PD-L1 exosomes electrochemical sensor based on coordination of AgNCs and Zr4+: Multivalent peptide enhancing target capture efficiency and antifouling performance.

Programmed death ligand 1 (PD-L1) exosomes are important biomarkers of immune activation in the initial stages of treatment and can predict clinical responses to PD-1 blockade in various cancer patients. However, traditional PD-L1 exosome bioassays face challenges such as high interface fouling in complex detection environments, limited detection specificity, and poor clinical serum applicability. Inspired by the multi-branched structure of trees, a biomimetic tree-like multifunctional antifouling peptide (TMAP)-assisted electrochemical sensor was developed for high-sensitivity exosomes detection. Multivalent interaction of TMAP significantly enhances the binding affinity of PD-L1 exosomes, thanks to the designed branch antifouling sequence, TMAPs antifouling performance is further improved. The addition of Zr4+ forms coordination bonds with the exosome's lipid bilayer phosphate groups to achieve highly selective and stable binding without interference from protein activity. The specific coordination between AgNCs and Zr4+ contributes to a dramatic change in the electrochemical signals, and lowing detection limit. The designed electrochemical sensor exhibited excellent selectivity and a wide dynamic response within the PD-L1 exosome concentration range from 78 to 7.8 × 107 particles/mL. Overall, the multivalent binding ability of TMAP and the signal amplification characteristics of AgNCs have a certain driving role in achieving clinical detection of exosomes.