Personalized detection of circling exosomal PD-L1 based on Fe₃O₄@TiO₂ isolation and SERS immunoassay

Circling exosomal PD-L1 can be expected as a predictor for the clinical responds of anti-PD-1/PD-L1 therapy. Here, we present a simple method integrating capture and analysis of exosomal PD-L1 directly from serum. Firstly, Fe₃O₄@TiO₂ nanoparticles were used to enrich exosomes through the binding of TiO₂ shell and hydrophilic phosphate head of the exosome phospholipids. Model exosomes can be enriched and separated from solution within 5 min with a capture efficiency of 96.5%. Secondly, anti-PD-L1 antibody modified Au@Ag@MBA SERS tags were added to label the exosomal PD-L1 for quantification. The whole process can be finished within 40 min with a detection limit of 1 PD-L1⁺exosome/μL. Furthermore, this method was used for personalized exosomal PD-L1quantification by using a 4 μL clinical serum sample individually. Based on the personalized SERS signal analysis, NSCLC patients can be distinguished from the healthy controls easily. More important, the advantage of clearly individual quantification may help the doctor to discover the relationship of exosomal PD-L1 and the immnuotherapy responds in individual level.