A self-accelerated responsive fluorescent sensor for rapid and specific cancer biomarker EpCAM detection and cancer imaging in vivo

The detection and in-situ fluorescence imaging of cancer biomarkers are crucial for early cancer diagnosis, progression and treatment informing as well as prognosis evaluation. Epithelial cell adhesion molecule (EpCAM) is a protein-based cancer biomarker that has been affirmed as an attractive target for epithelioid cancer diagnosis and therapy. Current fluorescence sensors for EpCAM are limited by either being “always on” or sensing and imaging only in living cells, leading to high background interference or restricted practicability. In this study, a simple yet effective APN sensor based on aptamer-conjoined polydiacetylene nanoliposomes was developed for near-infrared (NIR) fluorescence turn-on sensing of EpCAM. Multiple electrostatic and noncovalent interactions among EpCAM, the aptamer and cationic polydiacetylene (PDA) nanoliposomes in the system synergistically produced a self-accelerated effect that enabled detection of EpCAM within few minutes with high sensitivity and selectivity. Our APN sensor could also realize the quantification and in-situ mapping of EpCAM in targeted cancer cells. Bioimaging studies in tumor-bearing mice modes further demonstrated the capability of APN sensor as an excellent imaging agent for sustained EpCAM-targeted cancer imaging in vivo. Additionally, APN sensor was further employed to delineate the cancer lesions in pathological sections from patients with breast cancer, showing favorable differentiating ability. Thus, our strategy not only establishes an appealing alternative for EpCAM sensing and targeted cancer imaging but also provides a universal sensing platform applicable to design sensors for other disease biomarkers.