A colorimetric biosensor for the analysis of circulating PD-L1 with application to diagnose breast cancer

Abstract

Increasing studies support the significant potential of circulating PD-L1 in diagnosing breast cancer and identifying the beneficiaries of immunotherapies. Consequently, developing available methods for the accurate detection of circulating PD-L1 has become increasingly important. In this study, we have developed a colorimetric biosensor for visual detection of circulating PD-L1 in the patients with triple-negative breast cancer (TNBC) based on target-activated satellite assembly of MOF-Fe₃O₄ nanoparticles. Specifically, the specific binding between PD-L1 and its aptamer can sequentially activate an enzyme-powered strand displacement amplification (E-SDA) system and a Fe-based metal-organic framework (Fe-MOF)-Fe₃O₄ nanoparticle assembly system. Due to the amplification function of the E-SDA system and the high peroxidase-like activity of Fe-MOFs, sensitive and colorimetric detection of serum-derived soluble PD-L1 and exosomal PD-L1 can be achieved with the limits of detection (LODs) of 5 pg/mL and 1 pg/mL, respectively. Using this flexible platform, it is revealed that the levels of soluble PD-L1 and exosomal PD-L1 can distinguish patients with breast cancer from healthy individuals and determine PD-L1 positivity. Comparatively, the expression levels of exosomal PD-L1 show higher consistency with that of tumor cells measured by immunohistochemistry. Therefore, these results suggest that our exploration provides a novel perspective for developing circulating PD-L1-based clinical diagnosis, enriching detection strategies for various forms of PD-L1, and advancing research in clinical diagnostic technique.