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Tumor targeting polypeptides and application thereof

A targeting peptide, targeting technology, applied in tumor targeting peptide and its application field, can solve the problems of differential diagnosis, systemic staging and insufficient early efficacy evaluation

Active Publication Date: 2020-08-21
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For tumors, conventional imaging diagnostic techniques are mainly B-ultrasound, CT and MRI. These imaging diagnostic techniques achieve diagnostic results by displaying tissue function changes and have good application value. There are still some deficiencies in the evaluation

Method used

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  • Tumor targeting polypeptides and application thereof
  • Tumor targeting polypeptides and application thereof
  • Tumor targeting polypeptides and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0088] Fluorescent compound MPA-PEG prepared in embodiment 1 4 - Fluorescence imaging of YQGA-1 in liver cancer HepG2 tumor-bearing mice

[0089] Weigh the PEG solid-phase synthesized by Hangzhou Gutuo Biotechnology Co., Ltd. 4 - YQGA-1 compound 10mg, the prepared dye MPA pure 12.38mg was added to 200μL dimethyl sulfoxide (DMSO), and then 2.3mg 1-(3-dimethylaminopropyl)-3-ethylcarbodi Imine hydrochloride (EDCI) coupling agent and 3.82mg N-hydroxysuccinimide (NHS), after mixing, add 4.1mg N,N-diisopropylethylamine (DIPEA), react overnight at room temperature After the reaction is completed, the preparative liquid phase is used for separation and purification. The preparative liquid phase conditions are as follows: Agilent 1220Infinity II series HPLC system is equipped with an Agilent ZORBAX SB-C18 semi-preparative column (9.4×250mm, 5um), gradient elution for 60 minutes , a flow rate of 2 mL / min, wherein mobile phase A is ultrapure water (0.01% TFA), and B is acetonitrile (0....

Embodiment 2

[0090] The radioactive compound that embodiment 2 prepares 99m Tc-HYNIC-PEG 4 -SPECT-CT imaging of YQGA-1 in liver cancer HepG2 tumor-bearing mice

[0091] 1) Bifunctional chelating agent HYNIC-PEG 4 -Synthesis of NHS

[0092] Add 1g of 6-chloronicotinic acid and 2.0mL of 80% hydrazine hydrate to 10mL of ethanol, and heat to reflux for 4 hours. After the reaction is completed, the solvent is evaporated under reduced pressure, and the obtained viscous material is added to distilled water, and the pH is adjusted to about 5.5 , a solid was precipitated, and 0.86 g of a yellow solid was obtained by suction filtration and drying. The product was determined to be 6-hydrazine nicotinic acid by ESI-MS mass spectrometry and hydrogen nuclear magnetic spectrum. The obtained 0.86g 6-hydrazine nicotinic acid and 0.61g p-aminobenzaldehyde were added to 3.0mL dimethyl sulfoxide (DMSO), and heated for 5-6 hours. After the reaction was completed, they were added to water to precipitate, suc...

Embodiment 3

[0097] The radioactive compound that embodiment 3 prepares 99m Tc-HYNIC-PEG 4 - SPECT-CT imaging of YQGA-1 in glioma U87MG tumor-bearing mice

[0098] The radioactive compound that embodiment 2 prepares 99m Tc-HYNIC-PEG 4 -YQGA-1 and prepared into physiological saline solution (3mCi / mL), 0.1mL (about 300μCi) was injected into three glioma U87MG tumor-bearing nude mice respectively, and 0.5h, 1h, 2h and 2h after administration. 4h for SPECT-CT signal acquisition. Observe the distribution of the probe in the mouse and the enrichment in the tumor area. 1hSPECT-CT imaging results are as follows: figure 2 As shown in B, it can be seen from the figure that the probe can target and recognize glioma U87MG.

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Abstract

The invention discloses tumor targeting polypeptides and application thereof. A series of high-affinity polypeptides can be specifically combined with various tumor cells, and can be used for opticalimaging and nuclear medicine imaging of malignant tumors by utilizing the high-affinity characteristic. High-affinity polypeptide coupled fluorescent dyes can be used as tumor specific targeting molecular probes, are expected to achieve the effect of accurately positioning the tumor boundary, can bring real-time performance for preoperative and intraoperative image navigation, and have the advantage of improving the operation accuracy. The series of polypeptides can also be coupled with radionuclide to detect malignant tumors in vivo in real time so as to achieve the purpose of disease diagnosis or treatment.

Description

technical field [0001] The invention belongs to the technical field of bioengineering pharmaceuticals and the fields of protein polypeptide drugs and biomedical engineering, and specifically relates to tumor-targeting polypeptides and applications thereof. Background technique [0002] Tumor has become the chief culprit threatening human health and life. Therefore, the early diagnosis of tumor and the effective treatment of tumor are particularly important and urgent. For tumors, conventional imaging diagnostic techniques are mainly B-ultrasound, CT and MRI. These imaging diagnostic techniques achieve diagnostic results by displaying tissue function changes and have good application value. There are still some deficiencies in the evaluation. It is undeniable that screening and optimizing tumor-targeting peptides is a new way to develop new molecular imaging drugs for tumor diagnosis, staging, and surgical guidance, and to find smaller lesions and achieve early diagnosis. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/00A61K51/08C07K7/06C07K5/113C07K1/107A61K103/10
CPCA61K49/0056A61K51/08C07K7/06
Inventor 顾月清涂远彪刘培飞王芳
Owner CHINA PHARM UNIV
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