Immuno-affinitive supramolecular magnetic nanoparticles incorporating cucurbit[8]uril-mediated ternary host-guest complexation structures for high-efficient small extracellular vesicle enrichment.

Enriching small extracellular vesicles (sEVs) with undamaged structure and function is a pivotal step for further applications in biological and clinical fields. It has prompted researchers to explore a carrier material that can efficiently capture sEVs while also gently release the captured sEVs. Here, 1-adamantylamine (1-ADA) responsive immuno-affinitive supramolecular magnetic nanoparticles (ISM-NPs) incorporating ternary host-guest complexation structures mediated by CB[8] were proposed to achieved the goal. In particular, the ternary host-guest complexation was constructed by the host molecule (cucurbit[8]uril, CB[8]) mediated assembly of two guest molecules (naphthol and bipyridine), and served as a cleavable bridge to connect the magnetic core and peripheral antibody. These constructed ISM-NPs performed well in the applications of capturing sEVs with a high capture efficiency of 85.5%. Further, the CB[8]-mediated ternary host-guest complexation structures can be disassembled with addition of the 1-ADA. Thus, the sEVs recognized by the anti-CD63 were released competitively, with a decent release efficiency more than 82%. The released sEVs kept intact morphology and exhibited appropriate size distribution and concentration. This supramolecular magnetic system, with 1-ADA responsive ternary host-guest complexation structures, may contribute to efficient enrichment of any other biomarkers, likely cells, proteins, peptides, etc.