Facile Synthesis of Bifunctional Metal–Organic Framework Nanoparticles for Isolation of Extracellular Vesicles

Extracellular vesicles (EVs) play a vital role in mediating cell communication by transferring their contained constituents. The field of EV studies continues to attract popular interests due to the pathophysiological function and clinical application values of EVs. Various kinds of materials have been developed to isolate EVs from complex biological samples. In this work, we develop a two-step “green” strategy to prepare a distearoyl phospholipid ethanolamine (DSPE) functionalized UiO-66 metal–organic framework (MOF) nanomaterial with water as the solvent at room temperature (RT). This synthesized process was facile, simple, safe, economical, environmentally friendly, and sustainable. The obtained UiO-66-DSPE material could be applied to efficiently enrich EVs from a cell medium and urinary samples by taking advantages of the affinity interaction of Zr4+ and the synergistic effect of DSPE insertion toward the phospholipid membrane of EVs. More than 99% of captured EVs could be released by alkaline elution, and the eluted EVs could maintain their structural integrity and biological activity. Furthermore, 112 upregulated proteins and 45 downregulated proteins were identified by comparing the urinary EVs of colorectal cancer (CRC) patients with those of healthy donors, and some of them were closely related to the CRC progression. These results indicated that the EV isolation method based on the bifunctional UiO-66-DSPE nanoparticles might provide a potential approach in the further analysis of EVs for cancer diagnosis.