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Application of bee venom lipid nanoparticles

A lipid nanoparticle and nanoparticle technology, applied in the fields of biological science and drug carriers, can solve problems such as aggravating the patient's condition, cytotoxicity, and damage to the body's immune system, and achieve the effects of prolonging the survival rate and inhibiting growth.

Pending Publication Date: 2019-04-30
HUAZHONG UNIV OF SCI & TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are also defects in the drugs or drug carriers that directly kill tumor cells: the drugs or drug carriers that directly kill tumor cells generally have cytotoxicity. When killing tumor cells, they will also act on normal cells in the body, especially The body's immune cells, which damage the body's immune system and lead to tumor recurrence
Once drug resistance appears, it will not only make the drug treatment insensitive, but repeated multiple treatments will increase the toxicity of chemotherapy, aggravate the patient's condition, and reduce the patient's quality of life

Method used

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Experimental program
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Effect test

Embodiment 1

[0040] Embodiment 1: the application of bee venom lipid nanoparticles

[0041] An embodiment of the present invention provides an application of bee venom lipid nanoparticles, which are composed of bee venom hybrid polypeptides combined with phospholipids and cholesterol lipids. The melittin hybrid polypeptide is composed of α-helical polypeptide, connecting sequence and melittin in series in the form of covalent bonds. The amino acid sequence of the α-helical polypeptide is DWFKAFYDKVAEKFKEAF, and the amino acid sequence of the α-helical polypeptide is shown in SEQ ID NO.1 in the sequence listing. The amino acid sequence of the linker sequence is GSG. The phospholipid is dimyristoylphosphatidylcholine (DMPC, ie 1,2-dimyristoyl-sn-glycero-3-phosphocholine). The molar ratio of bee venom hybrid polypeptide, phospholipid and cholesteryl lipid is 0.19:3:0.2.

[0042] The bee venom lipid nanoparticles are used to prepare immune activation and anticancer agents, which target anti...

Embodiment 2

[0047] Embodiment 2: the preparation method of bee venom lipid nanoparticles

[0048] The embodiment of the present invention provides a preparation method of bee venom lipid nanoparticles, comprising the following steps:

[0049] S1. Mix 3 μmol DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and 0.2 μmol cholesteryl ester (Cholesteryl oleate, C.O for short) in chloroform fully in a glass test tube, and seal the test tube mouth with a parafilm ;

[0050] S2, dry the chloroform in the test tube in a stable nitrogen flow, so that the mixture in step S1 can form a thin film at the bottom of the test tube; put the test tube in a vacuum desiccator and vacuum dry for 1 h;

[0051] S3, add 1 mL of phosphate buffer solution to the test tube, fill it with nitrogen gas and seal it, and use a vortex shaker to fully resuspend the drug film at the bottom of the test tube to form a uniform milky white suspension; ultrasonicate the test tube at 48°C for 1 hour;

[0052] S4, using a syri...

Embodiment 3

[0054] Example 3: Comparison of the Killing Effects of Bee Venom Lipid Nanoparticles on Tumor Cells and Immune Cells

[0055] The killing effect of the melittin lipid nanoparticles prepared in Example 2 on tumor cells and immune cells was compared, and the immune cells were dendritic cells (DC) as an example.

[0056] figure 1 The results showed that after incubation of 10 μM lipid nanoparticles with tumor cells for 24 hours, the lethality almost reached 100%, but almost no toxicity to immune cells (dendritic cells). This shows that the meli venom lipid nanoparticles have no toxic effect on the antigen-presenting cells in the tumor microenvironment and even in the lymph nodes, on the contrary, they have a strong killing effect on tumor cells.

[0057] Targeting effect of meli venom lipid nanoparticles on lymph nodes, cf. figure 2 . Through fluorescence imaging, it was found that the lipid nanoparticles of bee venom can reach the draining lymph nodes smoothly, reaching the ...

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Abstract

The invention discloses an application of bee venom lipid nanoparticles, which relates to the technical field of biological science and a pharmaceutical carrier. The bee venom lipid nanoparticles of the invention are composed of bee venom hybrid polypeptide and phospholipid and cholersteryl ester. The immune activation and anticancer agent prepared by the bee venom lipid nanoparticles is used fortargeting antigen presenting cells, and activates antigen presenting cells to improve the immune microenvironment, so as to generate a systemic immune response and inhibit tumor growth and metastasiseffect; the agent is also used to target and activate dendritic cells, macrophages, and B cells to inhibit the production of distant tumors; and the agent is also used to target hepatic sinusoidal endothelial cells and induce them to release a variety of immune factors to inhibit tumor liver metastasis. The immune activation and anticancer agent prepared by the bee venom lipid nanoparticle has notoxic and side effects, does not depend on the tumor type, and has good anti-tumor effect.

Description

Technical field [0001] The invention relates to the technical fields of biological science and drug carriers, and specifically relates to the application of bee venom lipid nanoparticles. Background technique [0002] Cancer is a major disease that seriously endangers human health. Tumor metastasis and recurrence are the main causes of death in tumor patients. Chemotherapy for malignant tumors is one of the important means of tumor treatment, which is comparable to surgery and radiotherapy. It can achieve better clinical therapeutic effects in the short term. Its specific mechanism of action is mainly to interfere with the anabolism of nucleic acids, DNA replication, Inhibits mitosis and protein synthesis. However, drugs or drug carriers that directly kill tumor cells also have shortcomings: drugs or drug carriers that directly kill tumor cells generally have cytotoxic effects. While killing tumor cells, they will also act on normal cells in the body, especially The body's...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K9/127A61P35/00
CPCA61K9/127A61K38/17A61K47/28
Inventor 骆清铭张智红余祥
Owner HUAZHONG UNIV OF SCI & TECH
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