Breaking barriers: Extracellular vesicles as dual-agents in diagnosing and treating brain metastasis

Brain metastasis poses a formidable barrier in cancer management, characterized by delayed diagnosis and limited treatment options. Extracellular vesicles (EVs), nano-sized, lipid bilayer-bound particles secreted by virtually all cell types, have emerged as dual-functional agents with potential to revolutionize both diagnosis and treatment. Owing to their ability to cross the blood-brain barrier and circulate in bodily fluids, EVs serve as non-invasive reservoirs of tumor-derived biomarkers, offering new avenues for early and accurate diagnosis. Simultaneously, advances in EV engineering have enabled their use as targeted therapeutic vehicles capable of delivering chemotherapeutics, nucleic acids, or immunomodulators directly to metastatic brain lesions. Functionalization with brain-targeting ligands further enhances their specificity, reducing systemic toxicity and improving therapeutic precision. This review systematically explores the mechanistic roles of EVs in brain metastasis progression and highlights their transformative potential as both diagnostic tools and therapeutic nanocarriers, breaking current barriers in the clinical management of brain metastases.