A peptide-based fluorescent bioprobe for EphA2-overexpressing tumor targeting and image-guided surgical resection

Fluorescence-guided surgery (FGS) is an emerging and highly promising surgical technique in clinic. Owing to its real-time and visual characteristics, it assists in achieving clear pictures on lesion site, tumor boundary and degree of metastasis, which will definitely improve surgery accuracy and minimize cancer recurrence as much as possible. Herein, we report a near-infrared fluorescent bioprobe, YK80, which utilizes a modified heptamethine cyanine dye as the fluorophore and a self-assembling peptide targeting Ephrin receptor A2 (EphA2) proteins as the ligand. The design strategy and the synthetic route to YK80 are described, and then optical properties, pharmacokinetics, binding affinity between YK80 and the protein are further investigated. YK80 shows high affinity (K_D ≈ 100 nM) with EphA2-expressing cancer cells and excellent targeting ability in mouse models bearing colorectal tumors. Meanwhile, indocyanine green (ICG), the commonly used non-targeted fluorescent contrast agent is employed as the comparison for in vivo experiments. However, ICG owns no such capability towards cancer cells or solid tumors. Thus, YK80 could potentially serve as a targeted contrast agent for image-guided surgery and this successful example will boost the development of medical imaging, surgical methods as well as translational medicine.