Preclinical Evaluation of Rationally Designed Peptide-NIRF Probe for c-Met Positive Liver Cancer Imaging-Guided Surgery

Hepatocellular carcinoma (HCC) poses a significant threat to global health, with postoperative survival often compromised by high recurrence rates due to undetectable occult metastases, thereby highlighting the urgent need for early diagnosis and precise intraoperative guidance. The cellular-mesenchymal epithelial transition factor (c-Met), a transmembrane receptor overexpressed in numerous malignancies including HCC, represents a compelling biomarker for cancer diagnosis and therapy. Herein, we reported a near-infrared fluorescence (NIRF) probe, GM-7-MPA, constructed by conjugating a specifically screened high-affinity peptide ligand (GM-7) with a hydrophilic fluorescent dye (MPA). The GM-7-MPA demonstrated high specificity and strong binding affinity for c-Met positive HCC cells in vitro, outperforming GE-137-MPA, which has been clinically evaluated for the detection of colorectal polyps. Furthermore, across various tumor-bearing mouse models, including subcutaneous xenograft, orthotopic liver cancer, and HCC pulmonary metastasis models, GM-7-MPA clearly visualized tumor lesions with a high tumor-to-background ratio (TBR). Critically, in fluorescence-guided surgical navigation studies, the probe accurately delineated tumor margins from adjacent normal tissues and effectively identified residual microfoci, thereby facilitating the complete resection of malignant tumors in xenograft models and orthotopic settings. These findings identified that GM-7-MPA was a promising candidate for the diagnosis and surgical navigation of c-Met positive HCC, demonstrating significant translational potential and clinical application prospects.