Aptamer-based technologies for extracellular vesicle analysis and engineering: from isolation to functional applications

Extracellular vesicles (EVs) are natural mediators of intercellular communication and hold promise for disease diagnosis and drug delivery, yet their intrinsic heterogeneity complicates isolation, molecular profiling, and targeted delivery. Aptamers, owing to their high affinity, specificity, chemical tunability, and scalable synthesis, offer a flexible molecular toolkit to address these challenges. In this review, we highlight recent progress in integrating aptamers into EV research across three interconnected domains: (1) the selection of aptamers against EV-associated surface markers; (2) the development of aptamer-based methods for EV capture and isolation; (3) the use of aptamer-functionalized EVs for targeted drug delivery and immunomodulation. We also discuss outstanding challenges, particularly the need for selection strategies that better preserve native EV epitope conformations and the rational design of multifunctional aptamer architectures. Looking forward, the convergence of aptamer technology with EV biology is expected to enable aptamer-drug conjugates and minimally invasive, dynamic liquid biopsy approaches for major diseases such as cancer, ultimately advancing early diagnosis and precision medicine.