Advances in Nanomedicine for Targeting Cancer Stem Cells and Overcoming Therapeutic Resistance

Cancer stem cells (CSCs), a rare and specialized subset of tumor cells, are central to tumor initiation, progression, and therapy resistance. Their capacities for self-renewal, differentiation, and metabolic adaptation not only drive intratumoral heterogeneity but also enable therapeutic evasion, contributing to tumor recurrence and metastasis. Advances in biomaterials, particularly functionalized nanomedicines, have introduced strategies that precisely target CSCs by reaching their niches, disrupting key signaling pathways, and enhancing drug delivery specificity. These multifaceted approaches hold promise for overcoming therapy resistance and achieving durable treatment outcomes. Understanding the biological characteristics of CSCs, including the signaling pathways that regulate stemness, their interactions with the tumor microenvironment, and the mechanisms underlying therapy resistance, is critical for identifying potential therapeutic targets. Recent developments in CSC biology and nanomedicine-based interventions have yielded important insights, enabling the design of precision therapies specifically targeting CSC eradication. In this review, we comprehensively examine these advancements, emphasizing advances in nanomedicine design, therapeutic strategies, and persistent challenges in tackling CSC-related resistance. We also explore future directions for integrating nanotechnology into precision oncology, providing insights into addressing translational barriers and developing effective treatments that reduce recurrence and enhance patient survival.