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Synthesis of a novel specific nectin-4 tumor-targeted peptide optical molecular probe and its preliminary study in
Ting Jiang1, Ke Dong1, Jianfei Fu2
1Department of Nuclear Medicine, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, Zhejiang, China.
Abstract:
Nectin-4/PVRL-4 is overexpressed in tumors, driving proliferation and invasion. It's a key target for solid tumor therapy. Current tumor imaging methods are inadequate. Studying nectin-4 in lung cancer helps identify diagnostic biomarkers and develop radionuclide probes, intraoperative visualization,and new chemotherapies. High nectin-4 expression in lung cancer tissues was confirmed using TCGA data and IHC. Three optical probes targeting nectin-4 were synthesized. Optimal binding conditions were explored, and binding rates were assessed. Animal experiments showed the probes' specificity and biodistribution. The probes effectively targeted nectin-4, with Cy5.5-nectin-4 PEP 02 showing the highest binding rate. In vivo, the probe targeted lung cancer tissues, indicating potential for intraoperative navigation. Nectin-4 is a promising target for lung cancer and intraoperative navigation, guiding further research.
Insights
Nectin-4 (PVRL-4) is overexpressed in lung cancer, driving tumor growth. New optical probes targeting nectin-4 show promise for improved cancer imaging and intraoperative navigation.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Nectin-4 (PVRL-4) is a cell adhesion molecule implicated in tumor progression and invasion.
- Overexpression of Nectin-4 is observed in various solid tumors, making it a significant therapeutic target.
- Current diagnostic and imaging techniques for solid tumors, particularly lung cancer, have limitations.
Purpose of the Study:
- To investigate the role of Nectin-4 in lung cancer.
- To develop and evaluate novel optical probes for Nectin-4 detection.
- To assess the potential of Nectin-4 as a target for diagnostic imaging and intraoperative navigation in lung cancer.
Main Methods:
- Nectin-4 expression analysis in lung cancer tissues using TCGA data and immunohistochemistry (IHC).
- Synthesis of three Nectin-4-targeting optical probes.
- In vitro assessment of probe binding kinetics and specificity.
- In vivo biodistribution and targeting studies in animal models.
Main Results:
- High Nectin-4 expression was confirmed in lung cancer tissues.
- Three optical probes were successfully synthesized and characterized.
- The probe Cy5.5-nectin-4 PEP 02 demonstrated the highest binding affinity and specificity for Nectin-4.
- In vivo studies confirmed effective targeting of lung cancer tissues by the developed probes.
Conclusions:
- Nectin-4 is a validated and promising molecular target in lung cancer.
- The developed optical probes show significant potential for Nectin-4-targeted tumor imaging.
- These probes could facilitate intraoperative navigation and improve lung cancer management.
