阅读说明：本技术 一种量子点改性蛋白疫苗及其制备方法和应用 (Quantum dot modified protein vaccine and preparation method and application thereof ) 是由 曲松楠 汤子康 梁桃 邓初夏 雷海鹏 于 2021-06-30 设计创作，主要内容包括：本发明公开了一种量子点改性蛋白疫苗及其制备方法和应用,涉及纳米材料和生物医学领域。该量子点改性蛋白疫苗,其原料包括量子点粒子和抗原蛋白,量子点粒子的表面包含有生物相容性官能团,抗原蛋白与官能团作用使蛋白通过非共价键作用缠绕至量子点粒子的表面。本申请中通过量子点对抗原蛋白进行改性,可改变其空间构象,这些构象修饰导致正常蛋白质的免疫原性显着增强,同时使癌细胞上的免疫抑制蛋白质功能失调。有利于增强其被特异性识别的几率。这种量子点改性蛋白疫苗可以大幅度提高蛋白的免疫原性,进而具有更佳的免疫激活特性,其制备方法简单,操作条件温和。获得的量子点改性蛋白疫苗能够应用到癌症的个性化免疫治疗中。(The invention discloses a quantum dot modified protein vaccine and a preparation method and application thereof, and relates to the field of nano materials and biomedicine. The raw materials of the quantum dot modified protein vaccine comprise quantum dot particles and antigen protein, wherein the surfaces of the quantum dot particles comprise biocompatible functional groups, and the antigen protein and the functional groups act to enable the protein to be wound on the surfaces of the quantum dot particles through non-covalent bond action. In the application, the spatial conformation of the antigen protein can be changed by modifying the antigen protein through quantum dots, and the conformational modifications lead to the remarkable enhancement of the immunogenicity of normal protein and simultaneously cause the dysfunction of immunosuppressive protein on cancer cells. The probability of specific recognition of the protein is enhanced. The quantum dot modified protein vaccine can greatly improve the immunogenicity of protein, and further has better immune activation characteristic, and the preparation method is simple and the operation condition is mild. The obtained quantum dot modified protein vaccine can be applied to personalized immunotherapy of cancers.)

1. The quantum dot modified protein vaccine is characterized in that raw materials comprise quantum dot particles and antigen protein, the surfaces of the quantum dot particles comprise biocompatible functional groups, and the antigen protein and the functional groups act to enable the protein to be wound on the surfaces of the quantum dot particles through non-covalent bond action.

2. The quantum dot modified protein vaccine of claim 1, wherein the biocompatible functional group comprises one or more of hydroxyl, carboxyl, thiol, and amino groups.

3. The quantum dot modified protein vaccine of claim 1, wherein the antigenic protein is a whole-target protein vaccine with immunogenicity;

preferably, the antigen type of the whole target protein vaccine is selected from the group consisting of total protein digested by tumor tissues or total protein digested by tumor cell membranes;

preferably, the antigen type of the whole target protein vaccine is selected from one or more of tumor tissue digestive protein, proliferation protein and tumor cell line differentiation protein.

4. The quantum dot modified protein vaccine of claim 1, wherein the antigenic protein is a whole protein vaccine extracted from tumor cells of an individual with a tumor;

preferably, the individual having a tumor is a mammal;

preferably, the mammal is a human;

preferably, the mammal is a non-human mammal;

preferably, the non-human mammal is selected from any one of a mouse, rat, dog, pig, rabbit, cow, horse, sheep, monkey, and ape.

5. A preparation method of a quantum dot modified protein vaccine is characterized by comprising the step of modifying antigen protein by using quantum dot particles containing biocompatible functional groups so that the protein is wound on the surfaces of the quantum dot particles through non-covalent bond action.

6. The method for preparing the quantum dot modified protein vaccine according to claim 5, wherein the modification comprises mixing the solution of the quantum dot particles and the antigen protein, and reacting at 25-100 ℃ for 1-30 min;

preferably, stirring is carried out at 40-250rpm simultaneously during the modification reaction.

7. The method for preparing the quantum dot modified protein vaccine according to claim 6, wherein the mass ratio of the quantum dot particles to the antigen protein is 1: 0.10-10000;

preferably, the concentration of the solution of quantum dot particles is 0.1-1.5 mg/mL.

8. The method for preparing a quantum dot modified protein vaccine according to claim 5, wherein the method for preparing the quantum dot particles comprises:

mixing and dissolving a precursor carbon source and a functional raw material in a solvent, heating and reacting for 2-10h at the temperature of 110-220 ℃, cleaning and carrying out solid-liquid separation, and drying a separated solid product;

preferably, the precursor carbon source comprises at least one of citric acid, glucose and polyethylene glycol;

the functionalized raw material comprises at least one of urea, biuret and triurea;

preferably, the reaction system is cleaned by adopting an alcoholic solution, and the separated solid product is washed by water and centrifuged;

preferably, the alcohol solution comprises methanol or ethanol;

preferably, the centrifugation rotation speed is 6000-10000 rpm.

9. Use of the quantum dot modified protein vaccine of any one of claims 1-4 or the quantum dot modified protein vaccine of any one of claims 5-8 for the preparation of a tumor specific immune medicament.

10. An application of quantum dots in preparing a modified protein vaccine of a tumor specific immunity medicine.

Technical Field

The invention relates to the field of nano materials and biomedicine, in particular to a quantum dot modified protein vaccine and a preparation method and application thereof.

Background

Cancer is one of the leading causes of death worldwide. Cancer cells exhibit highly different mutant compositions and have limited overlap between different patients. Personalized cancer vaccines are a vaccine strategy vigorously developed in cancer immunotherapy aimed at modulating the innate and adaptive immune system to widely activate anti-cancer immunity with individual cancer neoantigens. Currently, the process of identifying and recombinantly producing specific neoantigens is very expensive and time consuming, during which the change in neoantigen will result in an ineffective anti-cancer response. In addition, anti-cancer vaccines directed against multiple neoantigens are considered more effective as anti-inflammatory vaccines directed against only a single cancer neoantigen. However, designing and producing personalized multi-target cancer vaccines is extremely challenging.

In recent developments, a number of strategies have been proposed to enhance the immunogenicity of cancer cells by coupling to adjuvants or blocking immunosuppressive proteins on cancer cells. However, these methods do not inherently alter or enhance the immunogenicity of cancer cells to a large extent.

In view of this, the invention is particularly proposed.

Disclosure of Invention

The invention aims to provide a quantum dot modified protein vaccine which is greatly improved in immunogenicity and has better immune activation characteristics.

The invention aims to provide a preparation method of a quantum dot modified protein vaccine, which is simple and has mild operation conditions.

The invention aims to provide application of a quantum dot modified protein vaccine in preparation of a tumor specific immune medicament.

The invention is realized by the following steps:

in a first aspect, the invention provides a quantum dot modified protein vaccine, raw materials of which comprise quantum dot particles and antigen proteins, wherein the surfaces of the quantum dot particles comprise biocompatible functional groups, and the antigen proteins and the functional groups act to enable the proteins to be wound on the surfaces of the quantum dot particles through non-covalent bond action.

In alternative embodiments, the biocompatible functional group comprises one or more of a hydroxyl group, a carboxyl group, a thiol group, and an amino group.

In alternative embodiments, the antigenic protein is a whole-target protein vaccine with immunogenicity;

preferably, the antigen type of the whole target protein vaccine is selected from the group consisting of total protein digested by tumor tissues or total protein digested by tumor cell membranes;

preferably, the antigen type of the whole target protein vaccine is selected from one or more of tumor tissue digestive protein, proliferation protein and tumor cell line differentiation protein.

In alternative embodiments, the antigenic protein is a whole protein vaccine extracted from tumor cells of an individual with a tumor;

preferably, the individual having a tumor is a mammal;

preferably, the mammal is a human;

preferably, the mammal is a non-human mammal;

preferably, the non-human mammal is selected from any one of a mouse, rat, dog, pig, rabbit, cow, horse, sheep, monkey, and ape.

In a second aspect, the present invention provides a method for preparing a quantum dot modified protein vaccine, which comprises modifying an antigen protein with a quantum dot comprising a biocompatible functional group such that the protein is bound to the surface of the quantum dot particle by non-covalent bond interaction.

In an alternative embodiment, the modification comprises mixing the solution of the quantum dot particles and the antigen protein and reacting for 1-30min at 25-100 ℃;

preferably, stirring is carried out at 40-250rpm simultaneously during the modification reaction.

In an alternative embodiment, the mass ratio of the quantum dot particle to the antigenic protein is 1: 0.10-10000;

preferably, the concentration of the solution of quantum dot particles is 0.1-1.5 mg/mL.

In an alternative embodiment, the method of preparing the quantum dot particle includes:

mixing and dissolving a precursor carbon source and a functional raw material in a solvent, heating and reacting for 2-10h at the temperature of 110-220 ℃, cleaning and carrying out solid-liquid separation, and drying a separated solid product;

preferably, the precursor carbon source comprises at least one of citric acid, glucose and polyethylene glycol;

the functionalized raw material comprises at least one of urea, biuret and triurea;

preferably, the reaction system is cleaned by adopting an alcoholic solution, and the separated solid product is washed by water and centrifuged;

preferably, the alcohol solution comprises methanol or ethanol;

preferably, the centrifugation rotation speed is 6000-10000 rpm.

In a third aspect, the present invention provides an application of the quantum dot modified protein vaccine according to the foregoing embodiment in preparing a tumor-specific immune drug.

In a fourth aspect, the invention provides an application of quantum dots in preparing a modified protein vaccine for tumor-specific immune drugs.

The invention has the following beneficial effects:

the quantum dot modified protein vaccine provided by the application has the advantages that the active functional groups on the surfaces of the quantum dots are reacted with the antigen protein, and the ultra-small quantum dots can modify the conformation structure of the protein again, so that the protein is wound on the surfaces of the quantum dots through the non-covalent bond action under the action of heat generated by external energy, and the protein vaccine combined by the quantum dots and the tumor protein is formed. The spatial conformation of the antigen protein can be changed by modifying the quantum dots, and the conformational modifications lead to the remarkable enhancement of the immunogenicity of the normal protein and simultaneously cause the dysfunction of the immunosuppressive protein on cancer cells. The probability of specific recognition of the protein is enhanced. The quantum dot modified protein vaccine can greatly improve the immunogenicity of protein, and further has better immune activation characteristic, and the preparation method is simple and the operation condition is mild. The obtained quantum dot modified protein vaccine can be applied to personalized immunotherapy of cancers.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.

FIG. 1 is a schematic structural diagram of interaction between quantum dots and tumor holoprotein according to an embodiment of the present invention;

FIG. 2 is an electrophoresis gel-running graph of a fluorescent field and Coomassie Brilliant blue of a mixture (QDs + BSA) of carbon quantum dot particles (QDs), Bovine Serum Albumin (BSA), a carbon quantum dot particle-modified BSA (QDs-BSA) inactivated vaccine, and carbon quantum dot particles and BSA, provided in Experimental example 1 of the present invention, under a 56 ℃ reaction condition;

FIG. 3 is a fluorescence emission spectrogram of the quantum dot and breast cancer 4T1 tumor holoprotein vaccine provided in Experimental example 2 of the present invention;

FIG. 4 is an electrophoresis gel-running graph of a mixture of carbon quantum dot particles (QDs), 4T1 breast cancer tumor digestive protein (W4T1), quantum dot modified whole-target protein (QDs-W4T1) vaccine, carbon quantum dot particles and 4T1 breast cancer tumor digestive protein (QDs + W4T1) provided in Experimental example 2 of the present invention under the reaction conditions of fluorescence field and Coomassie brilliant blue;

FIG. 5 is a graph showing a comparison of inguinal lymph of a mouse provided in Experimental example 3 of the present invention;

FIG. 6 is a graph showing the tumor growth curves of mice treated with the tumor immunoactivator injection and control mice according to Experimental example 3 of the present invention;

FIG. 7 is a tumor survival curve of mice treated with the tumor immunoactivator injection provided in Experimental example 3 of the present invention and mice of a control group.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.

The invention provides a quantum dot modified protein vaccine, which comprises raw materials of quantum dot particles and antigen protein, wherein the surfaces of the quantum dot particles comprise biocompatible functional groups, and the antigen protein and the functional groups act to enable the protein to be wound on the surfaces of the quantum dot particles through non-covalent bond.

Wherein the biocompatible functional group comprises one or more of hydroxyl, carboxyl, sulfhydryl and amino. According to the application, the antigen protein is modified through the quantum dots with the biocompatible functional groups, the antigen protein interacts with the functional groups, and the antigen protein is wound on the surfaces of the quantum dot particles through the non-covalent bond effect, so that the space conformation of the protein is changed, and the probability of specific recognition of the protein is enhanced. The quantum dot modified antigen protein greatly improves the immunogenicity of the protein, further has better immune activation characteristic, and can be applied to personalized immunotherapy of cancers.

In the application, the antigen protein is a full-target protein vaccine with immunogenicity; the term "whole-target protein vaccine" refers to a tumor protein vaccine that targets all specific antigens on a tumor.

Specifically, the antigen type of the full-target protein vaccine is selected from all proteins digested by tumor tissues or all proteins digested by tumor cell membranes; preferably, the antigen type of the whole target protein vaccine is selected from one or more of tumor tissue digestive protein, proliferation protein and tumor cell line differentiation protein.

In particular, for the purposes of this application, an antigenic protein is a whole protein vaccine extracted from tumor cells of an individual suffering from a tumor; preferably, the individual suffering from a tumor is a mammal; preferably, the mammal is a human; preferably, the mammal is a non-human mammal; preferably, the non-human mammal is selected from any one of mouse, rat, dog, pig, rabbit, cow, horse, sheep, monkey, and ape.

In a non-limiting illustrative example, antigenic proteins include, but are not limited to: bovine serum albumin vaccine or breast cancer 4T1 tumor holoprotein vaccine.

In addition, the application also provides a preparation method of the quantum dot modified protein vaccine, which comprises the following steps:

and S1, preparing the quantum dots.

The preparation method of the quantum dot particle comprises the following steps:

mixing and dissolving a precursor carbon source and a functional raw material in a solvent, heating and reacting for 2-10h at the temperature of 110-220 ℃, cleaning and carrying out solid-liquid separation, and drying a separated solid product;

preferably, the precursor carbon source comprises at least one of citric acid, glucose and polyethylene glycol; the functionalized raw material comprises at least one of urea, biuret and triurea. The quantum dot particles are synthesized by mixing a precursor carbon source and a functionalized raw material and performing heat treatment. Because the precursor carbon source has small molecular or ionic state and other sizes, the surface of the quantum dot can contain a biocompatible functional group by mixing with the functionalized raw material.

Preferably, in the application, the reaction system is cleaned by using an alcohol solution, and the separated solid product is washed by water and centrifugally separated at the rotating speed of 6000-10000 rpm; wherein the alcohol solution comprises methanol or ethanol.

It should be understood that the present application is not limited to the preparation of quantum dot particles by heating the above solvent at 110-220 deg.c, but the above raw materials can be prepared by other methods including, but not limited to, chemical oxidation, combustion, microwave synthesis, template method, etc., according to the process parameters required by the specific method.

And S2, modification.

Referring to fig. 1, the antigenic protein is modified with quantum dots containing biocompatible functional groups such that the protein is entangled to the surface of the quantum dot particles by non-covalent bonding.

Specifically, the modification comprises the steps of dissolving quantum dot particles in deionized water to prepare a solution with the concentration of 0.1-1.5mg/mL, mixing the solution of the quantum dot particles with antigen protein, and reacting for 1-30min at the temperature of 25-100 ℃; stirring at 40-250rpm during modification reaction, and purifying after reaction.

Wherein the mass ratio of the quantum dot particles to the antigen protein is 1: 0.10-10000.

The preparation method of the quantum dot modified protein vaccine is simple, the operation condition is mild, the active functional groups on the surfaces of the quantum dots are enabled to act with the antigen protein through thermal recombination, and the ultra-small quantum dots can modify the conformation structure of the protein again, so that the protein is wound on the surfaces of the quantum dots under the action of heat generated by external energy, and the protein vaccine combining the quantum dots and the tumor protein is formed. The spatial conformation of the antigen protein can be changed by modifying the quantum dots, and the conformational modifications lead to the remarkable enhancement of the immunogenicity of the normal protein and simultaneously cause the dysfunction of the immunosuppressive protein on cancer cells. The probability of specific recognition of the protein is enhanced. The quantum dot modified protein vaccine can greatly improve the immunogenicity of protein, further has better immune activation characteristic, and can be applied to personalized immunotherapy of cancers. The application also fully embodies that the quantum dots can be widely applied to the preparation of modified protein vaccines for tumor specific immune drugs.

The features and properties of the present invention are described in further detail below with reference to examples.

Example 1

The embodiment provides a quantum dot modified bovine serum albumin (CQDs-BSA) vaccine, and the preparation method comprises the following steps:

dissolving 2g of citric acid and 8g of urea in 30mL of DMSO solvent according to the mass ratio to obtain a transparent solution, placing the transparent solution in a 50mL of polytetrafluoroethylene high-pressure reaction kettle, reacting for 4 hours at 160 ℃, adding a large amount of ethanol into the reacted solution, washing to obtain a black solid, washing the solid with water, centrifuging (8000rpm, 5min), and drying to obtain dark blue powder. The diameter of the quantum dots obtained is measured to be 3-10 nm. The C, N, O, S element mass ratios of the quantum dots are 50.1%, 29.3%, 19.1% and 1.5%, respectively.

Dissolving the obtained quantum dots in deionized water, preparing a solution with the concentration of 0.1mg/mL, mixing the quantum dots and the bovine serum albumin according to the mass ratio of 1:10, heating to 56 ℃ by adopting an oven heating mode, reacting for 10min, and stirring at the rotating speed of 100 rpm. Thus obtaining the quantum dot modified bovine serum albumin (CQDs-BSA) vaccine.

Example 2

The embodiment provides a quantum dot modified breast cancer cell whole-target protein vaccine (CQDs-W4T1), and the preparation method comprises the following steps:

dissolving citric acid and biuret in water (or ultrapure water, PBS buffer solution, etc.) according to the mass ratio of 1:3 to obtain a transparent solution, placing the transparent solution in a 50ml polytetrafluoroethylene high-pressure reaction kettle, and reacting for 3h at 200 ℃. Adding a large amount of ethanol into the reacted solution to obtain black solid, washing the solid with water, centrifuging (8000rpm, 5min), and drying to obtain dark blue powder.

Dissolving the quantum dots in deionized water to prepare a solution with the concentration of 0.1mg/mL, and adding 1 × 10 per milliliter of the solution⁷4T1 mammary cancer tumor digestive protein (W4T 1). Heating to 56 deg.C by heating in water bath, reacting for 10min, and stirring at 100 rpm. Thus obtaining the quantum dot modified breast cancer cell whole target protein vaccine (CQDs-W4T 1).

Example 3

The embodiment provides a quantum dot modified tumor cell (QDs-cell) inactivated vaccine, and the preparation method comprises the following steps:

2g of citric acid and 6g of biuret are dissolved in 30ml of water (or ultrapure water, PBS buffer solution and the like) according to the mass ratio to obtain a transparent solution, the transparent solution is placed in a 50ml of polytetrafluoroethylene high-pressure reaction kettle, and the reaction is carried out for 3 hours at the temperature of 200 ℃. Adding a large amount of ethanol into the reacted solution to obtain black solid, washing the solid with water, centrifuging (8000rpm, 5min), and drying to obtain dark blue powder.

Dissolving the quantum dots in deionized water to prepare a solution with the concentration of 0.1mg/mL, and adding 1 × 10 per milliliter of the solution⁷4T1 breast cancer tumor cells. Heating to 56 deg.C with electric heating table, reacting for 10min while stirring at 100 rpm. Thus obtaining the quantum dot modified tumor cell (QDs-cell) inactivated vaccine.

Experimental example 1

The carbon quantum dot particles (QDs), Bovine Serum Albumin (BSA), the inactivated vaccine of carbon quantum dot particle-modified bovine serum albumin (QDs-BSA), and the mixture of carbon quantum dot particles and bovine serum albumin (QDs + BSA) obtained in example 1 were subjected to electrophoretic gel-casting, and the results are shown in fig. 2.

As can be seen from FIG. 2, the QDs-BSA obtained after complexation is shown in A of FIG. 2, which corresponds to an electrophoresis band on the protein, showing fluorescence, indicating effective bonding between the carbon dot and the protein. In FIG. 2B, it is shown that the proteins in BSA, QDs-BSA and QDs + BSA were stained.

Experimental example 2

The ultraviolet absorption spectrum and the fluorescence spectrum of the carbon quantum dot particles (QDs) and the quantum dot modified full-target protein (QDs-W4T1) vaccine obtained in example 2 are shown in fig. 3.

As can be seen from FIG. 3, the QDs-W4T1 obtained after recombination has an absorption spectrum at 719nm under 665nm excitation.

The mixture (QDs + W4T1) of the carbon quantum dot particles (QDs) obtained in example 2, 4T1 breast cancer tumor digestive protein (W4T1), quantum dot modified whole target protein (QDs-W4T1) vaccine, carbon quantum dot particles and 4T1 breast cancer tumor digestive protein was subjected to electrophoretic gel running, and the results are shown in fig. 4.

As can be seen from FIG. 4, the QDs-W4T1 obtained after complexing is shown in A of FIG. 4, corresponding to an electrophoresis band on the protein, showing fluorescence, indicating effective bonding of the carbon dot and the protein. In B of FIG. 4, it is shown that the proteins in W4T1, QDs-W4T1 and QDs + W4T1 are all stained.

Experimental example 3

Will be described in example 30.1mL of the obtained carbon quantum dot-enhanced inactivated vaccine (carbon quantum dot concentration of 0.2mg/mL, number of 4T1 cells of 1X 10)⁷Individual) were injected subcutaneously into balb/c mice. Four pairs of mammary glands were taken out at 0h, 4h, 24h and 48h, respectively, and imaged, and the mice were observed for lymph before injection and lymph at 4h, 24h and 48h after injection, and the results are shown in fig. 5.

As can be seen from FIG. 5, the inactivated vaccine of tumor cells (QDs-cells) modified by carbon quantum dot particles can increase the lymphatic presentation of antigen.

Experimental example 4

The carbon quantum dot particles were prepared as in example 1.

The tumors of two breast cancer mice (4T1 type and EMT6 type) are removed, digested and proliferated to obtain 4T1 holoprotein and EMT6 holoprotein.

Dissolving the obtained carbon quantum dot particles in deionized water to prepare a solution with the concentration of 0.1mg/mL, mixing the carbon quantum dot particles and digested cancer cell holoprotein (4T1 and EMT6) according to the mass ratio of 1.0:10, heating to 56 ℃ by adopting a hot plate heating mode, reacting for 10min, and stirring at the rotating speed of 100 rpm. Thereby obtaining the quantum dot modified full-target protein vaccines QDs-4T1 and QDs-EMT 6.

A certain amount of QDs-4T1 quantum dot modified full-target protein vaccine, QDs-EMT6, PBS and pure 4T1 tumor inactivated whole protein are injected into a 4T1 tumor mouse body. Preferably, the injection is metered to 200ul and the method of injection is one of intravenous injection, subcutaneous injection and ascites injection, preferably subcutaneous injection.

When the tumor volume of the mouse is larger than 1200mm³In time, mice were euthanized based on animal ethics and observed for tumor growth and survival curves.

Tumor growth curves of the mice were measured, and the results are shown in fig. 6. FIG. 6 shows that the tumor growth of the experimental group QDs-4T1 is significantly inhibited and cured, while the tumor growth of the control group QDs-EMT6, PBS and 4T1 inactivated protein is gradually increased. The quantum dot modified full-target protein vaccine QDs-4T1 is shown to activate the tumor immunity function of mice specifically, and inhibit and kill the tumors in the mice.

Survival curves of the mice were measured and the results are shown in fig. 7. FIG. 7 shows that the QDs-4T1 in the experimental group survived all day 60, while the QDs-EMT6, PBS, and 4T1 in the control group all died about 36 days. The quantum dot modified full-target protein vaccine QDs-4T1 is proved to cure the tumor in the mouse body specifically.

In summary, the quantum dot modified protein vaccine provided by the application acts with the protein vaccine through the active functional group on the surface of the quantum dot, and the ultra-small quantum dot can modify the conformation structure of the protein again, so that the protein is wound on the surface of the quantum dot under the action of heat generated by external energy, and the protein vaccine combining the quantum dot with the tumor protein is formed. The spatial conformations of the protein can be changed by modifying the protein through quantum dots, and the conformational modifications lead to the remarkable enhancement of the immunogenicity of normal proteins and simultaneously cause the dysfunction of immunosuppressive proteins on cancer cells. The probability of specific recognition of the protein is enhanced. The quantum dot modified protein vaccine can greatly improve the immunogenicity of protein, and further has better immune activation characteristic, and the preparation method is simple and the operation condition is mild. The obtained quantum dot modified protein vaccine can be applied to personalized immunotherapy of cancers.

The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.