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Gold-gadolinium hybrid dendrimer compound, preparation and application thereof

A dendrimer and complex technology, which can be used in medical preparations without active ingredients, medical preparations containing active ingredients, and drug combinations, which can solve problems such as reports of PD-1siRNA complexes that have not yet been found.

Pending Publication Date: 2021-03-12
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] According to the domestic and foreign literature search results, there are no related reports on the preparation of gold-gadolinium hybrid dendrimer PD-1 siRNA complex and its application in anti-T cell exhaustion and immunotherapy.

Method used

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  • Gold-gadolinium hybrid dendrimer compound, preparation and application thereof
  • Gold-gadolinium hybrid dendrimer compound, preparation and application thereof
  • Gold-gadolinium hybrid dendrimer compound, preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0097] (1) Weigh 20 mg of DOTA-NHS and 60 mg of the fifth generation PAMAM dendrimer (G5.NH 2 ) (purchased from Dendritech, USA), were dissolved in 5mL dimethyl sulfoxide (DMSO) and 20mL DMSO respectively, and DOTA-NHS (purchased from CheMatech, France) solution was added to G5.NH 2 In the solution, the reaction was stirred in a water bath at 30° C. for 24 hours. After the reaction, use a cellulose dialysis bag with a molecular weight cut-off of 8000-14000 to dialyze in pure water (3L) for 3 days (change the water 3-4 times a day) and freeze-dry to obtain G5.NH 2 - DOTA powder;

[0098] (2) Weigh 60mg of G5.NH 2 -DOTA powder was dissolved in 20mL of ultrapure water, 2.7mg of 1,3-PS (purchased from Shanghai Bailingwei Technology Co., Ltd.) was added, stirred and reacted in a water bath at 30°C for 24 hours, and the main component G5.NH was obtained 2 - Aqueous solution of DOTA-PS. Subsequently, the G5.NH 2 -The DOTA-PS solution was stirred in an ice bath, and 634 μL of HAu...

Embodiment 2

[0101] To the G5.NH prepared in embodiment 1 step (1) 2 -DOTA for characterization:

[0102] Weigh 10mg of G5.NH respectively 2 and G5.NH 2 -DOTA was fully dissolved in 5mL ultrapure water, then in G5.NH 2 and G5.NH 2 - Add 50 μL of triethylamine to the DOTA solution, stir at room temperature for 30 minutes, then add 29 μL of acetic anhydride and stir at room temperature for 24 hours. After the reaction, use a cellulose dialysis bag with a molecular weight cut-off of 8,000 to 14,000 to dialyze in pure water (3 L) for 3 days (change the water 3-4 times a day), freeze-dry to obtain acetylated G5.NHAc and G5. NHAc-DOTA powder. Weigh 2-3 mg of G5.NHAc and G5.NHAc-DOTA powder, add 600 μL of deuterated water (D 2 O) carry out 1 H NMR test. Such as figure 2 As shown in A, through the methyl proton peak of the acetyl group at 1.89ppm, each G5.NH 2 The number of DOTA connected online is 10.4.

Embodiment 3

[0104] The Gd Au DENP-PS prepared in step (2) of Example 1 and related intermediate products in the preparation process were characterized.

[0105] (1) get the G5.NH in embodiment 1 step (2) 2 -Appropriate amount of DOTA-PS solution, using a cellulose dialysis bag with a molecular weight cut-off of 8,000 to 14,000, dialyzed in pure water (3L) for 3 days (changing water 3-4 times a day), freeze-dried to obtain G5.NH 2 -DOTA-PS powder. Weigh 3-4 mg and add to 600 μL of D 2 O, carry on 1 H NMR test. Such as figure 2 As shown in B, the proton peak at 2.25-3.4ppm represents G5.NH 2 The methylene proton peak of 1.93ppm is the methylene proton peak of 1,3-PS, indicating the successful grafting of 1,3-PS, and the integral calculation can get each G5.NH 2 There are 9.1 1,3-PS connections.

[0106] (2) Weigh G5.NH 2 - DOTA and Gd Au DENP-PS powders were prepared into 0.2mg / mL aqueous solution respectively, and tested by ultraviolet-visible spectroscopy (UV-vis). Such as imag...

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Abstract

The invention relates to a gold-gadolinium hybrid dendrimer compound, preparation and application thereof, wherein the compound is a compound of gold-gadolinium hybrid dendrimers and PD-1 siRNA (smallinterfering ribonucleic acid). According to the invention, the method is simple in operation process, mild in reaction condition and easy to purify, and the used synthetic raw materials are environment-friendly materials, so that the method has an industrial implementation prospect.

Description

technical field [0001] The invention belongs to the field of functional diagnosis and treatment integrated hybrid nanomaterials and its preparation and application, in particular to a gold-gadolinium hybrid dendrimer complex and its preparation and application. Background technique [0002] In recent years, immunotherapy has gradually developed into the fourth major tumor treatment method after surgery, radiotherapy and chemotherapy. Different from traditional treatment methods, immunotherapy activates the human immune system, relies on its own immune function to kill cancer cells and tumor tissues, and performs precise immune killing. It has high specificity, low toxicity, and immune memory killing effect, so it has gradually become a The focus of current cancer research. In the process of tumor immunity, T cell-mediated immune response and tumor rejection play a central role, but the normal function of T cells is greatly limited due to the exhaustion of T cells under norm...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/59A61K47/54A61K31/713A61K48/00A61K49/04A61K49/12A61K49/10A61P35/00A61P37/04C12N15/87
CPCA61K47/595A61K47/545A61K47/543A61K31/713A61K49/04A61K49/124A61K49/106A61P35/00A61P37/04C12N15/87C07K14/70521
Inventor 史向阳高悦欧阳智俊杨超宋聪沈明武
Owner DONGHUA UNIV
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