Nitroreductase-specific fluorescent probe and preparation thereof and application in tumor-targeted fluorescence imaging and monitoring of tumor hypoxia

A fluorescent probe and tumor-targeting technology, applied in the field of biomedicine, can solve the problems of high permeability, increased blood flow viscosity resistance, inability to establish new blood vessel network in time and effectively, and achieve high fluorescence quantum yield , the effect of sensitive detection

Inactive Publication Date: 2017-05-31
EAST CHINA UNIV OF SCI & TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, in the tumor tissue, the uncontrolled growth and proliferation of tumor cells consume a large amount of nutrients and oxygen, and the new blood vessel network cannot be established in a timely and effective manner, or the structure and function of the new blood vessel network are abnormal, and there is a temporary closure or "blind end". ”; and the permeability is high, and the extravasation of fluid into the interstitial space leads to an increase in the viscous resistance of blood flow

Method used

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  • Nitroreductase-specific fluorescent probe and preparation thereof and application in tumor-targeted fluorescence imaging and monitoring of tumor hypoxia
  • Nitroreductase-specific fluorescent probe and preparation thereof and application in tumor-targeted fluorescence imaging and monitoring of tumor hypoxia
  • Nitroreductase-specific fluorescent probe and preparation thereof and application in tumor-targeted fluorescence imaging and monitoring of tumor hypoxia

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Embodiment Construction

[0031] The probe is composed of a detection group and a fluorophore linked by a chemical bond, and is summarized as structure type I, which can be expressed as sensor-dye.

[0032] Specific examples of fluorescent probes specific for nitroreductase are:

[0033] Structure type I: dye-sensor

[0034]

[0035] As the specific substrate of nitroreductase, the type I probe itself is due to the strong electron-withdrawing effect of the nitro group, which leads to the d-PET effect and quenches the molecular fluorescence. When it is reduced by the nitroreductase, the compound ( 1), the fluorescence intensity is greatly enhanced. The activity of nitroreductase in biological samples such as enzymes or cell preparation fluids and cells is determined by quantitatively detecting the amount of reduction products generated per unit time.

[0036] The identification mechanism is as follows:

[0037]

[0038] 1) In common buffers such as PBS or Tris-HCl, the reaction temperature is b...

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Abstract

The invention provides a nitroreductase-specific fluorescent probe and the preparation thereof and a reagent for applying the nitroreductase-specific fluorescent probe to tumor-targeted fluorescence imaging and monitoring of tumor hypoxia. The reagent is connected by tumor biomarker identifying groups (sensor), tumor targeted groups (target) and fluorescent groups (dye) via chemical bonds. The reagent can be used in the tumors with hypoxic microenvironment and high expression of nitroreductase based on tumor hypoxia and the high expression of nitroreductase in hypoxic tumors. Combined with a fluorescence imager, the reagent can be used in tumor targeted fluorescence imaging, tumor hypoxia monitoring and the monitoring of tumor metastasis, etc. The reagent realizes high sensitivity and high specificity in application and provides an effective tool for medical study of cancer and clinical monitoring and treatment of tumor metastasis, thereby having a good application prospect in tumor-targeted fluorescence imaging, tumor hypoxia monitoring and monitoring of tumor metastasis.

Description

technical field [0001] The invention belongs to the field of biomedical technology, and relates to a class of detection reagents and their preparation methods and applications, specifically specific fluorescent probes for nitroreductase and their preparation methods, and are used for tumor-targeted fluorescence imaging and monitoring of tumor hypoxia Applications. Background technique [0002] The growth and proliferation of cells depend on sufficient oxygen and energy supply. In tissues with normal oxygen supply, about 90% of the energy source of cells depends on the aerobic oxidation of mitochondria. However, in the tumor tissue, the uncontrolled growth and proliferation of tumor cells consume a large amount of nutrients and oxygen, and the new blood vessel network cannot be established in a timely and effective manner, or the structure and function of the new blood vessel network are abnormal, and there is a temporary closure or "blind end". "; and the permeability is hi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D311/82C07K7/64A61K49/00
CPCA61K49/0043A61K49/0056C07D311/82C07K7/64
Inventor 吴君臣罗深圳姚德帆李尚张文旭赖燕华朱晓敏田禾
Owner EAST CHINA UNIV OF SCI & TECH
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