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Tumor-targeting polypeptide probe and application of probe

A tumor and probe technology, applied in the field of medical imaging, can solve the problems of late pancreatic cancer patients and lost opportunities for surgery, and achieve the effects of small antigenicity, visualization, and stable structure

Active Publication Date: 2021-08-06
中国医科大学
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, most patients with pancreatic cancer lose the chance of surgery due to the late stage of the disease

Method used

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  • Tumor-targeting polypeptide probe and application of probe
  • Tumor-targeting polypeptide probe and application of probe
  • Tumor-targeting polypeptide probe and application of probe

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1 Cy7-YW7, a polypeptide probe targeting pancreatic cancer.

[0036] The polypeptide probe targeting pancreatic cancer provided by the present invention, taking Cy7-YW7 as an example, consists of the polypeptide YW7 (YWRGVYN) reported in the previous patent 201910766853.9 and the near-infrared fluorescent dye Cy7, through PEG3 For coupling, Sangon Bioengineering (Shanghai) Co., Ltd. was commissioned to synthesize fluorescent peptide probes with a purity of 95%. The structural formula and mass spectrometry characterization of Cy7-YW7 are as follows Figure 3-4 shown.

Embodiment 2

[0037] Example 2 In vivo targeted mouse pancreatic cancer ectopic tumor-bearing model experiment.

[0038] Firstly, a pancreatic cancer subcutaneous tumor mouse model was constructed, and the PANC-1 cells in the logarithmic growth phase were digested with trypsin, and the cell concentration was adjusted to 1×10 8 / mL, inoculated subcutaneously into the right dorsal side of nude mice near the armpit, raised in SPF grade after inoculation, and observed the tumor size regularly until the tumor size was about 100mm 3 At the same time, tumor-bearing nude mice with no necrosis and regular tumor shape were screened out and tested in groups. Dissolve Cy7 and Cy7-YW7 in normal saline at a dose of 8 nmol, inject them into the animal model of tumor-bearing nude mice through the tail vein, and detect them at time points of 0, 1, 1.5, 2, 2.5, and 4 hours with a small animal live imager The fluorescence distribution of the tumor, where the imaging images of the control group and the experi...

Embodiment 3

[0040] Example 3 An animal model of subcutaneous tumor of U-87 MG cells was constructed.

[0041] Construction of U-87 MG cell subcutaneous tumor animal model: In vivo animal experiments, glioma U-87 MG cells were transfected with luciferase gene. Amplify transfected glioma U87 cells with 2×10 8 / mL density subcutaneously inoculated to the right dorsal axillary of nude mice at 5-6 weeks, and the status and tumor size of the nude mice were regularly observed. When the tumor volume was about 100mm 3 When , the tumor-bearing nude mice with no necrosis and regular tumor shape were selected for the experiment.

[0042] 8 nmol of Cy7 and Cy7-labeled polypeptide (Cy7-YW7) were injected into the ectopic tumor-bearing nude mice with glioma U-87 MG cells through the tail vein, and imaged by small animals after 0, 1, 2, and 2.5 hours, respectively It was found that Cy7-YW7 specifically aggregated at the tumor site, while the significant accumulation at the tumor site of Cy7 in the cont...

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Abstract

The invention belongs to the technical field of medical imaging, and specifically relates to a tumor-targeting polypeptide probe and application of the probe in tumor imaging. The invention relates to the tumor-targeting polypeptide probe. The general formula of the polypeptide probe is R-X-YW7, the YW7 is a polypeptide specifically targeting ANXA2 in vivo, and the sequence is YWRGVYN; and X is a linker, R is a signal unit, and X and R are covalently connected. The polypeptide probe is applied to preparation of a tumor diagnosis reagent, a tumor imaging reagent, a tumor operation guiding agent and / or a tumor active targeted therapy related drug tracer. Experiments prove that the tumor-targeting polypeptide probe provided by the invention has strong specificity and high sensitivity, and through a nude mouse subcutaneous pancreatic cancer model, a nude mouse subcutaneous glioma model and a nude mouse in-situ glioma model which are cultured in sequence, the polypeptide probe can be specifically absorbed by glioma, and quickly accumulates in tumor cells or tumor tissues within 2 hours; and compared with a control group, the tumor-targeting polypeptide has a remarkable tumor targeting advantage, and is clinically used for tumor diagnosis and treatment.

Description

technical field [0001] The invention belongs to the technical field of medical imaging, and in particular relates to a tumor-targeting polypeptide probe and its application in tumor imaging. Background technique [0002] Cancer is one of the leading causes of death in the world. Its morbidity and mortality are high, diagnosis and treatment are difficult, and it is prone to recurrence and metastasis. In 2018 alone, about 609,640 people died of cancer in the United States, which is equivalent to nearly 1,700 deaths every day. Over the past few decades, significant advances have been made in the treatment of cancer. Conventional methods including surgery, chemotherapy and radiotherapy have greatly improved the survival rate of cancer patients. However, relapse and multidrug resistance remain insurmountable obstacles limiting successful eradication and long-term treatment of cancer. Annexin A2 is a member of the vertebrate annexin family. It is often expressed abnormally hig...

Claims

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Application Information

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IPC IPC(8): A61K49/00G01N21/64
CPCA61K49/0056A61K49/0032A61K49/0054G01N21/6428G01N2021/6432
Inventor 魏敏杰马赫遥雷雨洪宇涵姚维范姜凯
Owner 中国医科大学
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