Polydiacetylene-based aptasensors for rapid and specific colorimetric detection of malignant exosomes

Exosomes (50-150 nm) play significant biological functions in intercellular communication and transportation of diverse biomolecules, including proteins and nucleic acids. In particular, malignant exosomes have received a great deal of attention as possible indicators for cancer detection and treatment. To swiftly and precisely identify malignant exosomes from normal exosomes in diverse bodily fluids, we developed polydiacetylene (PDA)-based aptasensors with distinct optical features exhibiting color shift in response to biological recognition. To identify epithelial cell adhesion molecules (EpCAM) overexpressed on the surface of malignant exosomes, anti-EpCAM aptamer-conjugated diacetylene monomer (TCDA-Apt) was synthesized and used to create anti-EpCAM aptamer-conjugated PDA (anti-EpCAM Apt-PDA) vesicles. In just 15 min following the reaction with malignant exosomes, the anti-EpCAM Apt-PDA vesicles underwent a visible color change from blue to purple. They showed high specificity to EpCAM-positive malignant exosomes over non-malignant exosomes, bovine serum albumin (BSA), and fibrinogen. Moreover, its effectiveness in the point-of-care (POC) detection of malignant exosomes was evaluated using human sera. Therefore, our PDA-based aptasensors have tremendous potential for on-site cancer diagnosis.