Cancer stem cells (CSCs) represent a distinct subpopulation within tumors, intricately linked to tumorigenesis, progression, drug resistance, recurrence, and metastasis. Therefore, targeting CSCs is essential for achieving a definitive cure for cancer. The concomitant administration of two drugs, aimed at both tumor cells and CSCs, presents a promising strategy for the comprehensive eradication of tumors. However, ensuring the synergistic efficacy and targeted delivery of these dual drugs at the tumor site remains a significant challenge. This review begins by elucidating the biological characteristics of CSCs, with a particular focus on their differentiation and self-renewal capabilities. It then provides a comprehensive overview of common therapeutic approaches targeting CSCs, highlighting the benefits of dual-drug combination therapy. The subsequent sections concentrate on the application of dual-drug delivery systems in CSC therapy, detailing various dual drug-loading strategies, including co-loading at the same site, loading at different sites, physical mixing, and self-assembly. Additionally, it also summarizes multimodal treatment strategies that integrate dual-drug delivery systems with other therapeutic modalities. Finally, the challenges associated with dual-drug delivery systems in CSC therapy are discussed, along with potential future developments in this field. This review aims to offer a theoretical foundation and methodological reference for the treatment of CSCs, ultimately contributing to the overarching goal of curing cancer.
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