Identification of a Glypican‐3‐Binding Peptide for In Vivo Non‐Invasive Human Hepatocellular Carcinoma Detection

Early and accurate detection of hepatocellular carcinoma (HCC) is essential to improve the prognosis of patients and reduce the morbidity of surgical therapy. Glypican‐3 (GPC3) is a protein abnormally expressed in HCC that has been identified as a serological and histochemical HCC marker. A novel peptide that specifically recognizes GPC3 will facilitate early detection of HCC and guide the treatment strategy. Herein, phage display screening technology is utilized to obtain a GPC3 binding peptide (GBP) using HCC cells expressing GPC3 in varying abundances. After seven rounds of panning, a peptide with sequence of THVSPNQGGLPS is identified with 735.2 ± 53.6 × 10−9 m affinity to GPC3. The ability to target GPC3 in vivo is evaluated by intravenous injection of GBP labeled with a near‐infrared dye, Cy5.5, into a HCC tumor‐bearing mouse model. Significant high tumor accumulation (tumor/muscle ratio: 6.49 ± 0.55) of Cy5.5‐GBP in HepG2 tumors is observed compared with that of the low GPC3 expressing prostate cancer cell line, PC3 (tumor/muscle ratio: 1.15 ± 0.32). By targeting GPC3, GBP differentiates tumor tissues from normal liver tissues in patients, suggesting a great clinical translation potency of GBP. Collectively, GBP demonstrates great potential for HCC detection via fluorescent imaging or histological staining. image