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A kind of nano vaccine and preparation method thereof

A nano-vaccine and self-assembly technology, applied in nanotechnology, nanotechnology, nanomedicine, etc., can solve the problem of reducing the efficacy of adjuvant/tumor-specific antigen-peptide combination therapy, and cannot guarantee the simultaneous acceptance of immune adjuvant and tumor-specific Antigenic peptides, increased immune-related toxic and side effects, etc.

Active Publication Date: 2021-11-19
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The current immune adjuvant nanomedicine is mainly in the form of nanocarrier-coated adjuvant single-drug, without forming a connection with the tumor-specific antigen peptide, and it cannot be guaranteed that the same DC can receive the immune adjuvant and tumor-specific antigen peptide at the same time, which will reduce the Efficacy of Adjuvant / Tumor-Specific Antigen Peptide Combination Therapy, Simultaneously Increased Immune-Related Toxicities

Method used

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  • A kind of nano vaccine and preparation method thereof
  • A kind of nano vaccine and preparation method thereof
  • A kind of nano vaccine and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] A preparation method of nano vaccine, comprising the steps of:

[0050] 1. Synthesis of polypeptide-maleimide-docosahexaenoic acid / peptide-mal-DHA

[0051] 1.1 Prepare the antigen peptide for later use, the N-terminal of the antigen is connected to the -Cys-(a)-(b) sequence, (a) is a hydrophilic group, and (b) is a cathepsin cleavage site group;

[0052] 1.2N-(2-Aminoethyl)maleimide and docosahexaenoic acid undergo a condensation reaction to obtain an intermediate product I;

[0053] 2,2'-Dithiodiethanol and docosahexaenoic acid are dissolved in dichloromethane, the condensing agent is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, the base is Under the condition of N,N-diisopropylethylamine, the reaction was carried out at 43°C for 24 hours, the solvent was spin-dried, and the intermediate product I (DHA-mal) was obtained after separation and extraction through a silica gel column;

[0054] 1.3 The final product peptide-mal-DHA is obtained by Michael addition reactio...

Embodiment 2

[0067] The preparation method of embodiment 2 nano vaccine

[0068] (A) A linker sequence CSSVVR was added to the front of the sequence of model antigen ovalbumin (ovalbumin, OVA, amino acid sequence SIINFEKL) 257-264, which was synthesized by Zhejiang Ontolais Biotechnology Co., Ltd.;

[0069] N-(2-aminoethyl)maleimide and linolenic acid are subjected to a condensation reaction to obtain an intermediate product I, and then the intermediate product I and the antigen are subjected to a Michael addition reaction to obtain OVA covalently coupled linolenic acid: wherein The cysteine ​​on C is used to connect the highly hydrophobic DHA, so that the modified peptide is in the form of one end hydrophobic and one end hydrophilic, which is conducive to the formation of self-assembled nanoparticles; the VVR sequence is the cleavage site of cathepsin S , when the nano-vaccine particles were endocytized by DC cells, the model antigen OVA was released under the action of cathepsin S in the...

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Abstract

The invention relates to a multi-component carrier-free integrated nano-vaccine comprising antigenic peptides, immune adjuvants and small molecule drugs established by using unsaturated fatty acids and a method thereof. The nano-vaccine of the present invention includes an antigen, an immune adjuvant and an unsaturated fatty acid, the antigen is covalently coupled to the unsaturated fatty acid through a -SH group, and the immune adjuvant is coupled to the unsaturated fatty acid through an S-S bond. The invention utilizes unsaturated fatty acids to modify tumor-targeted antigen peptides and immune adjuvants, and uses unsaturated fatty acids as hydrophobic cores for self-assembly in aqueous solution, and the hydrophobic cores can also be loaded with highly hydrophobic small-molecule drugs. The nano-vaccine can increase the residence time of the antigen peptide in the lymph node, increase the endocytosis of the antigen peptide by DC cells, and improve the anti-tumor immune effect.

Description

technical field [0001] The invention relates to the technical field of medicine and biology, in particular to the technical field of vaccines; in particular, it relates to a multi-component carrier-free integrated nano-vaccine comprising antigenic peptides, immune adjuvants and small molecule drugs established by using unsaturated fatty acids. Background technique [0002] With the intensification of factors such as population aging, the incidence and mortality of cancer in my country continue to rise. Cancer has become the main cause of death in my country, seriously endangering the health of the Chinese people. In recent years, anti-tumor immunotherapy has developed rapidly, especially immune checkpoint inhibitor therapy (eg: PD-1 inhibitor and CTLA-4 inhibitor) has achieved significant clinical efficacy. The main principle of immune checkpoint inhibitor therapy is to block the immunosuppressive complexes (such as PD-1 / PD-L1, CTLA-4 / B7 complex), thereby releasing the imm...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/00A61K39/39A61K45/06A61K47/54A61P37/04B82Y5/00
CPCA61K39/0005A61K39/39A61K45/06A61K47/542A61P37/04B82Y5/00
Inventor 乔逸婷郑树森陈健翔张乐乐
Owner ZHEJIANG UNIV