Self-adaptive non-covalent albumin-binding near-infrared probe conjugates enabling precise sentinel lymph node metastasis illumination and primary tumor imaging

Tumor sentinel lymph node (SLN) metastasis plays a vital role in tumor staging and therapeutic decision-making process. However, precise diagnosis of primary tumors and lymphatic metastases is still hindered by low imaging resolution and poor photostability of fluorescent probes. Herein, we report three novel IR820-fatty acid (FA) conjugates (IR-OA, IR-LA, and IR-PA) for precise lymphatic metastasis illumination and primary tumor diagnosis. The IR-FA conjugates are able to non-covalently bound to albumin in vivo, and the fluorescence quantum yield is significantly enhanced after incubation with bovine serum albumin (BSA) in vitro. Moreover, the BSA-IR-FA conjugates display large Stokes shift (> 120 nm), dramatically improving in vivo imaging resolution. Among them, IR-PA demonstrates distinct advantage over IR-OA, IR-LA, and IR-maleimide (MAL) (fluorescent probe previously reported by our group) in terms of fluorescence quantum yield, photostability, and imaging resolution. As a result, IR-PA exhibits satisfactory imaging results with high fluorescence intensity and imaging resolution in sentinel lymph node metastasis illumination and primary tumor location. Our findings provide a self-adaptive albumin-binding near-infrared probe conjugate for accurate diagnosis of primary tumors and lymphatic metastases.