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Purpose <p>Early diagnosis and complete resection of cancer are pivotal for enhancing patient survival rates and prognosis. However, a significant current challenge lies in the lack of specific imaging probes for the identifying various tumor types. The expression levels of neuropilin-1 (NRP1) and glucose transporter 1 (GLUT1) in most tumors, including breast cancer, are closely linked to tumor proliferation and metastasis. This study seeks to develop a novel near-infrared fluorescence (NIRF) probe aimed at precise tumor detection by targeting NRP1 and GLUT1.</p> Procedures <p>G<sub>0</sub> was conjugated with N<sub>3</sub>-PEG<sub>4</sub>-ALKADK and 2-Azido-2-deoxy-D-glucose to synthesize the NGF probe. The spectral properties (fluorescence and absorbance spectra) of NGF were studied in both methanol and water. The targeting specificity of NGF towards NRP1 and GLUT1 was evaluated using confocal fluorescence microscopy imaging, flow cytometry assays and in vivo IVIS spectrum imaging.</p> Results <p>A dual-targeting fluorescent probe named NGF was successfully synthesized to bind to both NRP1 and GLUT1 receptors. NGF exhibited greater hydrophilicity (Log <i>P</i> = -0.95 ± 0.07) and superior optical properties compared to its precursor, G<sub>0</sub>. Confocal fluorescence imaging, flow cytometry assays, and blocking studies revealed that the cellular uptake of NGF correlated with the NRP1 and GLUT1 expression levels across cell lines. Moreover, a strong linear relationship (R<sup>2</sup> = 0.98) was observed between fluorescence intensity and increasing NGF concentrations in MDA-MB-231 cells. In vivo IVIS imaging in animal models demonstrated specific binding of NGF to breast cancer (MDA-MB-231) and colorectal cancer (HCT116), with prolonged retention observed up to 72&#xa0;h.</p> Conclusions <p>This study highlighted the efficient targeting and sustained retention of the dual-target heterodimeric fluorescent probe NGF, binding to NRP1 and GLUT1 receptors. These findings suggest significant potential for clinical applications in early cancer detection and fluorescence image-guided surgery.</p>

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Dual Targeting of Neuropilin-1 and Glucose Transporter for Efficient Fluorescence Imaging of Cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月6日

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  • Jianwei Zhu,
  • Can Zhou,
  • Jian Yang,
  • Zhenhua Wang

摘要

Purpose

Early diagnosis and complete resection of cancer are pivotal for enhancing patient survival rates and prognosis. However, a significant current challenge lies in the lack of specific imaging probes for the identifying various tumor types. The expression levels of neuropilin-1 (NRP1) and glucose transporter 1 (GLUT1) in most tumors, including breast cancer, are closely linked to tumor proliferation and metastasis. This study seeks to develop a novel near-infrared fluorescence (NIRF) probe aimed at precise tumor detection by targeting NRP1 and GLUT1.

Procedures

G0 was conjugated with N3-PEG4-ALKADK and 2-Azido-2-deoxy-D-glucose to synthesize the NGF probe. The spectral properties (fluorescence and absorbance spectra) of NGF were studied in both methanol and water. The targeting specificity of NGF towards NRP1 and GLUT1 was evaluated using confocal fluorescence microscopy imaging, flow cytometry assays and in vivo IVIS spectrum imaging.

Results

A dual-targeting fluorescent probe named NGF was successfully synthesized to bind to both NRP1 and GLUT1 receptors. NGF exhibited greater hydrophilicity (Log P = -0.95 ± 0.07) and superior optical properties compared to its precursor, G0. Confocal fluorescence imaging, flow cytometry assays, and blocking studies revealed that the cellular uptake of NGF correlated with the NRP1 and GLUT1 expression levels across cell lines. Moreover, a strong linear relationship (R2 = 0.98) was observed between fluorescence intensity and increasing NGF concentrations in MDA-MB-231 cells. In vivo IVIS imaging in animal models demonstrated specific binding of NGF to breast cancer (MDA-MB-231) and colorectal cancer (HCT116), with prolonged retention observed up to 72 h.

Conclusions

This study highlighted the efficient targeting and sustained retention of the dual-target heterodimeric fluorescent probe NGF, binding to NRP1 and GLUT1 receptors. These findings suggest significant potential for clinical applications in early cancer detection and fluorescence image-guided surgery.