Functional Three-Dimensional Zeolitic Imidazolate Framework with an Ordered Macroporous Structure for the Isolation of Extracellular Vesicles

Extracellular vesicles (EVs) and their cargoes are increasingly being recognized as noninvasive diagnostic markers, necessitating the isolation of EVs from complex biological samples. Herein, a distearoyl phospholipid ethanolamine-functionalized single-crystal ordered macroporous three-dimensional zeolitic imidazolate framework (SOM-ZIF-8-DSPE) was developed, which combines the surface charge interaction of ZIF-8 with the synergistic effect of DSPE insertion into the phospholipid membrane of EVs to improve the isolating selectivity of EV capture. The materials have porous structures larger than 300 nm in diameter, providing enough space and active sites to trap EVs. Benefiting from this feature, the entire isolation process takes only 10 min and is well compatible with the subsequent analysis of RNA in EVs. Consequently, 10 upregulated miRNA of plasma EVs in the primary colorectal cancer (pCRC) patients is found over the healthy donors, and 6 upregulated miRNA of plasma EVs in the metastatic colorectal cancer (mCRC) patients over pCRC patients. These findings suggest that the isolation of EV-based SOM-ZIF-8-DSPE is a promising strategy to identify biomarkers for disease diagnosis, such as miRNAs in plasma EVs for the early detection of CRC.