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Mannose modified co-loaded antigen and double immuno-agonist phospholipid hybrid polymer vesicle as well as preparation method and application thereof

An agonist and polymer technology, applied in the field of biomedical engineering, can solve the problems of vaccines that cannot produce immune response strength, limit anti-tumor efficiency, etc., and achieve the effect of protecting the body from instability, optimizing the immune effect, and having a small particle size.

Active Publication Date: 2018-12-11
INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Peptide and protein vaccines targeting tumors are thought to activate CD4 + T and CD8 + T cells, but such vaccines cannot generate sufficient immune response strength thus limiting their antitumor efficacy

Method used

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  • Mannose modified co-loaded antigen and double immuno-agonist phospholipid hybrid polymer vesicle as well as preparation method and application thereof
  • Mannose modified co-loaded antigen and double immuno-agonist phospholipid hybrid polymer vesicle as well as preparation method and application thereof
  • Mannose modified co-loaded antigen and double immuno-agonist phospholipid hybrid polymer vesicle as well as preparation method and application thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0038] The present invention provides a method for preparing phospholipid hybrid polymer vesicles co-carrying antigens and dual immune agonists, comprising steps:

[0039] S1: Dissolve the amphiphilic triblock copolymer PCL-b-PEG-b-PCL and the immune stimulant in an organic solvent; Ultrasonic cell disruptor was used to sonicate for 5 minutes, and the antigen solution was dropped into the sonication process to obtain the primary emulsion;

[0040] Wherein, the mass ratio of the amphiphilic triblock copolymer PCL-b-PEG-b-PCL and the immune stimulant is 20mg:2mg; the molecular weight of the amphiphilic triblock copolymer PCL-b-PEG-b-PCL It is 10000-24000, preferably 16000, wherein the mass percentage of PEG hydrophilic segment is greater than 45%; the amphiphilic triblock copolymer PCL-b-PEG-b-PCL is preferably PCL 4000 -PEG 8000 -PCL 4000 The immune stimulant is one or more of TLR4, TLR7 / 8, TLR1, TLR2, TLR5, TLR6, TLR3 and TLR9; preferably, the TLR7 / 8 agonist is IMQ and / or R...

Embodiment 1

[0052] This example provides a method for preparing phospholipid hybrid polymer vesicles co-loaded with antigens and dual immune agonists, including steps:

[0053] S1: 20 mg amphiphilic triblock copolymer PCL 4000 -PEG 8000 -PCL 4000 and 2mg of TLR7 / 8 agonist IMQ were dissolved in 1mL of dichloromethane; after fully dissolving, in an ice bath, ultrasonicated for 5min with a 3mm probe and an ultrasonic cell disruptor whose power was adjusted to 25% (16W). Inject 200 μL of 10 mg / mL OVA antigen solution to obtain a primary emulsion.

[0054] S2: Under the condition of magnetic stirring at 200rpm, drop the primary emulsion into 10mL of swollen polyvinyl alcohol (PVA) solution with a mass fraction of 2%, and the dropping time is 2min, then wash it with 1mL deionized water. Immediately, the cleaned mixture was ultrasonicated for 10 min with a 5mm probe and an ultrasonic cell disruptor with power adjusted to 30% (22W) in an ice bath to obtain a secondary emulsion.

[0055] S3: S...

Embodiment 2

[0059] This example provides a method for preparing phospholipid hybrid polymer vesicles co-loaded with mannose-targeted modified antigens and dual immune agonists, including steps:

[0060] S1: 20 mg amphiphilic triblock copolymer PCL 4000 -PEG 8000 -PCL 4000 and 2mg of TLR7 / 8 agonist IMQ were dissolved in 1mL of dichloromethane; after fully dissolved, under ice bath conditions, ultrasonic cell disruptor with 3mm probe and power adjusted to 25% (16W) was ultrasonicated for 5min. 200 μL of 10 mg / mL OVA antigen solution was added dropwise to obtain a primary emulsion.

[0061] S2: Under the condition of magnetic stirring at 200rpm, drop the primary emulsion into 10mL of swollen polyvinyl alcohol (PVA) solution with a mass fraction of 2%, and the dropping time is 2min, then wash it with 1mL deionized water. Immediately, the cleaned mixture was ultrasonicated for 10 min with a 5mm probe and an ultrasonic cell disruptor with power adjusted to 30% (22W) in an ice bath to obtain ...

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Abstract

The invention relates to a mannose modified co-loaded antigen and a double immuno-agonist phospholipid hybrid polymer vesicle as well as a preparation method and application thereof. A vaccine carriertakes an amphiphilic triblock copolymer as material, OVA is loaded in the hydrophilic inner cavity, IMQ is loaded in the hydrophobic membrane layer, DOTAP cationic layer is fitted with MPLA, and cationic lipid outer layer adsorbs outer layer OVA; phospholipid with reactive group is introduced to pass the targeted mannose ligand through covalently linked to the PEG-active distal end of the polymer-loaded vesicle surface, integrating the functions of active targeting of tumors, co-delivery of antigens and adjuvants and the like; the vesicle has the characteristics of small particle size, good dispersion, high antigen loading and good biocompatibility, etc., which can promote antigen uptake, DC activation and maturation, antigen cross-presentation, antigenic lymph node migration, lymphocyteactivation, effector T cell immune response, CD8<+> T and CD4<+> T cell responses, and memory T cells immune response.

Description

technical field [0001] The invention relates to the technical field of biomedical engineering, in particular to a mannose-modified co-loaded antigen and dual immune agonist phospholipid hybrid polymer vesicles and a preparation method and application thereof. Background technique [0002] Malignant tumors are currently a serious threat to human health, and the overall cure rate is less than 20%. The current clinical treatment methods for tumors mainly include surgical resection, chemotherapy and radiotherapy. These treatment methods often focus on local tumor lesions, and all of them have limitations. Surgical resection is ineffective for the treatment of metastatic tumors; chemotherapy and radiotherapy have severe side effects and seriously damage the patient's immune system. Tumor treatment has gone through traditional treatment to targeted therapy, and then to the latest cellular immunotherapy. Tumor immunotherapy has become the "fourth largest" tumor treatment method t...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/60A61K47/26A61K47/22A61K47/42A61K39/12A61K39/00A61K39/015A61K39/10A61K39/29A61P31/04A61P31/20A61P35/00A61P33/06
CPCA61K39/0011A61K39/015A61K39/099A61K39/12A61K47/22A61K47/26A61K47/42A61K47/60A61K47/6915A61P31/04A61P31/20A61P33/06A61P35/00C12N2710/20034C12N2730/10134Y02A50/30
Inventor 张琳华朱敦皖胡春艳樊帆张志明
Owner INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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