Department of Cardiothoracic Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, China.
Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, China.
Molecules. 2022 Nov 6;27(21):7609. doi: 10.3390/molecules27217609.
Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies globally. Peptide-based tumor-targeted imaging is critical for ESCC imaging. In this study, we aim to identify a peptide-targeting IGF2BP2 that specifically binds to human ESCC for near-infrared imaging of esophageal cancer. Applying phage display techniques, we identified a peptide target for IGF2BP2 which was confirmed to be highly expressed in ESCC cell lines or tumor tissue and may serve as an imaging target for ESCC. We conjugated the peptide to the NIRF group, Cy5, and further evaluated the targeting efficacy of the probe at a cellular level and in animal tumor models. The Cy5 conjugated peptide (P12-Cy5) showed a high binding affinity to human ESCC cells in vitro. In vivo, optical imaging also validated the tumor-targeting ability of P12-Cy5 in KYSE-30-bearing subcutaneous ESCC tumor models. Furthermore, the results of biodistribution showed a significantly higher fluorescence intensity in tumors compared to scrambled peptide, which is consistent with in vivo observations. In summary, an IGF2BP2-targeted peptide was successfully identified. In vitro and in vivo experiments confirmed that P12-Cy5 has high affinity, specificity and tumor-targeting properties. Thus, P12-Cy5 is a prospective NIR probe for the imaging of ESCC.
食管鳞状细胞癌(ESCC)是全球最致命的恶性肿瘤之一。基于肽的肿瘤靶向成像对于 ESCC 成像至关重要。在本研究中,我们旨在鉴定一种针对 IGF2BP2 的肽靶向物,该靶向物特异性结合人 ESCC,用于食管癌的近红外成像。应用噬菌体展示技术,我们鉴定了一种针对 IGF2BP2 的肽靶标,该靶标在 ESCC 细胞系或肿瘤组织中高度表达,可能作为 ESCC 的成像靶标。我们将该肽与近红外荧光团 Cy5 缀合,并进一步在细胞水平和动物肿瘤模型中评估探针的靶向效力。Cy5 缀合的肽(P12-Cy5)在体外对人 ESCC 细胞表现出高结合亲和力。在体内,光学成像也验证了 P12-Cy5 在 KYSE-30 荷瘤皮下 ESCC 肿瘤模型中的肿瘤靶向能力。此外,生物分布结果显示,与 scrambled 肽相比,肿瘤中的荧光强度明显更高,这与体内观察结果一致。总之,成功鉴定了一种针对 IGF2BP2 的肽。体外和体内实验证实,P12-Cy5 具有高亲和力、特异性和肿瘤靶向性。因此,P12-Cy5 是一种有前途的 ESCC 成像近红外探针。