Abstract
Tumor-targeting peptides functioned as molecular probes are essential for multi-modality imaging and molecular-targeting therapy in caner theronostics. Here, we performed a phage-displayed bio-panning to identify a specific binding peptide targeting Glypican-3 (GPC-3), a promising biomarker in hepatocellular carcinoma (HCC). After screening in the cyclic peptide library, a candidate peptide named F3, was isolated and showed specific binding to HCC cell lines. In a bio-distribution study, higher accumulation of F3 peptide was observed in HepG-2 tumors compared to PC-3 tumors in xenograft models. After labeling with radioactive 68Ga, the F3 peptide tracer enabled the specific detection of tumors in HCC tumor models with PET imaging. More importantly, the expression of GPC-3 in human tissue samples may be distinguished by an F3 fluorescent peptide probe indicating its potential for clinical application. This cyclic peptide targeting GPC-3 has been validated, and may be an alternative to serve as an imaging probe or a targeting domain in the drug conjugate.
Highlights
Hepatocellular carcinoma (HCC) derived from malignant hepatocytes is among the most common cancers in adults
The foreign cyclic peptide displayed on M13 phage was deduced from the DNA sequences based on triple-code theory
Analysis of the DNA sequencing data revealed that one cyclic peptide containing 7 amino acids restricted in two cystines was present at a high frequency, 42.9% among 93 individuals (Figure 1B), A
Summary
Hepatocellular carcinoma (HCC) derived from malignant hepatocytes is among the most common cancers in adults. Some therapeutic approaches have been explored for HCC treatment, such as liver transplantation, moleculartargeting drugs and immunotherapy These treatments are effective for a portion of patients, the survival rate of HCC is still unfavorable and the majority of patients are diagnosed at late stage of the first visit, suggesting poor prognosis [2,3,4]. For this reason, accurate and precise approaches to early diagnosis of HCC are urgently needed.
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