Apolipoprotein modified bionic nano tumor vaccine as well as preparation method and application thereof

Apolipoprotein and tumor vaccine technology, applied in the field of bionic nano-tumor vaccine and its preparation, can solve the problems of inefficient migration of antigens and adjuvants, failure of vaccine clinical trials, low immunogenicity, etc., to prevent degradation and promote antigenicity The effect of presenting and promoting antigen presentation

Inactive Publication Date: 2021-03-30
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The tumor vaccines currently on the market and under development in China can be roughly divided into four categories, including: whole cell vaccines, tumor peptide vaccines, genetically engineered vaccines, and antibody tumor vaccines;

Method used

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  • Apolipoprotein modified bionic nano tumor vaccine as well as preparation method and application thereof
  • Apolipoprotein modified bionic nano tumor vaccine as well as preparation method and application thereof
  • Apolipoprotein modified bionic nano tumor vaccine as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] Example 1: Preparation and Characterization of R837-αOVA-ApoE3-HNP

[0065] Prepare R837-loaded PLGA nanoparticles by emulsified solvent evaporation method; weigh 20 mg R837 and dissolve in 10 mL DMSO to obtain R837 stock solution; measure 50 μL R837 stock solution, 950 μL dichloromethane in a 5 mL EP tube, mix Slowly add 2mL of 1% sodium cholate solution to the wall, ultrasonicate for 2.4min with a probe in a water bath at 0°C, and the ultrasonic power is 220W. Add the obtained emulsion into 8mL of 0.5% sodium cholate solution, stir and disperse fully, remove the organic solvent methylene chloride on a rotary evaporator; centrifuge the nanoparticle solution at 14000rpm at 4°C for 45min, and discard the supernatant , the precipitate was resuspended in water to obtain the nano-core (R837-NP) loaded with R837; weigh 2mg of DMPC and place it in a 250mL round bottom flask, add 4mL of chloroform, put it on a rotary evaporator and vacuumize for 1h, and the temperature of the ...

Embodiment 2

[0068] Example 2: The modification of ApoE3 promotes the uptake of nanoparticles by BMDC

[0069] Prepare the preparation of entrapped fluorescent dye coumarin 6 (cou-6), replace R837 in the NP preparation process with cou6, add in the ratio of 10 mg PLGA, 10 μg cou-6, and the rest of the preparation method is the same as in Example 1; The 6-day-old BMDC cells were transferred to a flow tube, centrifuged at 2000rpm to discard the supernatant, added culture medium of different nano-preparations to resuspend and mix evenly, the concentrations of several nano-preparations were calculated as cou6, all were 50ng / mL, and placed at 37°C Incubate on a shaker for 30 minutes, discard the supernatant by centrifugation, wash once with PBS, resuspend with 100 μl CD11c antibody solution, incubate on ice for 30 minutes, resuspend the flow cytometer to detect the fluorescence intensity of D11c positive cells uptake of cou6;

[0070] Investigation time and concentration: BMDC cells were resusp...

Embodiment 3

[0074] Embodiment 3: Research on the uptake mechanism of nanoparticles modified by ApoE3 on BMDC

[0075] In order to further explore the uptake mechanism of ApoE3-modified biomimetic nano-preparations by BMDC, macropinocytosis marker FITC-dextran, caveolin-mediated endocytosis marker AF647-Cholera toxin, clathrin-mediated endocytosis marker TexasRed-Transferrin, co-cultured with fluorescent agents to investigate their transport pathways; including: BMDCs added ApoE3-modified biomimetic nano-preparations loaded with fluorescent dyes, and fluorescent-labeled endocytic markers, after Hochest33258, qualitative observation of nanoparticles under an inverted fluorescence microscope Co-localization of preparations and endocytic markers, and calculation of co-localization coefficients;

[0076] Use a variety of uptake pathway inhibitors to conduct uptake inhibition experiments on BMDC cells to investigate the mechanism of BMDC cells uptake ApoE3 modified nano preparations. Take BMDC ...

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Abstract

The invention belongs to the technical field of biological pharmacy, and relates to an apolipoprotein modified bionic nano tumor vaccine as well as a preparation method and an application thereof. Based on the characteristics of dendritic cell (DC) phagocytic antigen, the bionic nano tumor vaccine is prepared, and the bionic nano tumor vaccine utilizes a macropinocytosis approach to increase the intake of DC to the vaccine, promote the maturation and antigen presentation of DC and improve the immune response effect in vivo. According to the nano vaccine, a biodegradable material is used as a nano core to encapsulate a hydrophobic immunologic adjuvant, lipid is used as a shell to load tumor-associated antigen peptides, and apolipoprotein is modified on the lipid, so that DC is efficiently activated to phagocytize the nano vaccine by utilizing a macropinocytosis pathway. The nanoformulation vaccine is suitable for preventing or treating tumors against one or more antigens or adjuvants.

Description

technical field [0001] The invention belongs to the technical field of biopharmaceuticals, and relates to a biomimetic nano tumor vaccine modified by apolipoprotein and its preparation method and application. The biomimetic nano-vaccine has a core-shell structure, mainly including the inner nano-core and the outer lipid structure, and uses apolipoprotein to modify the surface of the biomimetic nano-vaccine: the biomimetic nano-vaccine can efficiently activate the DC macropinocytosis pathway, Promote DC to take up nanovaccine in large quantities. Background technique [0002] Malignant tumors are recognized as one of the most serious diseases to human health in the world. Scientists in this field have done a lot of research on this, and have achieved certain results, but they have not yet achieved the desired effect, especially for tumor metastasis. And recurrence, so far, better therapeutic interventions are still needed in clinical practice. With the development of immuno...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/42A61K47/34A61K47/24A61K39/00A61K39/39A61P35/00
CPCA61K9/5123A61K9/5153A61K9/5169A61K39/0011A61K39/39A61K2039/55511A61P35/00
Inventor 陈钧周松雷
Owner FUDAN UNIV
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