Overcoming Epithelial–Mesenchymal Transition Challenges in Cancer Detection through a Dual-Targeting Strategy

Epithelial cellular adhesion molecules (EpCAM), highly expressed antigens on cancer cell surfaces, are crucial biomarkers for tumor diagnosis and therapy. Despite its utility, the efficiency of EpCAM-targeting recognition technologies is often limited by its downregulation during epithelial-mesenchymal transition (EMT) and variability across cancer types. To address these challenges, we engineered bispecific aptamers to create a new molecular cancer recognition probe (BAptP) that simultaneously targets EpCAM and CD71. This study demonstrates that BAptP can bind to various cancer cells and form stable targeting ligand-receptor complexes at low concentrations. In vitro studies confirm that the BAptP probe specifically recognizes different types of tumor cells in complex physiological environments, indicating its potential as a molecular diagnostic tool in clinical investigations. Additionally, in vivo fluorescence imaging reveals that bispecific BAptP achieves higher tumor accumulation and longer retention compared with monovalent aptamers, showcasing its potential for precision tumor therapy.