Tumor-specific targeting polypeptide and application thereof

A tumor-specific, targeting peptide technology, applied to phage-displayed peptides and their application fields, can solve the problems of uncontrollable late-stage metastasis, lack of tumor cell specificity, and reduced drug efficacy, and achieve good tumor targeting effect, Sensitive and penetrating effect of tumor diagnosis

Active Publication Date: 2014-09-03
THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Both surgery and radiotherapy are local treatments, which cannot control advanced metastasis, and many patients cannot receive this type of treatment due to their weak constitution; while chemotherapy has some chemotherapeutic drugs with good curative effect, but due to the lack of tumor cell specificity, While killing tumor cells, it also kills a large number of bone marrow and other vigorously proliferating cells, all of which have strong side effects, and drug resistance often occurs after repeated chemotherapy, greatly reducing the efficacy of drugs

Method used

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  • Tumor-specific targeting polypeptide and application thereof
  • Tumor-specific targeting polypeptide and application thereof
  • Tumor-specific targeting polypeptide and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0088] Example 1, the in vivo anti-tumor effect of the linear heptapeptide whose sequence is LPLTPLP combined with anti-tumor drugs

[0089] In this example, the targeting peptide is connected with the drug-loaded nano-preparation to construct the targeted nano-preparation.

[0090] Preparation of Targeted Nanoformulations

[0091] The drug-loaded nanoparticles containing docetaxel were resuspended in MES buffer solution, a coupling condensing agent was added, and after incubation at room temperature for 15 minutes, 0.1 mg / ml of targeting peptide was added. The sequence of the targeting peptide was LPLTPLP, Rotate and stir for 2 hours, centrifuge at 15,000 rpm for 10 minutes to collect particles, resuspend and wash three times, and then freeze-dry to obtain the targeted nano-preparation.

[0092] Experimental study of anti-tumor therapy in vivo

[0093] After adapting to the environment, 50 Balb / c nude mice were subcutaneously injected with 106 A549 cells per mouse in the ri...

Embodiment 2

[0099] Example 2, the in vivo anti-tumor effect of the combination of the obtained cyclic peptide with the sequence of NH2-CVKTPAQSC-COOH and anti-tumor drugs

[0100] The sequence obtained in this study is shown as SEQ ID NO: 2, which is NH2-CVKTPAQSC-COOH, where C and C are two cysteines formed by a disulfide bond to form a cyclic peptide.

[0101] Table 2 lists the liver metastases in different groups after administration. The liver metastases were severe in the NDTX group, with an average number of metastatic nodules on the liver surface of 274, while the average number of metastatic nodules on the liver surface in the TNDTX-H group was less than 67.

[0102] Table 2. Statistical table of liver surface metastatic nodules in each group

[0103]

[0104]

[0105] For the analysis of pathological changes at the liver histological level in each group, see Figure 4 , 5 .

[0106] Depend on Figure 4 It can be seen that compared with the normal nude mouse liver (Norm...

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Abstract

The invention relates to a tumor-specific targeting polypeptide and an application thereof. Particularly, the amino acid sequence of the tumor-specific targeting polypeptide is shown in SEQ ID No.2. The polypeptide provided by the invention is connected with a polyamide-amine dendritic high molecular nano material and then can be well combined with various tumor cells in vitro and has a wide application in diagnostic imaging and targeted therapy of tumors as a target agent.

Description

[0001] This application is a divisional application of a Chinese patent application with the application number 201310258476.0, the application date is June 26, 2013, and the invention title is "a tumor-specific targeting polypeptide and its application". technical field [0002] The invention belongs to the technical field of protein polypeptides, and relates to polypeptides displayed by phages and applications thereof. More specifically, it is a polypeptide that can specifically bind to tumor cells and its preparation method and application. Background technique [0003] Tumor is one of the most frequently occurring diseases in the world. In many advanced countries, the mortality rate of lung cancer ranks first among all cancer mortality rates. Currently, lung cancer treatment mainly includes surgery, radiotherapy and chemotherapy. Both surgery and radiotherapy are local treatments, which cannot control advanced metastasis, and many patients cannot receive this type of tr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06C12N15/11A61K47/48A61K31/337A61K49/14A61P35/00A61K47/42
Inventor 左萍萍刘雁勇杨楠姜尧张慧丰
Owner THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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