Abstract

Cancer stem cells (CSCs) represent a subpopulation of tumor cells with self-renewal and tumor-initiating 
properties, playing a central role in tumor recurrence, metastasis, and resistance to conventional therapies. 
Despite advances in cancer treatment, targeting CSCs remains a significant challenge due to their plasticity, 
quiescent nature, and resistance mechanisms. Nanotechnology offers an innovative platform for the targeted 
delivery of therapeutics to CSCs by exploiting unique features such as enhanced permeability and retention 
(EPR) effect, surface functionalization, and controlled drug release. This review critically discusses the biology 
of CSCs, current strategies to target them, and the application of nanotechnology-based approaches, including 
nanoparticles, liposomes, micelles, dendrimers, and exosomes, to overcome the limitations of conventional 
therapies. We highlight the design considerations for CSC-specific targeting, recent preclinical and clinical 
advances, and the integration of molecular markers, such as CD44, CD133, ALDH1, and EpCAM, for precise 
targeting. Furthermore, we examine the major challenges, including off-target effects, heterogeneity of CSCs, 
and translational bottlenecks, as well as future opportunities such as smart nanocarriers, combination therapies, 
and personalized nanomedicine. Overall, nanotechnology presents a promising frontier in eliminating CSCs and 
improving long-term cancer treatment outcomes.