Engineered exosomes as natural nanocarriers for precision drug and gene delivery in cancer therapy

Abstract Precision cancer therapy requires delivery systems capable of selective targeting, effective cargo protection, and sustained performance in complex biological environments. Engineered exosomes have emerged as promising nanocarriers because they combine biological compatibility, membrane-mediated cargo protection, and the capacity to transport nucleic acids, proteins, and small-molecule drugs. This review critically examines recent advances in engineered exosomes for precision drug and gene delivery in cancer therapy, with emphasis on donor-cell selection, cargo-loading strategies, targeting mechanisms, and translational challenges. Current evidence indicates that endogenous loading approaches, including donor-cell transfection and genetic engineering, are generally more compatible with exosome biogenesis and cargo stability, whereas exogenous methods such as electroporation, sonication, extrusion, and hybrid loading offer greater flexibility but may compromise vesicle integrity and post-loading functionality. Targeting efficiency depends not only on ligand-mediated recognition and surface engineering, but also on major in vivo barriers, including rapid mononuclear phagocyte system clearance, vascular constraints, and tumor microenvironment heterogeneity. The clinical translation of exosome-based therapeutics remains limited by donor-dependent heterogeneity, incomplete quality-control frameworks, manufacturing standardization, and regulatory uncertainty, particularly when compared with the greater industrial maturity of lipid nanoparticles. Engineered exosomes remain highly attractive for applications in which biological tropism, complex cargo delivery, and immune-modulatory functionality provide advantages that synthetic systems do not readily replicate. Progress in this field will depend on mechanism-guided loading strategies, robust quality metrics, scalable manufacturing, and clinically interpretable potency assessment.