Nanotechnology-enabled precision targeting of lung cancer stem cells: Recent developments and therapeutic...

Lung cancer remains one of the leading causes of cancer-related mortality worldwide, highlighting the urgent need for more effective therapeutic strategies. Lung cancer stem cells (LCSCs) play critical roles in tumor initiation, metastasis, therapeutic resistance, and recurrence through dynamic interactions with the tumor microenvironment (TME), metabolic reprogramming, and immune evasion. Despite advances in targeted therapy and immunotherapy, conventional approaches remain insufficient for the complete elimination of LCSCs. Recent progress in nanotechnology has provided new opportunities for precision targeting of LCSCs by enhancing drug bioavailability, tumor selectivity, controlled release, and multifunctional therapeutic integration. In this review, we summarize current nanotechnology-enabled strategies targeting LCSCs, with particular emphasis on TME remodeling, metabolic regulation, and tumor immunity. Distinct from previous reviews that discuss cancer stem cells or nanomedicine separately, this review establishes an integrated framework linking LCSC niche regulation with nanotechnology-based precision therapeutics in lung cancer. We further highlight the therapeutic potential of multifunctional nanoplatforms, including nanocrystalline drugs, smart nanocarriers, and combinational nano-delivery systems, in modulating stemness-associated pathways, overcoming immune suppression, and disrupting metabolic adaptation. In addition, emerging strategies involving stimulus-responsive nanomaterials, ferroptosis induction, and engineered immunotherapeutic platforms are discussed. Finally, current challenges and future perspectives regarding tumor heterogeneity, nanocarrier biocompatibility, translational feasibility, and personalized therapeutic design are addressed. Collectively, this review provides a comprehensive perspective on nanotechnology-enabled precision targeting of LCSCs and offers insights into next-generation therapeutic strategies for lung cancer.