Exosomes serve as natural nanocarriers targeting cancer stem cells to advance precision oncology

Cancer stem cells (CSCs) represent a formidable challenge in oncology, serving as the primary drivers of tumor initiation, progression, metastasis, and, critically, therapeutic resistance and recurrence. Their inherent self-renewal capacity and phenotypic plasticity enable them to evade conventional treatments, necessitating novel therapeutic strategies. Extracellular vesicles (EVs), particularly exosomes, have emerged as pivotal mediators of intercellular communication within the tumor microenvironment (TME), carrying a diverse cargo of proteins, lipids, and nucleic acids that profoundly influence cellular behavior. This review synthesizes the current understanding of exosome biogenesis and cargo loading, highlighting their natural advantages as nanocarriers due to their low immunogenicity, high biocompatibility, and intrinsic ability to traverse biological barriers. It further explores the intricate roles of tumor-derived exosomes in fostering cancer progression and maintaining CSC properties by modulating the TME and promoting immune evasion. Crucially, this report delves into the burgeoning field of exosome- and EV-based CSC targeting, detailing strategies that leverage both naturally occurring and engineered exosomes for precise drug delivery, gene therapy, and immunomodulation. While significant challenges persist in large-scale production, isolation, cargo loading efficiency, and regulatory standardization, the transformative potential of engineered exosomes for targeted CSC eradication is immense. Future directions emphasize advanced bioengineering, multi-modal therapeutic combinations, and rigorous clinical translation to unlock the full promise of exosome-based therapies in achieving durable remissions and improving patient outcomes.