Nanomedicine and nutraceutical-based nanocarriers for specific delivery to cancer stem cells: targeted drug delivery at the STEM frontier

Cancer stem cells (CSCs) represent a highly plastic and therapy-resistant subpopulation within tumors, driving tumor initiation, progression, metastasis, and relapse. Their ability to evade conventional treatments necessitates novel, highly specific therapeutic strategies. Nanomedicine offers a transformative approach to overcome the limitations of traditional therapies by enabling targeted and controlled drug delivery. This review explores the synergistic potential of combining advanced nanocarriers with potent nutraceuticals, emphasizing their capacity to modulate critical CSC signaling pathways and overcome inherent bioavailability challenges. The review first outlines the unique biological characteristics of CSCs that make them elusive therapeutic targets. It then delineates the principles of nanomedicine for precise drug delivery and details the anti-CSC mechanisms of various promising nutraceuticals. Furthermore, it examines innovative nanocarrier-based strategies designed for specific CSC targeting, such as curcumin-loaded solid lipid nanoparticles and resveratrol-hydrogels, presenting compelling preclinical evidence. Finally, the report addresses the significant translational challenges that must be overcome for these advanced therapies to reach clinical fruition, underscoring the transformative potential of emerging technologies, such as biomimetics, microfluidics, and artificial intelligence, in advancing targeted CSC therapies at the “STEM Frontier” of oncology.