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Efficient targeting nanovaccine vector, preparation method thereof, targeting nanovaccine and preparation method thereof

A nano-vaccine and targeting technology, applied in medical preparations with non-active ingredients, medical preparations containing active ingredients, pharmaceutical formulas, etc., can solve problems such as inability to generate cellular immune responses, and improve antigen cross-presentation , Improve endocytosis efficiency, high-efficiency activation effect

Active Publication Date: 2020-06-19
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, tumor antigens are usually taken up by antigen-presenting cells (APCs) in the form of exogenous antigens through endocytosis, and further degraded and processed in the acidic environment of endosomes or lysosomes. Presented to CD4+ T cells, mainly induce humoral immune response, unable to generate effective cellular immune response

Method used

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Examples

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Effect test

preparation example Construction

[0046] The present invention also provides a method for preparing an efficient targeting nano-vaccine carrier, comprising the following steps:

[0047] A) activating the arginine double-protected by p-toluenesulfonyl and tert-butoxycarbonyl, then adding an aqueous solution of linear poly-α-lysine for reaction, dialyzing and lyophilizing the reacted solution to obtain a lyophilized product;

[0048] The molar ratio of the linear poly-alpha-lysine to p-toluenesulfonyl and tert-butoxycarbonyl double-protected arginine is 1: (10-100);

[0049] B) reacting the lyophilized product in the step A) with trifluoroacetic acid, adding anhydrous ether for sedimentation, vacuum drying and dialysis to obtain a cationic polymer;

[0050] C) Mix N,N'-diisopropylethylamine, activated mannose, and the cationic polymer in step B) to react, and the reacted product is dialyzed and freeze-dried to obtain highly efficient targeting nano vaccine vector;

[0051] The mannose is activated according to...

Embodiment 1

[0099] The preparation of embodiment 1 PLL-RT

[0100] Linear poly-α-lysine (molecular weight 15,000 Da) was dissolved in deionized water, and p-toluenesulfonyl and tert-butoxycarbonyl double-protected arginine was dissolved in DMF. Then, add EDC·HCl and HOBT, activate the reaction at room temperature for 1 hour, then slowly add the aqueous solution of PLL, and react at room temperature for 72 hours. After dialysis and freeze-drying, the product was reacted under the condition of trifluoroacetic acid for 4 hours, added with anhydrous ether to settle, vacuum-dried, dialyzed, and freeze-dried to obtain the white solid product PLL-RT.

[0101] The molar ratio of poly-α-lysine grafted to tosyl-protected arginine (Arg(Tos)) was 1:90.

Embodiment 2

[0102] Example 2 Preparation of Targeted Vaccine Vector Man-PLL-RT

[0103] Dissolve mannose in 1 mL of NaOH (1M), stir for 30 minutes, then add 1 mL of chloroacetic acid aqueous solution, and react at 60°C for 12 hours. Add 250 μL of hydrochloric acid (1M) to adjust the pH value to 2.5 to carboxylate the reacted mannose. The product was activated for 30 minutes by adding EDC·HCl and HOBT aqueous solution. Then add PLL-RT and DIPEA, stir and react at 30°C for 48 hours, obtain Man-PLL-RT after dialysis and lyophilization.

[0104] The grafting molar ratios of PLL-RT to mannose were 1:5, 1:10 and 1:15, respectively.

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Abstract

The invention provides an efficient targeting nanovaccine vector. The efficient targeting nanovaccine vector comprises a linear poly(alpha-lysine); the linear poly(alpha-lysine) is grafted with mannose and arginine protected by p-toluenesulfonyl, wherein a molar ratio of the linear poly(alpha-lysine) to the arginine protected by the p-toluenesulfonyl is 1:(10-100), and a molar ratio of the linearpoly(alpha-lysine) to the mannose is 1:(1-30). According to the invention, electropositive Man-PLL-RT molecules are used as the targeting vaccine vector to support an electronegative antigen and an adjuvant, and the targeting vaccine vector can effectively improve endocytosis efficiency of the antigen and the adjuvant in BMDCs, and meanwhile, can efficiently activate the BMDCs, improve the cross-presentation effect of the antigen and activate in-vivo immunoreaction. The invention further provides a preparation method of the efficient targeting nanovaccine vector, a targeting nanovaccine and apreparation method of the targeting nanovaccine.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials, and in particular relates to a high-efficiency targeting nano vaccine carrier, a preparation method thereof, a targeting nano vaccine and a preparation method thereof. Background technique [0002] Malignant tumors are one of the main killers that threaten human health and life, and their morbidity, mortality, and rejuvenation are increasing year by year. At present, the clinical treatment methods for cancer are mainly surgery, radiotherapy and chemotherapy. However, none of these traditional treatment methods can completely eliminate tumor cells and effectively control the metastasis and recurrence of tumor cells. In recent years, tumor immunotherapy was rated as the first of the top ten scientific breakthroughs in 2013 by [Science], opening a new chapter in tumor immunotherapy. [0003] Inducing a specific anti-tumor immune response is the key to tumor immunotherapy. [See Mellma...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/34A61K39/39A61K39/00A61P35/00
CPCA61K39/0011A61K39/39A61K47/34A61K2039/55561A61P35/00
Inventor 田华雨陈杰方华攀徐彩娜郭兆培林琳陈学思
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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