Post-functionalized ZIF-8 for high-performance synergistic isolation of extracellular vesicles via co-precipitation

Extracellular vesicles (EVs) and their cargos are increasingly being recognized as noninvasive diagnostic markers. The isolation of EVs from complex biological samples is crucial for subsequent analysis. Herein, a distearoyl phospholipid ethanolamine-functionalized zeolitic imidazolate framework (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 EV isolating selectivity. Benefitting from this feature, it could be well compatible with the analysis of RNA and proteins in EVs. Furthermore, the ZIF-8-DSPE was utilized to isolate EVs from clinical plasma of primary colorectal cancer (CRC) patients, CRC patients with liver metastases (CRCLM) and healthy donors (HD). Proteomics results illustrated that 11 proteins were up-regulated in the CRCLM group compared to the CRC group, and 59 proteins were upregulated in the CRC group compared to the HD group. Furthermore, some proteins such as PRDX2, TFP1, FGG and F13A1 were found to be closely related to CRC progression and metastasis, and have the potential to be biomarkers for CRC. These findings proposed that it is a promising strategy to identify biomarkers from plasma EVs for early detection and disease monitoring of CRC.