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Folate-Polyethylene Glycol Conjugated Near-Infrared Fluorescence Probe with High Targeting Affinity and Sensitivity for In Vivo Early Tumor Diagnosis

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Abstract

Purpose

The purpose of this study is to synthesize a folate-polyethylene glycol (PEG) conjugated near-infrared fluorescence probe (fPI-01) for diagnosis of folate receptor (FR)-overexpressed tumors with high sensitivity and specificity.

Procedures

fPI-01 was synthesized, purified, and characterized. Its cytotoxicity and affinity to tumor cells were determined in vitro. The dynamics and biodistribution of the probe was monitored in normal nude mice. And the tumor-targeting capability was investigated in nude mice bearing different tumor xenograft.

Results

fPI-01 was successfully synthesized with strengthened optical properties. Cells experiments showed the probe had high FR affinity and without apparent cytotoxicity. Animal experiments indicated the probe excreted through urine by kidney. And its tumor-targeting ability was demonstrated on different tumor-bearing mice, with high sensitivity and tumor-to-normal tissue contrast ratio (10:1).

Conclusions

fPI-01 is a promising optical agent for diagnosis of FR-positive tumors, especially in their early stage.

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Abbreviations

FR:

folate receptor

PEG:

polyethylene glycol

DCC:

1-(3-dimethylaminopropyl)-3-ethylcarboiimide

NHS:

N-hydroxysuccinimide

TLC:

thin layer chromatography

MTT:

3-(4,5-dimethylthialzol-2-yl)-2,5-diphenyl tetrazolium bromide

CCD:

charge-coupled device

NIR:

near infrared

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Acknowledgments

This research was supported by the Natural Science Foundation Committee of China (NSFC30371362, 30672015, 30700779, 30800257, 30970776) and the major project from the Ministry of Science and Technology for new drug development (2009ZX09310-004).

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    Fei Liu, Dawei Deng, Xinyang Chen & Yueqing Gu

  2. Department of Biomedical Engineering, School of Automation, Nanjing University of Aeronautics and Astronautics, Nanjing, 210016, People’s Republic of China

    Zhiyu Qian

  3. Department of Radiology, School of Medicine, Washington University, St. Louis, MO, USA

    Samuel Achilefu

Authors
  1. Fei Liu
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  2. Dawei Deng
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  3. Xinyang Chen
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  4. Zhiyu Qian
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  5. Samuel Achilefu
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  6. Yueqing Gu
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Corresponding author

Correspondence to Yueqing Gu.

Additional information

Its significance: A folate receptor-targeted near-infrared fluorescence probe (folate-PEG-ICG-Der-01 probe, fPI-01) was synthesized with strengthened fluorescence intensity and photostability. The satisfactory targeting capability for folate receptor-overexpressed tumors was demonstrated in different tumor-bearing mice. The PEG4000 conjugation did improve the dynamics of the probe in mice subjects and enhance the targeting capability and sensitivity to FR-overexpressed tumors. Results in our study indicated the probe possesses great potential in the diagnosis of early stage tumors.

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Liu, F., Deng, D., Chen, X. et al. Folate-Polyethylene Glycol Conjugated Near-Infrared Fluorescence Probe with High Targeting Affinity and Sensitivity for In Vivo Early Tumor Diagnosis. Mol Imaging Biol 12, 595–607 (2010). https://doi.org/10.1007/s11307-010-0305-1

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