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Identification of an IGF2BP2-Targeted Peptide for Near-Infrared Imaging of Esophageal Squamous Cell Carcinoma
Wenbin Shu1, Yitai Xiao2, Lizhu Wang3
1Department of Cardiothoracic Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, China.
Abstract:
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.
Insights
Researchers identified a novel peptide targeting Insulin-like Growth Factor 2 mRNA-Binding Protein 2 (IGF2BP2) for esophageal squamous cell carcinoma (ESCC) imaging. This peptide, conjugated to a near-infrared dye, shows high specificity and tumor-targeting capabilities for improved esophageal cancer detection.
Area of Science:
- Oncology
- Biotechnology
- Medical Imaging
Background:
- Esophageal squamous cell carcinoma (ESCC) is a globally lethal malignancy.
- Effective imaging strategies are crucial for early detection and treatment of ESCC.
- Peptide-based tumor-targeted imaging offers a promising approach for enhanced specificity.
Purpose of the Study:
- To identify and characterize a peptide that specifically targets Insulin-like Growth Factor 2 mRNA-Binding Protein 2 (IGF2BP2) in human ESCC.
- To develop a near-infrared (NIR) fluorescent probe for in vitro and in vivo imaging of ESCC.
- To evaluate the tumor-targeting efficacy and specificity of the developed probe.
Main Methods:
- Phage display techniques were employed to identify peptides targeting IGF2BP2.
- The identified peptide was conjugated to a near-infrared fluorescent dye (Cy5) to create the P12-Cy5 probe.
- In vitro binding assays using ESCC cell lines and in vivo optical imaging in mouse models were performed to assess targeting efficacy.
Main Results:
- A peptide with high binding affinity to IGF2BP2, which is overexpressed in ESCC, was successfully identified.
- The P12-Cy5 probe demonstrated specific binding to human ESCC cells in vitro.
- In vivo studies confirmed the tumor-targeting ability of P12-Cy5 in a subcutaneous ESCC xenograft model, with significant fluorescence accumulation in tumors.
Conclusions:
- An IGF2BP2-targeted peptide probe (P12-Cy5) was developed for near-infrared imaging of ESCC.
- P12-Cy5 exhibits high affinity, specificity, and effective tumor-targeting properties.
- This probe holds potential as a valuable tool for the diagnostic imaging of esophageal squamous cell carcinoma.
