Traditional Chinese medicine-mediated ferroptosis in cancer therapy: mechanisms, advances, and nanotechnology-driven delivery strategies

Cancer remains a life-threatening disease that poses a significant global health burden. Conventional treatments such as surgery, radiotherapy, chemotherapy, and targeted therapy have shown efficacy but remain limited in their effectiveness. Ferroptosis, to which various tumor cells are highly sensitive, is a novel iron-dependent mode of cell death triggered by excessive accumulation of lipid peroxide within cells, and is a potential target for cancer therapy. Traditional Chinese Medicine (TCM), with its unique advantages, including multi-component, multi-target mechanisms, and multi-pathway characteristics, has made remarkable progress in regulating ferroptosis of cancer in recent years. However, their clinical application is hindered by poor water solubility, low bioavailability and other limitations. On the other hand, the rapid advancement of nanotechnology has emerged as a promising strategy for significantly enhancing the therapeutic efficacy of TCM in modulating ferroptosis. This review aims to summarize recent advances in TCM-based strategies for regulating ferroptosis to enhance the antitumor efficacy. First, we outlined the core mechanisms of ferroptosis. Next, we highlighted the progress of TCM in inducing ferroptosis of tumor. Furthermore, we examined recent advances in precise ferroptosis modulation through nano-drug delivery systems. Finally, the current challenges and future perspectives were also discussed, aiming to provide a theoretical foundation and practical guidance for developing ferroptosis-driven TCM therapeutics.