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

IF 3 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING Molecular Imaging and Biology Pub Date : 2025-03-06 DOI:10.1007/s11307-025-01993-7

Jianwei Zhu, Can Zhou, Jian Yang, Zhenhua Wang

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引用次数: 0

Abstract

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.

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来源期刊

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.