Monitoring of circulating exosomal immuno checkpoint in tumor microenvironment through ultrasensitive aptamer-functionalized SERS probes

Abstract

The exosomal programmed death ligand (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 could be measured on circulating malignant exosomes by making it “sandwich” between CD63 targeting magnetic probes and PD-L1 targeting SERS tags. Accordingly, the aptasensor could quantify the PD-L1 with limit of detection (LOD) reaching 4.31 ag/mL. Interestingly, the SERS-aptasensor demonstrated much higher sensitivity than standard ELISA method in quantifying time-dependent PD-L1 variations in MC38 treated mice model. The viability of the SERS-aptasensor was further validated by analyzing raw serum samples using confocal and portable Raman systems which indicated 98% diagnostic accuracy. 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 immunotherapies.

Keywords

• Surface-enhanced Raman spectroscopy (SERS)
• Aptamer
• PD-L1
• Biomarker
• Exosomes