Emerging biomedical imaging applications of tumor-derived extracellular vesicles for premetastatic niche detection: Biological rationale, engineering strategies, and translational challenges

Abstract

Extracellular vesicles (EVs) are a heterogeneous population of membrane-enclosed nanoparticles naturally released by virtually all cell types, including exosomes, microvesicles, and other vesicular subtypes that differ in biogenesis, size, and molecular composition. By transporting proteins, lipids, nucleic acids, and metabolites, EVs mediate local and systemic intercellular communication and play a central role in tumor progression, organ-specific metastasis, and remodeling of distant microenvironments. Recent advances in EV isolation, engineering, and molecular profiling have accelerated interest in their use as nanomedicine platforms for both targeted delivery and cancer diagnostics. In particular, tumor-derived EVs (TEVs) exhibit intrinsic organotropism and participate in the establishment of premetastatic niches, making them promising vehicles for the targeted delivery of imaging probes to metastasis-prone tissues. This review discusses the emerging use of EVs as carriers of contrast and molecular imaging agents to enable visualization of premetastatic niches before overt metastatic lesions become detectable by conventional imaging modalities such as computed tomography. We highlight the biological rationale, engineering strategies, imaging applications, and translational challenges associated with EV-based probe delivery and consider how this approach may improve early detection of metastatic spread, risk stratification, and disease monitoring in oncology.