Nano-biomaterials in cancer therapy: Advances in targeting and overcoming cancer stem cell resistance.

Background and purpose: Cancer remains a leading cause of death globally, with long-term treatment success hindered by metastasis, recurrence, and therapy resistance. A central driver of these limitations is cancer stem cells (CSCs) - a rare subpopulation of tumour cells endowed with self-renewal and differentiation potential. CSCs contribute critically to tumour progression, metastatic spread, and resistance to conventional therapies, yet no clinically validated strategies currently exist to accurately detect or selectively eliminate them. Review approach: The paper systematically examined the literature on CSC origin, phenotypic characterization, isolation techniques, and mechanisms underlying resistance, including dormancy, enhanced DNA repair, apoptosis evasion, and microenvironmental protection. Particular attention was given to recent advances in nanomaterial-based strategies - metallic, carbon, and organic nanocarriers, designed to improve CSC-specific drug delivery, reactive oxygen species generation, pathway inhibition, and modulation of the CSC niche. Key results: Current CSC markers and in vivo models remain ambiguous and poorly standardized, limiting translational progress. Nanotechnology provides promising solutions by enabling targeted delivery and multi-functional therapy integration, yet most systems are still at the preclinical stage, constrained by issues of biocompatibility, targeting precision, and manufacturing scalability. Conclusion: Multifunctional nanoplatforms hold substantial potential to overcome CSC-driven resistance, improve therapeutic selectivity, and reduce recurrence. However, rigorous optimization and clinical validation are essential before these technologies can be integrated into routine oncology. This review advances understanding by outlining the intersection of CSC biology and nanomedicine, emphasizing translational pathways for CSC-targeted cancer therapy.