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 <b><u>c</u></b>urvature and <b><u>a</u></b>ntigen-mediated <b><u>p</u></b>roximity ligation assay for <b><u>tu</u></b>mo<b><u>r</u></b>-derived <b><u>e</u></b>xosomes (<b>CAPTURE</b>) 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.