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Tumor specific target polypeptide and application thereof

A tumor-specific, peptide-targeting technology, which is applied to phage-displayed peptides and its application fields, can solve the problems of lack of tumor cell specificity, uncontrollable late metastasis, and reduced drug efficacy, and achieve sensitive and good tumor diagnosis. Targeting effect, strong penetrating effect

Active Publication Date: 2013-10-09
THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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 target polypeptide and application thereof
  • Tumor specific target polypeptide and application thereof
  • Tumor specific target polypeptide and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0086] Example 1, the in vivo anti-tumor effect of the linear heptapeptide whose sequence is LPLTPLP combined with anti-tumor drugs

[0087] In this example, the targeting peptide is connected with the drug-loaded nano-preparation to construct the targeted nano-preparation.

[0088] Preparation of Targeted Nanoformulations

[0089] 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.

[0090] Experimental study of anti-tumor therapy in vivo

[0091] After adapting to the environment, 50 Balb / c nude mice were subcutaneously injected with 106 A549 cells / mouse in the right ...

Embodiment 2

[0097] 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

[0098] 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.

[0099] 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.

[0100] Table 2. Statistical table of liver surface metastatic nodules in each group

[0101]

[0102] For the analysis of pathological changes at the liver histological level in each group, see Figure 4 , 5 .

[0103] Depend on Figure 4 It can be seen that compared with the liver of normal nude mice (Normal), the ...

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Abstract

The invention relates to a tumor specific target polypeptide and an application thereof. More specifically, the amino acid sequence of the tumor specific target polypeptide provided by the invention is shown by SEQ ID No.1 or 2. After being connected with a polypeptide-amine type dendritic macromolecular nano material, the polypeptide provided by the invention can be perfectly combined with multiple tumor cells in vivo; and as a target agent, the polypeptide has broad application in terms of diagnostic imaging and targeted therapy of tumors.

Description

technical field [0001] 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 [0002] 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 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 ...

Claims

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Application Information

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IPC IPC(8): C07K7/06C12N15/11A61K49/00A61K47/42A61K31/337A61P35/00
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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