Engineered Exosomes as Smart Drug Carriers: Overcoming Biological Barriers in CNS and Cancer Therapy

Abstract

Engineered exosomes have emerged as transformative drug carriers, uniquely equipped to overcome biological barriers in central nervous system (CNS) disorders and cancer therapy. These natural extracellular vesicles, derived from cell membranes, offer inherent biocompatibility, low immunogenicity, and the ability to traverse physiological obstacles such as the blood–brain barrier (BBB) and dense tumor stroma. Recent advances in exosome engineering—including surface modification (e.g., ligand conjugation for receptor-mediated targeting) and cargo loading (siRNA, CRISPR-Cas systems, and chemotherapeutics)—have enhanced their precision and therapeutic utility. For CNS delivery, exosomes functionalized with brain-homing peptides (e.g., RVG or TfR ligands) have enabled the efficient transport of neuroprotective agents or gene-editing tools to treat Alzheimer’s disease or glioblastoma. In oncology, engineered exosomes loaded with tumor-suppressive miRNAs or immune checkpoint inhibitors exploit tumor microenvironment (TME) features, such as acidity or enzyme overexpression, for spatially controlled drug release. Furthermore, hybrid exosome–liposome systems and exosome–biomaterial composites are being explored to improve payload capacity and stability. Despite progress, challenges persist in scalable production, batch consistency, and regulatory standardization. This review critically evaluates engineering strategies, preclinical success, and translational hurdles while proposing innovations such as AI-driven exosome design and patient-derived exosome platforms for personalized therapy. By bridging nanotechnology and biomedicine, engineered exosomes can represent a paradigm shift in targeted drug delivery, offering safer and more effective solutions for historically intractable diseases.