Enhanced Electrochemical Characterization of the Immune Checkpoint Protein PD-L1 using Aptamer-Functionalized Magnetic Metal-Organic Frameworks.

ABSTRACT

Programmed death ligand 1 (PD-L1) is highly expressed in cancer cells and participates in the immune escape process of tumor cells. However, as one of the most promising biomarkers for cancer immunotherapy monitoring, the key problem ahead of practical usage is how to effectively improve the detection sensitivity of PD-L1. Herein, an electrochemical aptasensor for the evaluation of tumor immunotherapy is developed based on the immune checkpoint protein PD-L1. The fundamental principle of this method involves the utilization of DNA nanotetrahedron (NTH)-based capture probes and aptamer-modified magnetic metal-organic framework nanocomposites as signaling probes. A synergistic enhancement is observed in the electrocatalytic effect between Fe3O4 and UiO-66 porous shells in Fe3O4@UiO-66 nanocomposites. Therefore, the integration of aptamer-modified Fe3O4@UiO-66@Au with NTH-assisted target immobilization as an electrochemical sensing platform can significantly enhance sensitivity and specificity for target detection. This method enables the detection of targets at concentrations as low as 7.76 pg mL-1 over a wide linear range (0.01 to 1000 ng mL-1). The authors have successfully employed this sensor for in situ characterization of PD-L1 on the cell surface and for monitoring changes in PD-L1 expression during drug therapy, providing a cost-effective yet robust alternative to highly expensive and expertise-dependent flow cytometry.