11 segment human digestive tract tumoure blood vessel speicfic conjugated cyclopeptide GX series

Abstract

The invention discloses 11 segments of human alimentary canal tumor blood vessel specific binding cyclic peptide series. The present invention utilizes a random phage cyclic 7 peptide library and an immunosuppressed mouse subrenal capsule human metastatic tumor model to successfully screen out a cyclic 7 that can specifically bind to blood vessels of human esophageal squamous cell carcinoma and human gastric poorly differentiated adenocarcinoma Peptides GX1-GX11. Plaque titration of transplanted tumor tissues, immunohistochemical staining of transplanted tumor tissues and human gastric cancer and esophageal cancer tissues, and competition inhibition experiments between GX1 synthetic peptides and GX1-presenting phages in vivo showed that the series of 7 peptides combined with blood vessels in human digestive tract tumor tissues specificity. The uniqueness of these protein sequences was confirmed after sequencing. These polypeptide sequences will have great potential value in the targeted therapy of tumor blood vessels and the development of specific molecular marker reagents for tumor blood vessels.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and relates to in vivo screening of blood vessel-specific binding peptides, in particular to a series of 11-segment human digestive tract tumor blood vessel-specific binding cyclic peptides. Background technique [0002] Although gastric cancer has gradually decreased in recent years, it still ranks third among the top ten causes of cancer death in China. The traditional treatment methods are still surgery, chemotherapy and radiotherapy. In 1971, Professor Folkman proposed the theory that tumor growth and metastasis depend on blood vessels, and blocking tumor angiogenesis became a method to inhibit tumor growth. Compared with traditional methods, tumor vascular inhibition therapy has the following advantages: ① drug resistance is not easy to develop; ② drugs are easy to reach the target site; ③ inhibit tumor metastasis; ④ no genotoxicity; ⑤ strong effect, etc. For exa...

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Problems solved by technology

However, although tumor vascular suppression therapy has obvious advantages, it also has some disadvantages: ① Tumor blood vessels are not well targeted, it is difficult to completely cure the tumor, and there is a potential risk of inhibiting normal endothelial cells

②Low expression efficiency and limited curative effect

③Most of the angiogenesis inhibitory molecules currently entering clinical trials have low expression efficiency in vivo, and cannot maintain therapeutic concentrations locally in tumor blood vessels

[0005] At present, most of the screening methods use in vitro screening, but for tumor vascular endothelial cells, direct isolation and in vitro culture of human tumor vascular endothelial cells, one is the difficulty of separation technology operation, and the other is that long-term in vitro culture makes endothelial cells lose their vitality in vivo. The living environment of endothelial cells loses tissue specificity

Some in vivo experiments mostly use human tumor cell lines or nude mouse models of transplanted tissue tumors, and some use transgenic mice. The growth cycle of transplanted tumors is longer, which often changes the shape and viability of tumor cells. , or loss of human origin, thus affecting the results of such experiments may not be ideal

[0006] The 6-day method established the transplanted tumor model of human gastric cancer or esophageal cancer in CTX immunosuppressed Balb / c mice. Due to the short growth cycle of the transplanted tumor, although the mouse vascular endothelial cells began to bud out and cause recanalization of blood vessels with human gastric cancer tissue, it was guaranteed However, the vascular endothelial cells inside the tumor mass were not completely replaced by mouse vascular endothelial cells within 6 days, and most of them remained human-derived

[0007] Although the sequence of the simulated small peptide screened by the applicant has no similarities with natural known molecules, this does not mean that it does not have similar functions to natural molecules, nor can it be denied that it does not have the ability to combine with natural molecules. ability

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