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作者:

Mo, Shanyan (Mo, Shanyan.) | Zhang, Xiaoting (Zhang, Xiaoting.) | Hameed, Sadaf (Hameed, Sadaf.) | Zhou, Yiming (Zhou, Yiming.) | Dai, Zhifei (Dai, Zhifei.)

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摘要:

Near-infrared (NIR) fluorescence imaging has been proved as an effective modality in identifying the tumor border and distinguishing the tumor cells from healthy tissue during the oncological surgery. Developing NIR fluorescent probes with high tumor to background (T/B) signal is essential for the complete debulking of the tumor, which will prolong the survival rate of tumor patients. However, the nonspecific binding and "always-on" properties of the conventional fluorescent probes leads to high background signals and poor specificity. Method: To address this problem, glutathione (GSH)-responsive, two disulfide-bonded dicyanine dyes (ss-diCy5 and ss-diNH800CW) were synthesized. As synthesized dyes are quenched under normal physiological conditions, however, once reached to the tumor site, these dyes are capable of emitting strong fluorescence signals primarily because of the cleavage of the disulfide bond in the tumor microenvironment with high GSH concentration. Besides, the GSH-responsive behavior of these dyes was monitored using the UV-vis and fluorescence spectroscopy. The diagnostic accuracy of the aforementioned dyes was also tested both in tumor cells and 4T1-bearing mice. Results: The fluorescence signal intensity of disulfide dicyanine dyes was quenched up to 89% compared to the mono cyanine dyes, thus providing a very low fluorescence background. However, when the disulfide dicyanine dye reaches the tumor site, the dicyanine is cleaved by GSH into two mono-dyes with high fluorescence strength, thus producing strong fluorescent signals upon excitation. The fluorescent signal of the dicyanine was enhanced by up to 27-fold after interacting with the GSH solution. In vivo xenografts tumor studies further revealed that the fluorescence signals of aforementioned dyes can be quickly recovered in the solid tumor. Conclusion: In summary, the disulfide dicyanines dyes can provide a promising platform for specific tumor-activatable fluorescence imaging with improved T/B value.

关键词:

Fluorescence imaging molecular probe tumor response disulfide dicyanine fluorescence quenching

作者机构:

  • [ 1 ] [Mo, Shanyan]Peking Univ, Dept Biomed Engn, Coll Engn, Beijing 100871, Peoples R China
  • [ 2 ] [Zhang, Xiaoting]Peking Univ, Dept Biomed Engn, Coll Engn, Beijing 100871, Peoples R China
  • [ 3 ] [Hameed, Sadaf]Peking Univ, Dept Biomed Engn, Coll Engn, Beijing 100871, Peoples R China
  • [ 4 ] [Zhou, Yiming]Peking Univ, Dept Biomed Engn, Coll Engn, Beijing 100871, Peoples R China
  • [ 5 ] [Dai, Zhifei]Peking Univ, Dept Biomed Engn, Coll Engn, Beijing 100871, Peoples R China
  • [ 6 ] [Mo, Shanyan]Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing 100124, Peoples R China

通讯作者信息:

  • [Dai, Zhifei]Peking Univ, Dept Biomed Engn, Coll Engn, Beijing 100871, Peoples R China

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来源 :

THERANOSTICS

ISSN: 1838-7640

年份: 2020

期: 5

卷: 10

页码: 2130-2140

1 2 . 4 0 0

JCR@2022

ESI学科: CLINICAL MEDICINE;

ESI高被引阀值:126

被引次数:

WoS核心集被引频次: 33

SCOPUS被引频次: 32

ESI高被引论文在榜: 0 展开所有

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