From cellular debris to intelligent therapeutics: recent advances and emerging paradigms in extracellular vesicle-based nanomedicine, highlighting technological improvements and clinical prospects

Extracellular vesicles (EVs) participate in numerous fundamental biological processes, making them highly promising candidates for applications in nanomedicine, regenerative medicine, and diagnostics. Owing to their intrinsic biocompatibility, molecular complexity, and selective targeting capabilities, EVs have already been investigated extensively in both preclinical and clinical studies for therapeutic purposes. The review first outlines the evolution of EVs research, followed by an examination of their intrinsic features and heterogeneity as both a defining feature and a flaw for EV-based therapeutics. Established and emerging single-particle characterization techniques are critically discussed, with particular emphasis on current limitations related to standardization and reproducibility. The translational potential of EVs is subsequently explored in the context of drug delivery and targeting, regenerative medicine, biomarker discovery, and diagnostic applications. The final sections highlight the growing clinical landscape of EV-based therapeutic interventions and discuss the integration of artificial intelligence approaches for predictive modeling and optimization of EV engineering and targeting strategies. Overall, this review illustrates how advances in bioengineering, analytical technologies, and data-driven methodologies are converging to support the development of personalized, scalable, and clinically translatable extracellular vesicle-based therapeutics.