A novel drug screening strategy based on non-invasive electrochemical detection of multiple tumor markers secreted by patient-derived microgel organoids

Abstract Rapid and effective drug screening is a key step for personalized cancer therapy. Recently, microgel organoids have emerged as a promising in vitro drug screening model that ensures not only the uniform manufacture, but also the integration of various cells, active factors and matrix materials to mimic the real 3D tumor tissue. However, their corresponding drug sensitivity and efficacy analysis remains challenging, since traditional optical methods are invasive/destructive to tumor organoids and thus require many clinical samples for drug screening. Herein we propose a novel strategy based on non-invasive electrochemical detection of multiple tumor markers secreted by patient-derived microgel organoids. Specifically, a detection electrode is constructed using Ti ₃ C ₂ MXene, Au nanoparticles (AuNPs) and aptamers (conjugated with redox probes) to detect breast cancer biomarkers through the specific recognition between aptamer and biomarkers. Our data reveal that high sensitivity and specificity of biomarker sensing can be both achieved for drug screening models prepared using breast cancer cell line, clinical breast cancer and colorectal cancer samples, which can be converted into relative cell viability and half-maximal inhibition concentration (IC ₅₀ ). Similar results between optical and electrochemical methods prove the feasibility and potential application of our strategy in high-throughput drug screening for diverse cancers.