms included apoptosis, cell-cycle arrest, ferroptosis, immunogenic cell death, and tumor-microenvironment remodeling across breast, lung, colorectal, and other cancer models. Nevertheless, most evidence was derived from Conclusion: TCM-based nanoformulations represent a promising strategy for integrating traditional herbal medicine with modern cancer therapy. Despite these promising findings, substantial challenges remain in standardization, reproducibility, pharmacokinetics, long-term safety, manufacturing, and clinical validation. Future studies should prioritize head-to-head comparisons, quantitative biodistribution, clinically relevant models, and scalable manufacturing.