A kind of tumor-killing polypeptide that can self-assemble into hydrogel and its application

Abstract

The invention relates to a tumor-killing polypeptide capable of self-assembling into a hydrogel, which includes a C-terminal self-assembly domain and an N-terminal killing domain, and the self-assembling domain and the killing domain are connected by a flexible domain , the sequence of the self-assembly domain is (RADA) 7‑9 . The tumor-killing polypeptide that can self-assemble into a hydrogel neither affects its self-assembly into a hydrogel function, but also has the ability to kill tumors. The slow-release agent can be directly implanted into the tumor body, tumor side or postoperative residual cavity through repeated local injections, without open surgery to expose the tumor, reduce infection, bleeding and other complications, and reduce the physical and economic burden of patients. Self-assembled polypeptide materials can be loaded with chemotherapy drugs to directly kill tumors, and can also be loaded with tumor antigen proteins, tumor lysates or tumor RNA as tumor nano-vaccine.

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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