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cNGR-based synergistic-targeted NIR fluorescent probe for tracing and bioimaging of pancreatic ductal adenocarcinoma

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Abstract

Identification of fluorescent biomarkers with peptide ligand-directed receptors for diagnosis or theranostic of pancreatic ductal adenocarcinoma (PDAC) is still challenging. As potential prognostic/predictive bioimaging targets, both aminopeptidase N (APN, known as CD13) and Caveolin-1 are found as upregulation on the cell membrane surface of PDAC, in which APN is the principal receptor of the cyclic peptide cNGR (Asn-Gly-Arg, NGR) and Caveolin-1 can synergistically mediate endocytosis in this receptor-targeted process. Herein, we conjugate cNGR to dicyanomethylene-4H-pyran (DCM) chromophore to develop a synergistic-targeted near-infrared (NIR) fluorescent probe DCM-cNGR with strongly intrinsic NIR fluorescence, stable optical performance, low cytotoxicity, and rapid accumulation in PANC-1 cells with the synergistic overexpressed APN receptor-targeted and Caveolin-1-mediated endocytosis. As demonstrated, DCM-cNGR can realize noninvasive NIR imaging for targeting PANC-1 tumor in vivo after intravenous injection into PANC-1 xenograft tumor of nude mice, making a great promise to improve the precision diagnosis and therapy of pancreatic cancer with real time tracing and bioimaging of PDAC in vitro and in vivo.

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Acknowledgments

This work was supported by the National Basic Research Program of China (2013CB733700), the National Natural Science Foundation of China for Creative Research Groups (21421004), Key Project (21636002), and Distinguished Young Scholars (21325625), NSFC/China, the Oriental Scholarship, Science and Technology Commission of Shanghai Municipality (15XD1501400), the Fundamental Research Funds for the Central Universities (222201717003), and Program of Introducing Talents of Discipline to Universities (B16017).

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  1. These authors are contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, China

    Yan Tang, Hui Li, Meiying Zeng & Yingsheng Cheng

  2. Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, 200237, China

    Andong Shao, Qiang Li, Ming Liu & Weihong Zhu

  3. Department of Interventional Oncology, Dahua Hospital, Shanghai, 200237, China

    Jun Cao

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  1. Yan Tang
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Correspondence to Yingsheng Cheng or Weihong Zhu.

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Tang, Y., Shao, A., Cao, J. et al. cNGR-based synergistic-targeted NIR fluorescent probe for tracing and bioimaging of pancreatic ductal adenocarcinoma. Sci. China Chem. 61, 184–191 (2018). https://doi.org/10.1007/s11426-017-9092-9

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  • DOI: https://doi.org/10.1007/s11426-017-9092-9

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