Emerging phospholipid-targeted affinity materials for extracellular vesicle isolation and molecular profiling

Extracellular vesicles (EVs) carrying lipids, proteins, nucleic acids and small molecular metabolites have emerged as an attractive paradigm for understanding and interfering physiological and pathological processes. To this end, selective and efficient separation approaches are highly demanded to obtain target EVs from complicated biosamples. With increasing knowledges on EV lipids, recent years have witnessed rapid advances of phospholipid-targeted affinity materials and platforms for high-performance isolation and analysis of EVs. In view of this, this review is contributed to introduce recent progresses in lipid membrane-targeted affinity strategies for EV isolation and molecular detection in biofluids. Affinity ligands including lipids, peptides, small molecules and aptamers and their molecular interactions with lipids are discussed in focus. The design, construction and mechanism of actions of affinity interfaces are summarized. The EV separation performances in complex biosamples and downstream proteomic, lipidomic and metabolic profiling are introduced. Finally, the perspectives and challenges for the development of next-generation phospholipid-targeted EV separation platforms are discussed.