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Nanometer material based on loaded GSDMD protein N-terminal peptide fragment and application thereof

A technology of GSDMD-N and GSDMD-N-PDPA, applied in the field of biomedicine, can solve the problems of less tumor cell effect, lack of targeting, many side effects, etc., achieve local immune function enhancement, economical preparation cost, and low preparation cost Effect

Pending Publication Date: 2022-06-24
SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The concept of immune enhancer has been around since 1980, but with the development of biological therapy, because of its obvious shortcomings, its clinical popularity is lower than that of chemotherapy, radiotherapy and more potential immunotherapy. T cell therapy and molecular targeted drug therapy
The main reasons for this may be: 1. The lack of targeting of traditional immune enhancers can easily cause the immune promotion reaction of the whole body, resulting in more side effects while exerting anti-tumor effects; In addition to the chemotaxis of innate immune cells to the tumor site, it has less effect on tumor cells and often needs to be combined with other anti-tumor drugs for treatment.

Method used

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  • Nanometer material based on loaded GSDMD protein N-terminal peptide fragment and application thereof
  • Nanometer material based on loaded GSDMD protein N-terminal peptide fragment and application thereof
  • Nanometer material based on loaded GSDMD protein N-terminal peptide fragment and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Example 1 GSDMD-N-terminal plasmid vector design

[0045] Aiming at the characteristics of GSDMD, the present invention designed a plasmid vector ( figure 1 ), and the red fluorescent marker of mcherry was added to the vector. The vector was transfected into tumor cells (MDA-231), and it was found that all cells with red fluorescence (transfected successfully) died, which proved that the plasmid has cytotoxicity and can kill tumor cells. Wherein, the full-length nucleotide sequence of GSDMD is shown in SEQ ID NO: 1, the nucleotide sequence of GSDMD-N-terminal is shown in SEQ ID NO: 2, and the nucleotide sequence of GSDMD-N-terminal plasmid is shown in SEQ ID NO: 3 shown.

[0046] We believe that GSDMD-N has a general killing effect on tumors, and we have verified this in oral tumor cells, breast cancer cells, liver cancer cells, malignant fibroblasts and other cells ( figure 2 ). The results once again proved that GSDMD-N-terminal vector can kill tumor cells in a l...

Embodiment 2

[0047] Example 2 GSDMD-N-terminal plasmid vector has immune cell chemotactic potential

[0048] GSDMD-induced pyroptosis can induce chemotaxis of immune cells in tumors. Therefore, we have reason to speculate that the GSDMD-N-terminal plasmid can promote immune infiltration in tumors. Plasmid transfection and PCR detection of intracellular chemokines were performed on oral cancer cell lines (CAL-27, HSC-6) and breast cancer cells (MDA-231 and MCF-7) ( image 3 ). The results showed that after transfection of GSDMD-N-terminal plasmid, a large number of innate immune cell chemokines in tumor cells were significantly increased.

[0049] To clarify the above problems, we confirmed that GSDMD-N has tumor-killing function and potential innate immune chemotactic function. To construct new immune enhancers and tumor drugs through GSDMD-N plasmids, we use nanomaterials for packaging. In response, we designed a weak acid-responsive nanomaterial of Meo-PEG-b-PDPA.

Embodiment 3

[0050] Example 3 Synthesis of nanocarrier Meo-PEG-b-PDPA

[0051] ① Synthesis of brominated polyethylene glycol (Meo-PEG-Br).

[0052] Polyethylene glycol (Meo-PEG-OH) and triethylamine were dissolved in dichloromethane. In an ice-salt bath, α-bromoisobutyryl bromide was added dropwise. After stirring the reaction at room temperature for 24 hours, the reaction solution was washed with 1 mol / L sodium hydroxide and hydrochloric acid aqueous solution respectively, and finally washed with deionization. The organic phase was collected, dried over anhydrous magnesium sulfate, the solution was concentrated, and cold ether was added to precipitate the product. After repeated precipitation 3 times, the white powdery product was collected after vacuum drying. Figure 4 is the chemical structure and H NMR spectrum of Meo-PEG-Br.

[0053] ②Meo-PEG-b-PDPA was synthesized by atom transfer radical polymerization.

[0054] 2-(Diisopropylamino)ethyl methacrylate (DPA-MA, 2.6 g, 12 mmol), ...

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Abstract

The invention relates to the field of biological medicine, in particular to a nanometer material based on a loaded GSDMD protein N-terminal peptide fragment and application of the nanometer material. The invention provides a plasmid loaded with a GSDMD-N terminal nucleotide sequence. The GSDMD-N terminal nucleotide sequence is as shown in SEQ ID NO: 2. The invention also provides the GSDMD-N-PDPA nano material, the core of the GSDMD-N-PDPA nano material is the GSDMD-N plasmid, and the entrapment material of the GSDMD-N-PDPA nano material is the nano carrier PDPA. The GSDMD-N-PDPA nano material has the effects of killing tumors and enhancing the local immune function, the preparation cost is low, the core of the nano material is the GSDMD-N plasmid, the plasmid amplification operation is simple and convenient after preparation, and the preparation cost is low; the entrapment material is a nanometer material PDPA, so that the preparation cost is not high.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a nanomaterial based on the loaded GSDMD protein N-terminal peptide segment and its application. Background technique [0002] Tumor is the main killer of human beings in the 21st century. It is a complex disease caused by the interaction of environmental factors and genetic factors. There are many types of malignant tumors with different types, involved tissues and organs, different disease stages, and different responses to various treatments. Therefore, most patients need comprehensive treatment. The so-called comprehensive treatment refers to the comprehensive use of surgery, chemotherapy, radiotherapy, immunotherapy, traditional Chinese medicine treatment, interventional therapy, microwave therapy and other means according to the patient's physical condition, tumor pathological type, and scope of invasion, in order to greatly improve the cure. rate and improve the quality of life...

Claims

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Application Information

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IPC IPC(8): C12N15/85A61K48/00A61K38/17B82Y5/00A61P35/00A61P37/04
CPCA61K48/0041A61P35/00A61P37/04C12N15/85C07K14/4703A61K38/1761A61K48/005B82Y5/00C12N2800/107Y02A50/30
Inventor 黄子贤黄志权许小丁韦春芳易晨蔡佩娥蒋启明
Owner SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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