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Construction of nano-carrier for regulating adaptive cell and humoral immunity and application thereof

A technology of adaptive cells and nano-carriers, which is applied in the direction of antigen carriers, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., which can solve the problems of high preparation costs, lack of targeting methods, and unfavorable scale-up production, etc. question

Inactive Publication Date: 2021-07-27
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the lack of effective targeting means and suitable antigen delivery vehicles, the application of this strategy in anti-tumor, anti-virus and anti-infection is very limited.
Specifically, the structure of the antigen is crucial to the induction of a specific immune response, and the direct modification of the antigen by endoplasmic reticulum tropism molecules is likely to destroy the natural structure of the antigen, affecting the effectiveness and specificity of the immune response; at the same time, this direct The conjugation of the antigen puts higher requirements on the intracellular dissociation and release of the antigen; in addition, for different antigens, the way and degree of targeting modification are different, the preparation cost is high and difficult, and it is not conducive to scale-up production

Method used

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  • Construction of nano-carrier for regulating adaptive cell and humoral immunity and application thereof
  • Construction of nano-carrier for regulating adaptive cell and humoral immunity and application thereof
  • Construction of nano-carrier for regulating adaptive cell and humoral immunity and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Example 1 Prescription Screening, Antigen Loading and Cell Uptake of Cationic Nanoemulsion

[0048] (1) Prescription screening and physical and chemical properties characterization of blank nanoemulsion

[0049] Table 1: Recipe composition of nanoemulsion

[0050]

[0051] First, a blank nanoemulsion was prepared by emulsification ultrasonic method, and its prescription was screened. By changing the type of PC (PL100M and E-80), the proportion of each lipid component and the content of the water phase, a prescription with higher stability is screened out, namely prescription 8 (E80:VE:DOTAP=1.45%:1.45% :0.323%, w / w), for follow-up research (see figure 1 ). The nanoemulsion particle diameter under this prescription is about 200nm, and potential is about 60mV (dynamic light scattering method detects); Under transmission electron microscope (TEM), present typical emulsion form (see figure 2 ); high stability and easy storage, there is no significant change in parti...

Embodiment 2

[0056] Example 2 Preparation of cationic nanoemulsion loaded with model antigen OVA and surface modified p-dodecylbenzenesulfonamide and characterization of its endoplasmic reticulum targeting

[0057] (1) Endoplasmic reticulum-targeted surface modification of antigen-loaded cationic nanoemulsions

[0058] Composition of endoplasmic reticulum-targeted antigen-loaded cationic nanoemulsions

[0059] Yolk Lecithin E80 9mg

[0060] Vitamin E (VE) 9mg

[0061] (2,3-dioleoyl-propyl)trimethylammonium chloride (DOTAP) 1mg~28mg

[0062] p-dodecylbenzenesulfonamide 1mg~8mg

[0063] Aqueous solution of OVA (5 mg / mL) 0.6 mL.

[0064] In order to better realize the loading of the antigen and the targeted accumulation of the endoplasmic reticulum, the prescription 8 in the implementation example 1 was further adjusted: the aqueous solution of OVA was directly used as the water phase, and the oil phase of the cationic nanoemulsion was added with Endoplasmic reticulum tropism of p-dodecy...

Embodiment 3

[0067] Example 3 Verification of Endoplasmic Reticulum-targeted Antigen-Loaded Cationic Nanocarriers Improving Cellular Immunity and Humoral Immunity

[0068] Directly dissolving the antigenic protein in the aqueous phase of the emulsion is conducive to the internal loading and external adsorption of the antigen during the assembly process of the carrier, which can further increase the drug loading capacity of the antigen, promote the cellular uptake of the antigen, and thus up-regulate the cellular immunity mediated by DCs and overall responsiveness of humoral immunity. The endoplasmic reticulum targeting properties of the carrier are conducive to the selective accumulation of antigens in the endoplasmic reticulum of DCs, and mechanisms such as endoplasmic reticulum-related degradation can be used to promote the MHC class I presentation of exogenous antigens, thereby increasing the participation of cellular immunity.

[0069] In order to verify the advantages of this endoplas...

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Abstract

The invention provides construction of a nano-carrier for regulating body adaptive cell and humoral immunity and an application thereof. According to the nano-carrier disclosed by the invention, small molecules or polypeptides with endoplasmic reticulum tropism are modified on the surfaces of nano-particles loaded with antigens, and the total uptake amount, the transport path and the processing presentation mode of exogenous antigens in dendritic cells are changed, so that the cellular immunity and humoral immunity of the antigen specificity of a body are regulated and controlled. The nano-carrier disclosed by the invention can be a drug loading system such as cationic nano-emulsion, liposome or lipid nanoparticles, and the antigen can relate to tumor, virus or plasmodium specific antigen protein / polypeptide. The nano drug loading system mobilizes the anti-tumor, anti-virus or anti-parasitic infection specific immune response by improving the adaptive immunity of a body, especially the participation degree of cellular immunity, and has the characteristics of novel scheme, simple preparation and wide application range.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to a nano drug delivery system capable of enhancing the efficacy of a protein / polypeptide subunit vaccine and regulating the body's adaptive cellular and humoral immunity, and in particular to the construction of a nanocarrier capable of regulating adaptive cellular and humoral immunity. And the application of the nano-carrier in the preparation of anti-tumor, anti-virus and anti-parasitic infection drugs. Background technique [0002] The development of human society has been severely hit by tumors, viruses and infections many times, and the emergence of vaccines is an important turning point in artificially responding to the invasion of pathogenic substances. It is highly controllable, easy to popularize, and can be repeatedly vaccinated to enhance specific immune memory to provide Long-term protection and other advantages. Due to safety and production cost considerations, protein / peptide-b...

Claims

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Application Information

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IPC IPC(8): A61K39/385A61K47/24A61K47/22A61K47/44A61K47/14A61K47/26A61K47/06A61K47/18A61K47/28A61K47/54A61K47/62A61K47/69A61K39/00A61K39/12A61K31/215A61K39/015A61P35/00A61P31/12A61P31/14A61P33/00A61P33/06
CPCA61K39/385A61K47/24A61K47/22A61K47/44A61K47/14A61K47/26A61K47/06A61K47/186A61K47/28A61K47/18A61K47/54A61K47/62A61K47/6907A61K47/6911A61K47/6929A61K39/0011A61K39/00A61K39/12A61K39/015A61P35/00A61P31/12A61P31/14A61P33/00A61P33/06A61K2039/876A61K2039/884A61K2039/575A61K2039/6031A61K2039/60Y02A50/30
Inventor 游剑施莹莹李青坡姜新东
Owner ZHEJIANG UNIV
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