Advancements in cancer stem cell therapy: The effective integration of traditional Chinese medicine and nanotechnology.

Cancer stem cells (CSCs) play a pivotal role in cancer initiation, development, metastasis, and recurrence. They exhibit inherent resistance to conventional chemotherapy, posing a significant challenge to the complete eradication of tumors. Traditional Chinese medicine (TCM) and its bioactive compounds exhibit remarkable potential in selectively targeting cancer stem cells owing to their low toxicity and ability to regulate multiple molecular targets. In this review, we provide a comprehensive analysis of the biological characteristics of cancer stem cells and their role in tumor initiation and progression. We also evaluate therapeutic strategies targeting cancer stem cells and recent core molecular mechanisms, and highlight their limitations. Additionally, we explore the molecular mechanisms through which TCM active components (such as curcumin, berberine, and resveratrol) effectively target cancer stem cells via seven distinct pathways, as well as the multi-level, multi-mechanistic targeting of TCM on CSCs. Furthermore, we propose fabricating nanomedicines to solve the challenges of low bioavailability and insufficient targeting of active components in TCM. These nanomedicines, such as physically loaded nanomedicines, covalently coupled nanomedicines, and self-assembled nanomedicines, can precisely target drugs, enhance stability, and promote the synergistic effect of multiple components, thereby significantly improving the clearance efficiency of cancer stem cells. Finally, we explore the potential of intelligent-responsive nanomedicines and multimodal combination therapies in addressing tumor heterogeneity and advancing clinical translation. This will provide a theoretical foundation and methodological framework for integrating traditional medicine with modern technology.