Tumor killing polypeptide capable of being self-assembled into hydrogel and application thereof

Abstract

The invention relates to a tumor killing polypeptide capable of being self-assembled into a hydrogel, wherein the tumor killing polypeptide includes a C-end self-assembly structural domain and an N-end killing structural domain; the self-assembly structural domain and the killing structural domain are connected by a flexible structural domain; the self-assembly structural domain has a sequence of (RADA)7-9. The tumor killing polypeptide capable of being self-assembled into hydrogel does not affect the hydrogel self-assembling function and also has the ability to kill tumor. Through repeated multi-time local injection, slow release agents are directly implanted into tumor bodies, peritumoral parts or postoperative residual cavities, open surgery is not required to be carried out so as to prevent exposure of the tumor, infection, bleeding and other complications are reduced, and body and economic burden of patients are reduced. The self-assemble polypeptide material can be loaded with chemotherapeutic drugs for directly killing the tumor, and also can be loaded with tumor antigen proteins, tumor lysates or tumor RNA as a tumor nano vaccine for use.

Description

technical field [0001] The invention relates to the field of anti-tumor, more particularly, relates to a tumor-killing polypeptide that can self-assemble into a hydrogel. Background technique [0002] Solid tumors (such as brain glioma, liver cancer, soft tissue sarcoma, etc.) are common primary malignant tumors in clinical practice. Most solid tumors show invasive and expansive growth, so surgery is not easy to remove. At present, the treatment of this kind of malignant tumor is still a recognized problem in the world. The most commonly used clinical treatment methods mainly include surgery, chemotherapy, radiotherapy and comprehensive treatment, but none of them have achieved satisfactory results. There are two main problems: ①The boundary between tumor tissue and normal brain tissue is not clear, so it is difficult to perform a true surgical resection and precise radiotherapy, and the residual tumor tissue becomes the source of local recurrence; ②Chemotherapy drugs requir...

AI Technical Summary

Problems solved by technology

At present, RADA-16 is one of the most commonly used self-assembled polypeptide materials. Functional peptide fragments (such as IKVAV) are connected to RADA-16 molecules through solid-phase synthesis. After self-assembly of polypeptide molecules, the gel material can have the same functions as Peptide fragments have the same biological activity, but have the following disadvantages: 1) It has no anti-tumor activity; 2) RADA-16 can form a gel, but if the amino acid sequence of the functional peptide fragment carried is too long (such as melittin: GIGAVLKVLTTGLPALISWIKRKRQQ), the functional peptide fragment will disrupt the spontaneous aggregation of RADA-16 to form a Beta sheet structure, and cannot self-assemble into a gel

However, the instability of ICG in aqueous solution and its rapid clearance in the body limit its application.

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