Monitoring of Circulating Exosomal Immuno Checkpoint in Tumor Microenvironment Through Ultrasensitive Aptamer-Functionalized Sers Probes

The exosomal programmed death ligand-1 (PD-L1) and its combination with receptor PD-1 is pivotal in microtumor environment which favors the metastasis and impairs the natural immune system. We proposed a SERS-aptasensing techniques through which PD-L1 is quantified on circulating malignant exosomes by making it “sandwich” between CD63 targeting magnetic probes and PD-L1 targeting SERS tags. Accordingly, the aptasensors quantified the PD-L1 in the 6 ag/mL to 0.6 pg/mL range with limit of detection (LOD) reaching 4.31 ag/mL. Interestingly, the SERS-aptasensors demonstrated the superior sensitivity than standard ELISA method by quantifying time-dependent variations in PD-L1 in MC38 treated mice model. The SERS-aptasensor further validated the viability by analyzing raw serum samples using confocal and portable Raman systems which indicated nearly 98% diagnostic sensitivity. Collectively, our study reveals the ability of using aptamer-SERS method to quantify the PD-L1 in serum, suggesting an alternative promising strategy to monitor the efficacy of PD-L1/PD-1 based immunotherapies.