CN111494618A - Preparation method and application of chiral nano material adjuvant - Google Patents
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Abstract
The invention relates to a preparation method and application of a chiral nano-material adjuvant, belonging to the technical field of material biology.A chiral nano-material is prepared by a photosynthetic method, has high-efficiency adjuvant effect after being mixed with an immunostimulant, and is then mixed with a vaccine for injecting immune C57B L/6 mice at the back.
Description
Technical Field
The invention relates to a preparation method and application of a chiral nano-material adjuvant, belonging to the technical field of material biology.
Background
The immune adjuvant is an exogenous substance which does not stimulate an animal body to generate immune response, but can enhance the immunogenicity of an antigen and enhance the immune response of the body when being combined with the antigen. The most commonly used adjuvant in the current animal experiments is Freund adjuvant, but the Freund adjuvant is oil-soluble adjuvant, a complex emulsification process is needed when the Freund adjuvant is mixed with a water-soluble antigen, the immunization period is long, and toxic and side effects are often accompanied. Most of the clinically used adjuvants are aluminum adjuvants, but the aluminum adjuvants can only enhance the humoral immunity of the organism and have poor stability, so that a new material is required to be developed into a safe and efficient immunologic adjuvant.
Due to the excellent physical and chemical properties and good biocompatibility, part of the nano materials are widely applied to the field of biology. As an adjuvant, the surface characteristics of the nano material which is easy to modify enable the nano material to be combined with various immunostimulants or vaccines to play a better immune effect. However, most adjuvants do not distinguish their chiral properties, and in order to better adapt to the body and induce immune response, it is necessary to distinguish the chiral properties of the materials.
Disclosure of Invention
The invention aims to overcome the defects and provides a preparation method and application of a chiral nano-material adjuvant, which are simple in preparation process and good in effect.
The technical scheme of the invention is a preparation method of a chiral nano material adjuvant, which comprises the following steps:
(1) pretreatment of the reaction vessel: soaking the reaction bottle in aqua regia for 24h, cleaning and drying;
(2) preparing seeds: adding potassium iodide, a sodium chloroaurate solution and ascorbic acid into a hexadecyltrimethylammonium chloride aqueous solution with a certain concentration, finally adding sodium hydroxide, quickly mixing, and standing;
(3) the method comprises the following steps of (1) performing photosynthesis on the chiral nano material, namely adding chloroauric acid, ascorbic acid, L type or D type cysteine-phenylalanine dipeptide and concentrated seed solution into hexadecyl trimethyl ammonium bromide aqueous solution, quickly and uniformly stirring, placing the solution under circularly polarized light with the wavelength of 594nm for irradiation, and modifying sulfhydryl polyethylene glycol to obtain the chiral nano material;
(4) preparing a chiral nano material adjuvant: and (4) freeze-drying the chiral nano material obtained in the step (3) into powder, dissolving the powder by a certain mass, and fully mixing the dissolved solution with an immunostimulant to obtain the chiral nano material adjuvant.
The method comprises the following specific steps:
(1) pretreatment of the reaction vessel: firstly, soaking a reaction bottle in aqua regia for 24 hours, cleaning and airing;
(2) the seeds are prepared by adding 75 mu L, 10mM potassium iodide solution, 100.4 mu L sodium chloroaurate, 80 mu L, 64mM ascorbic acid to 9.6M L, 16.7mM cetyltrimethylammonium chloride aqueous solution, mixing, adding 10 mu L, 0.1M sodium hydroxide, stirring rapidly for 20s, standing for 10min to form seeds, centrifuging the seed solution at 8000rpm for 5min, concentrating 20 times, and dissolving in 1mM cetyltrimethylammonium bromide aqueous solution for further growth;
(3) the chiral nano material is prepared by adding 0.2m L and 10mM of chloroauric acid into 4.75m L, 1.7mM of hexadecyl trimethyl ammonium bromide aqueous solution, standing for 10min, adding 0.475m L and 40mM of ascorbic acid, mixing, adding 5 mu L and 4mM of L type or D type cysteine-phenylalanine dipeptide and 50 mu L concentrated seed solution, stirring rapidly, placing the solution at 84mW/cm optical density2Irradiating with 594nm circularly polarized light for 30minCentrifuging and concentrating the solution after injection by 40 times, adding sulfhydryl polyethylene glycol until the final concentration is 0.2nM, and obtaining the chiral nano material after 4 h;
(4) preparing a chiral nano material adjuvant: freeze-drying the chiral nano material obtained in the step (3) for 6-12 hours at-10 to-50 ℃ and 1.3-13Pa to obtain powder; according to the chiral nano material: the immunostimulant is fully mixed according to the mass ratio of 25-600:1 to obtain the chiral nano material adjuvant.
Further, in the step (3), when L-type cysteine-phenylalanine dipeptide is added, the irradiated polarized light is left circularly polarized light, and when D-type cysteine-phenylalanine dipeptide is added, the irradiated polarized light is right circularly polarized light.
Further, the immunostimulant in step (4) is specifically monophosphoryl lipid A, lipopolysaccharide, CpG oligonucleotide or poly (I: C) interferon inducer.
The application of the chiral nano material adjuvant prepared by the method can stimulate a mouse to generate corresponding cellular immunity and humoral immunity response after the chiral nano material adjuvant is mixed with the vaccine to immunize the mouse.
Further, the chiral nanomaterial adjuvant and the vaccine are mixed according to the mass ratio of 500-3000: 5-30 mixing well for immunizing mice.
Further, the vaccine is ovalbumin OVA, bovine serum albumin BSA, hemocyanin K L H or human serum albumin HSA.
The invention has the beneficial effects that: the chiral nano material adjuvant can be mixed with an immunostimulant for use, so that the specific immune response of a mouse to a certain antigen is enhanced, the preparation process is simple, and the effect is good.
Drawings
FIG. 1 shows chiral signals of the nanomaterial in example 1 of the present invention.
FIG. 2 is a graph showing the measurement of relevant immune indexes in spleen and serum of a mouse 7 days later in example 2 of the present invention.
Detailed Description
The following examples are provided as further illustration of the invention and are not to be construed as limitations or limitations of the invention. The invention is further illustrated by the following examples.
According to the invention, L type chiral nano materials with adjuvant potential and an immunostimulant are mixed according to a certain proportion to prepare the chiral nano adjuvant, the chiral nano adjuvant is mixed with a vaccine to prepare a mouse for subcutaneous immunization, and the mouse immunized by L type chiral nano adjuvant shows a good immune effect.
Example 1 Synthesis of chiral nanomaterial adjuvant
The reaction bottle is soaked in aqua regia for 24h, washed and dried, 75 mu L and 10mM potassium iodide solution, 100.4 mu L sodium chloroaurate and 80 mu L and 64mM ascorbic acid are added into 9.6M L and 16.7mM hexadecyltrimethylammonium chloride aqueous solution, 10 mu L and 0.1M sodium hydroxide are added after mixing, the mixture is rapidly stirred for 20s and stands for 10min to generate seeds, the seed solution is centrifuged (8000 rpm and 5 min), and 20 times of the seed solution is concentrated and dissolved in 1mM hexadecyltrimethylammonium bromide aqueous solution for next growth.
Adding 0.2m L mM and 10mM chloroauric acid into 4.75m L mM and 1.7mM hexadecyl trimethyl ammonium bromide aqueous solution, standing for 10min, adding 0.475m L mM and 40mM ascorbic acid, mixing, adding 5 mu L mM L type or D type cysteine-phenylalanine dipeptide and 50 mu L concentrated seed solution, stirring rapidly, placing the solution in 84mW/cm optical density2Irradiating the solution with polarized light of a left circle (L type) or a right circle (D type) with the wavelength of 594nM for 30min, centrifugally concentrating the irradiated solution (4200 rpm, 3 min) by 40 times, adding thioglycol until the final concentration is 0.2nM, obtaining the (L type or D type) chiral nano material with adjuvant potential after 4h, and carrying out signal detection on the material.
The chiral signal is shown in figure 1, wherein figure 1-a is the signal of L type chiral nano material adjuvant, and figure 1-b is the signal of D type chiral nano material adjuvant.
Example 2 application of chiral nanomaterial adjuvant
The chiral nanomaterial synthesized in example 1 is concentrated and freeze-dried into powder, 2mg of chiral nanomaterial adjuvant and 10 μ g of monophosphoryl lipid a are dissolved in 100 μ L phosphate buffer and mixed with vaccine to immunize mice, and chicken Ovalbumin (OVA) is taken as an example, the chiral nanomaterial adjuvant and 20 μ g of OVA are mixed to obtain L type chiral immune antigen and D type chiral immune antigen.
Three groups of C57B L/6 mice were taken, subcutaneous immune antigen and Phosphate Buffered Saline (PBS), L type chiral immune antigen and D type chiral immune antigen were respectively detected 7 days later, and the specific results are shown in FIG. 2.
FIG. 2-a is mouse spleen CD4+TNF-α+Expression level of T cells, FIG. 2-b shows mouse spleen CD4+IFN-γ+Expression level of T cells, FIG. 2-c shows mouse spleen CD8+TNF-α+Expression level of T cells, FIG. 2-d shows mouse spleen CD8+IFN-γ+The expression level of T cells; FIG. 2-e is OVA-specific antibody titers in mouse sera.
According to experimental results, the L type chiral nanomaterial adjuvant can induce an organism to generate stronger humoral immunity and cellular immunity.
Although the present invention has been described with reference to the preferred embodiments, it should be understood that various changes and modifications can be made therein by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (7)
1. A preparation method of a chiral nano material adjuvant is characterized by comprising the following steps:
(1) pretreatment of the reaction vessel: soaking the reaction bottle in aqua regia for 24h, cleaning and drying;
(2) preparing seeds: adding potassium iodide, a sodium chloroaurate solution and ascorbic acid into a hexadecyltrimethylammonium chloride aqueous solution with a certain concentration, finally adding sodium hydroxide, quickly mixing, and standing;
(3) the chiral nano material is prepared through the steps of adding chloroauric acid, ascorbic acid, L type or D type cysteine-phenylalanine dipeptide and concentrated seed solution into hexadecyl trimethyl ammonium bromide water solution, fast stirring, irradiating the solution under circular polarized light of wavelength 594nm, and modifying mercapto polyethylene glycol to obtain chiral nano material;
(4) preparing a chiral nano material adjuvant: and (4) freeze-drying the chiral nano material obtained in the step (3) into powder, dissolving the powder by a certain mass, and fully mixing the dissolved solution with an immunostimulant to obtain the chiral nano material adjuvant.
2. The preparation method of the chiral nanomaterial adjuvant according to claim 1, characterized by comprising the following steps:
(1) pretreatment of the reaction vessel: firstly, soaking a reaction bottle in aqua regia for 24 hours, cleaning and airing;
(2) the seeds are prepared by adding 75 mu L, 10mM potassium iodide solution, 100.4 mu L sodium chloroaurate, 80 mu L, 64mM ascorbic acid to 9.6M L, 16.7mM hexadecyltrimethylammonium chloride aqueous solution, mixing, adding 10 mu L, 0.1M sodium hydroxide, stirring rapidly for 20s, standing for 10min to form seeds, centrifuging the seed solution at 8000rpm for 5min, concentrating 20 times, and dissolving in 1mM hexadecyltrimethylammonium bromide aqueous solution for further growth;
(3) the chiral nano material is prepared by adding 0.2m L mM and 10mM of chloroauric acid into 4.75m L and 1.7mM of hexadecyl trimethyl ammonium bromide aqueous solution, standing for 10min, adding 0.475m L mM and 40mM of ascorbic acid, mixing, adding 5 mu L mM and 4mM of L type or D type cysteine-phenylalanine dipeptide and 50 mu L concentrated seed solution, rapidly stirring, placing the solution in 84mW/cm optical density2Irradiating for 30min under polarized light with wavelength of 594nM, centrifuging and concentrating the irradiated solution by 40 times, adding mercaptopolyethylene glycol until the final concentration is 0.2nM, and obtaining chiral nano material after 4 h;
(4) preparing a chiral nano material adjuvant: freeze-drying the chiral nano material obtained in the step (3) for 6-12 hours at-10 to-50 ℃ and 1.3-13Pa to obtain powder; according to the chiral nano material: the immunostimulant is fully mixed according to the mass ratio of 25-600:1 to obtain the chiral nano material adjuvant.
3. The method for preparing the chiral nanomaterial adjuvant according to claim 1, wherein in the step (3), when L-type cysteine-phenylalanine dipeptide is added, the irradiated polarized light is left circularly polarized light, and when D-type cysteine-phenylalanine dipeptide is added, the irradiated polarized light is right circularly polarized light.
4. The method for preparing the chiral nanomaterial adjuvant according to claim 1, wherein: the immunostimulant in the step (4) is monophosphoryl lipid A, lipopolysaccharide, CpG oligonucleotide or poly (I: C) interferon inducer.
5. The use of the chiral nanomaterial adjuvant prepared by the method of any one of claims 1 to 4, characterized in that: the chiral nano material adjuvant is mixed with the vaccine to immunize a mouse, so that the mouse can be stimulated to generate corresponding cellular immunity and humoral immunity response.
6. The use of the chiral nanomaterial adjuvant prepared by the method of any one of claims 1 to 4, characterized in that: mixing a chiral nano material adjuvant with a vaccine according to a mass ratio of 500-3000: 5-30 mixing well for immunizing mice.
7. The use of the chiral nanomaterial adjuvant of claim 5, wherein the vaccine is ovalbumin OVA, bovine serum albumin BSA, hemocyanin K L H, or human serum albumin HSA.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114309636A (en) * | 2021-12-28 | 2022-04-12 | 江南大学 | Chiral gold nano antibacterial material and preparation method thereof |
| CN114522226A (en) * | 2022-02-14 | 2022-05-24 | 江南大学 | Chiral tumor nano vaccine and application thereof |
| WO2023091795A1 (en) * | 2021-11-22 | 2023-05-25 | The Regents Of The University Of Michigan | Modulation and utilization of enantiomer-dependent immunological response to chiral nanoparticles |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023091795A1 (en) * | 2021-11-22 | 2023-05-25 | The Regents Of The University Of Michigan | Modulation and utilization of enantiomer-dependent immunological response to chiral nanoparticles |
| CN114309636A (en) * | 2021-12-28 | 2022-04-12 | 江南大学 | Chiral gold nano antibacterial material and preparation method thereof |
| CN114309636B (en) * | 2021-12-28 | 2024-01-19 | 江南大学 | Chiral gold nano antibacterial material and preparation method thereof |
| CN114522226A (en) * | 2022-02-14 | 2022-05-24 | 江南大学 | Chiral tumor nano vaccine and application thereof |
| CN114522226B (en) * | 2022-02-14 | 2024-01-26 | 江南大学 | Chiral tumor nano vaccine and application thereof |
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