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Tumor antigen loaded polydopamine nanoparticles, and preparation method and application thereof

A technology of tumor antigen and polydopamine, which is applied in antitumor drugs, cancer antigen components, vertebrate antigen components, etc., can solve the problems of high cytotoxicity and cell membrane damage, achieve good biocompatibility, and the preparation method is mild and simple , the effect of inhibiting growth

Active Publication Date: 2020-06-30
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

Cationic polymers, such as chitosan (CS) and polyethyleneimine (PEI), are effective in delivering antigens and eliciting immune responses, but may be highly cytotoxic due to the damage they cause to cell membranes
Therefore, the development of efficient, non-toxic biomaterials as antigen delivery systems remains a bottleneck

Method used

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  • Tumor antigen loaded polydopamine nanoparticles, and preparation method and application thereof
  • Tumor antigen loaded polydopamine nanoparticles, and preparation method and application thereof
  • Tumor antigen loaded polydopamine nanoparticles, and preparation method and application thereof

Examples

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preparation example Construction

[0039] The preparation method of polydopamine nanoparticles loaded with tumor antigens comprises steps:

[0040] Dissolve dopamine hydrochloride in deionized water to obtain a dopamine hydrochloride solution; add sodium hydroxide aqueous solution to the dopamine hydrochloride solution under stirring at 37-70°C to obtain the first mixed reaction system, the first mixed reaction The mass fraction of sodium hydroxide in the system is 0.0001% to 0.1%, followed by oxidation, rearrangement, and polymerization for 1 to 6 hours; the concentration of dopamine hydrochloride solution is 1 to 60 mg·mL -1 ;

[0041] Centrifuge the reaction product at 5,000 to 15,000 g for 3 to 25 minutes, and then wash to collect polydopamine nanoparticles; resuspend the polydopamine nanoparticles in deionized water to obtain a polydopamine nanoparticle solution;

[0042] The polydopamine nanoparticle solution is mixed with the tumor antigen solution, and reacted for 1 to 24 hours at 0 to 37° C.; wherein,...

Embodiment 1

[0047] Example 1: Preparation and application of polydopamine (OVA@PDA) nanoparticles loaded with tumor model antigen OVA

[0048] 1. Synthesis of OVA@PDA nanoparticles

[0049] 30 mg of dopamine hydrochloride was dissolved in 10 mL of deionized (DI) water, and an aqueous sodium hydroxide solution was added under stirring conditions at 45° C. to obtain the first mixed reaction system. The mass fraction of sodium hydroxide in the first mixed reaction system was 0.1%. , then reacted for 3 hours; the product obtained by the reaction was centrifuged at 7000×g for 10 minutes to collect polydopamine nanoparticles (PDA nanoparticles), and washed with deionized water to remove residual dopamine, and then the PDA nanoparticles were resuspended in 3 mL to remove In deionized water, a PDA nanoparticle solution was obtained.

[0050] 5mg OVA is dissolved in 5mL deionized water, then add 0.5mL PDA nanoparticle solution and formaldehyde aqueous solution under stirring condition at 30 ℃, ob...

Embodiment 2

[0070] Example 2: Preparation and application of polydopamine nanoparticles loaded with tumor cell lysates

[0071] 1. Preparation of tumor cell lysate (TCL)

[0072] Add complete medium (RPMI1640 containing 10% FBS and 1% antibiotics) to MC-38 cells in 5% CO 2 Incubate at 37°C in an incubator. When the cells reached 80%-90% confluence, the cells were routinely digested to prepare a cell density of 1×10 7 mL -1 cell suspension. 2 mL of the cell suspension was subjected to five freeze-thaw cycles for lysis, followed by centrifugation of the lysate to remove cell debris (1500 g, 10 min). The concentration of TCL solution was measured by BCA method, and the obtained TCL was diluted to a suitable concentration for in vivo and in vitro experiments.

[0073] 2. Synthesis of PDA nanoparticles and TCL@PDA nanoparticles

[0074] 20 mg of dopamine hydrochloride was dissolved in 10 mL of deionized water, and then an aqueous solution of sodium hydroxide was added under vigorous stir...

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Abstract

The invention relates to a tumor antigen loaded polydopamine nanoparticle, and a preparation method and an application thereof. The tumor antigen loaded polydopamine nanoparticle is prepared by covalently connecting a tumor antigen to the surface of a polydopamine nanoparticle through Michael addition and Schiff base reaction, wherein the tumor antigen comprises, but is not limited to, one or moreselected from the group consisting of a specific tumor antigen peptide fragment, a tumor cell lysate, a specific tumor antigen DNA fragment and an adjuvant CpG. The tumor antigen loaded polydopaminenanoparticle prepared by using the method provided by the invention has good biocompatibility, can effectively activate in-vivo anti-tumor immunity, significantly inhibits the growth of tumor cells, can improve the tumor immunosuppressive microenvironment, further enhances the anti-tumor activity of the human body, can be used for immune treatment of tumors, and is simple and pollution-free in preparation method.

Description

technical field [0001] The invention relates to the technical field of biomaterials, in particular to polydopamine nanoparticles loaded with tumor antigens and a preparation method and application thereof. Background technique [0002] About 8.8 million people die from malignant tumors in the world every year, and 14 million new cases occur. The latest statistics show that in the past two decades, the cancer mortality rate in China has increased by nearly 30%, and one out of every four or five deaths is due to cancer, ranking among the top three causes of death. Although surgery, radiotherapy and chemotherapy are used clinically to treat malignant tumors, many patients still experience postoperative recurrence and cannot tolerate the toxic and side effects of radiotherapy and chemotherapy. Emerging tumor immunotherapy brings hope to patients with advanced tumors, but the current clinical benefits are not obvious. [0003] There are two main obstacles in tumor immunotherapy...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/59A61K39/00A61P35/00
CPCA61K47/6935A61K47/59A61K39/0011A61P35/00Y02A50/30
Inventor 张海玲冷希岗王晓莉王宁杨影
Owner INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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