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Dendritic macromolecule coated gold nanoparticle composite material as well as preparation and application thereof

A technology of amine dendrimer and composite material, applied in the field of nano-gold particle composite material wrapped by dendrimer, can solve problems such as undiscovered application, and achieve the effects of simple operation process, mild reaction conditions and easy purification

Pending Publication Date: 2022-03-01
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Searching domestic and foreign literature and patents has not found any preparation methods for targeting molecularly modified polyamide-amine dendrimers encapsulating nano-gold particles loaded with CpG nanocomposites and its application in PET / CT imaging and tumor immunotherapy

Method used

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  • Dendritic macromolecule coated gold nanoparticle composite material as well as preparation and application thereof
  • Dendritic macromolecule coated gold nanoparticle composite material as well as preparation and application thereof
  • Dendritic macromolecule coated gold nanoparticle composite material as well as preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0077] (1) Weigh 20mg of DOTA-NHS and 60mg of the fifth-generation PAMAM dendrimer (G5), dissolve them in 5mL dimethyl sulfoxide (DMSO) and 20mL DMSO respectively, add the DOTA-NHS solution to the G5 solution , 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 three days (change the water 3-4 times a day) and then freeze-dry to obtain G5-DOTA dry powder;

[0078] (2) Weigh 4.3mg of glucosamine (DG) and 40mg of polyethylene glycol (Mw=2000, MAL-PEG-COOH), dissolve them in 2mL ultrapure water and 5mL ultrapure water respectively, and dissolve them in lithium chloride (Licl) and triethylamine (Et3N) under the catalysis of Michael addition reaction occurred mixing and stirring reaction for 24h. After the reaction, use a cellulose dialysis bag with a molecular weight cut-off of 500 to dialyze in pure water (3L) for three days (change the water 3-4 times a da...

Embodiment 2

[0084] (1) Characterize the G5-DOTA prepared in step (1) of Example 1:

[0085] Weigh G5-DOTA and fully dissolve it in 5 mL ultrapure water, then add 50 μL triethylamine to the solution, stir at room temperature for 30 minutes, then add 29 μL 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 three days (change the water 3-4 times a day) and freeze-dry to obtain acetylated G5-DOTA powder. Weigh 2-3 mg of G5.NHAc-DOTA powder, add 500 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, the number of DOTA connected to each G5 is calculated to be 8.2 by the difference method.

[0086] (2) The polyethylene glycol (DG-PEG-COOH) prepared in embodiment 1 step (2) is characterized:

[0087] Weigh 2-3 mg of DG-PEG-COOH powder, add 500 μL of deute...

Embodiment 3

[0091] To {(Au prepared in Example 1 0 ) 100 -G5-DOTA-(DG-PEG)} for characterization.

[0092] Weigh {(Au 0 ) 100 -G5-DOTA-(DG-PEG)} and {(Au 0 ) 100 -G5-DOTA-PEG} powder, respectively configured into 0.2 mg / mL aqueous solution, for ultraviolet-visible spectroscopy (UV-vis) test. Such as image 3 As shown, {Au 0 ) 100 -G5-DOTA-PEG} and {(Au 0 ) 100 -G5-DOTA-(DG-PEG)} has an obvious absorption peak around 520nm, which is the plasmonic resonance peak of Au nanoparticles, indicating the successful synthesis of Au nanoparticles.

[0093] Weigh {(Au 0 ) 100 -G5-DOTA-(DG-PEG)} and {(Au 0 ) 100 -G5-DOTA-PEG} powders were formulated into 2mg / mL aqueous solution, dropped on the ultra-thin carbon film, dried and tested by transmission electron microscope (TEM). Such as Figure 4 As shown in A-D, {(Au 0 ) 100 -G5-DOTA-(DG-PEG)} and {(Au 0 ) 100 -G5-DOTA-PEG} has good monodispersity, and the size of gold nanoparticles wrapped inside is uniform, about 2.0nm.

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Abstract

The invention relates to a dendrimer-coated gold nanoparticle composite material and preparation and application thereof, a fifth-generation polyamide-amine dendrimer is used as a carrier, chelating and targeting molecules are modified on the surface of the carrier, then gold nanoparticles are coated by an in-situ reduction synthesis method, and finally CpG is loaded to obtain the dendrimer-coated gold nanoparticle composite material. The preparation process is short in period, the material is low in toxicity under the use dosage and good in biocompatibility, PET / CT bimodal imaging can be achieved, the anti-tumor immune response can be achieved, and potential clinical application value is achieved.

Description

technical field [0001] The invention belongs to the field of functional nano-materials, in particular to a nano-gold particle composite material wrapped by dendritic macromolecules and its preparation and application. Background technique [0002] Nowadays, cancer has become one of the main factors threatening human health. According to statistics, the incidence of cancer is increasing year by year, and the mortality rate of cancer patients has also remained high. In view of the local invasion and distant metastasis characteristics of malignant tumors, the treatment effect and cost of cancer are closely related to the period when the cancer is discovered. Early detection and early treatment are the most practical ways to reduce cancer mortality. In recent decades, with the development of nanoscience and technology, various nanosystems have begun to be used in the early diagnosis and treatment of cancer. [0003] In the process of clinical diagnosis, molecular imaging play...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K51/06A61P35/00A61K49/10C08G73/02A61K103/00
CPCA61K51/06A61P35/00A61K49/106C08G73/028
Inventor 曹雪雁李才史向阳
Owner DONGHUA UNIV
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