Based on lapatinib innovative near-infrared fluorescent probes targeting HER1/HER2 for in vivo tumors imaging

Human epidermal growth factor receptors HER1 and HER2, overexpressed in non-small cell lung cancer, colorectal cancer, liver cancer, are key regulators of tumor cells proliferation, invasion and survival. Many antibody- or peptide-based fluorescent probes targeted to HER1/HER2 are under active clinical evaluation. However, the effective small-molecule near-infrared (NIR) fluorescent probes are still lacking. Herein, with the strategy of drug repurposing, we developed a series of HER1/HER2-targeted probes YQ-H (01-07) composed of fluorophore (a cyanine dye, MPA), linker unit and targeted unit (lapatinib, LAP). The synthesized probes were evaluated in vitro and in vivo tumor specificity/affinity. Specially, the probe YQ-H-06 exhibited optimal pharmacokinetic property and tumor/normal tissue ratio (T/N) in tumor-bearing mice. Furthermore, we evaluated the targeting capability of YQ-H-06 in orthotopic colorectal cancer and orthotopic hepatic carcinoma mice. It was indicated that YQ-H-06 had the characteristic of great biosafety, favorable pH and chemical stability, as well as provided excellent tumor contrast in orthotopic murine tumor models. The NIR fluorescent probe YQ-H-06 will shed light on tumor detection and fluorescence-guided surgery.