Size Matters: Curvature and Antigen-Mediated Dual Recognition of Size-Specific Tumor-Derived Exosomes

Accurate identification of tumor-derived exosomes is crucial for advancing cancer diagnosis and therapies. However, distinguishing tumor-derived exosomes is challenging due to the heterogeneity of exosomes, which reflect different sizes and cells of origin. To address this challenge, we introduce the curvature and antigen-mediated proximity ligation assay for tumor-derived exosomes (CAPTURE) strategy, which leverages the size-selective properties of curvature-sensing peptides and specific antigen binding of aptamers. CAPTURE enables highly specific identification and precise quantification of the PD-L1⁺ exosomes in plasma samples. CAPTURE is proven to be simple, homogeneous, rapid, and highly selective, achieving a 100% specificity in discriminating colorectal cancer (CRC) patients from healthy donors. Overall, the CAPTURE strategy presents a promising avenue for precise and noninvasive cancer diagnosis.