Abstract

Tumor recurrence and therapeutic resistance remain major obstacles in effective cancer management, largely 
driven by a small but highly resilient subpopulation of cells known as cancer stem cells (CSCs). These cells 
possess self-renewal capacity, multipotency, and heightened resistance to chemotherapy, radiotherapy, and 
immunotherapy, enabling tumor regrowth and metastasis even after apparent clinical remission. Conventional 
anticancer strategies often fail to eradicate CSCs due to poor targeting specificity, systemic toxicity, and an 
inability to overcome the protective tumor microenvironment. Biomimetic nanoparticles have emerged as a 
promising precision nanomedicine strategy to address these limitations by emulating natural biological 
structures such as cell membranes, lipoproteins, exosomes, and extracellular matrix components. By inheriting 
biological functionalities including immune evasion, homotypic targeting, and receptor-specific interactions, 
biomimetic nanoparticles enable selective delivery of therapeutic payloads to CSC niches. This review 
comprehensively examines the biological basis of CSC-driven tumor recurrence, the design principles of 
biomimetic nanoparticles, and their application in selectively targeting CSCs. We discuss advances in 
membrane-coated, ligand-functionalized, and microenvironment-responsive biomimetic systems, highlight 
preclinical evidence of efficacy in preventing tumor relapse, and analyze translational challenges. Collectively, 
biomimetic nanoparticles represent a powerful platform for durable cancer control through precise CSC 
targeting.