Recent Advances on Extracellular Vesicles: A Natural Nanomaterial for Biomedical Application

Extracellular vesicles (EVs), naturally secreted by cells as nanoscale lipid bilayer structures, have become a research hotspot in biomedicine owing to their excellent biocompatibility, low immunogenicity, and inherent ability to cross biological barriers. This review systematically summarizes recent advances in EVs as natural nanomaterials. The biogenesis mechanisms of EVs are outlined, followed by a comparative analysis of the advantages and limitations of mainstream isolation and purification methods, including ultracentrifugation, size-exclusion chromatography, and microfluidic technologies. The core guiding role of the MISEV 2023 guidelines in standardizing EV characterization is highlighted. Engineering strategies to enhance EV therapeutic efficacy-including parental cell modification, post-isolation physicochemical tailoring, and hybrid vesicle construction-are then reviewed, followed by a comparative analysis of mainstream isolation technologies, emphasizing the trade-offs between purity and yield. Distinct from conventional descriptive reviews, this article establishes a strong biomimetic framework to scrutinize engineering strategies, including parental cell genetic modification, post-isolation physicochemical tailoring, and the fabrication of hybrid bio-synthetic vesicles. The design principles governing targeted delivery, drug-loading physics, and in vivo pharmacokinetic stability are critically evaluated through the lens of biomimetic nanotechnology. Furthermore, we identify critical research gaps and technical bottlenecks impeding clinical translation, offering a forward-looking perspective on the evolution of EVs from natural messengers into standardized precision medicine platforms.