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CT contrast agent with gold nanoparticles wrapped with zwitter-ion modified dendrimer and preparation method and application of CT contrast agent

A technology of dendritic macromolecules and gold nanoparticles, which is applied in the preparation of X-ray contrast agents, material analysis using wave/particle radiation, and material analysis, can solve problems such as no discovery, and achieve easy operation, simple synthesis process, The Effect of Good CT Imaging Function

Inactive Publication Date: 2017-03-22
DONGHUA UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] Searching the literature at home and abroad, there is no relevant report on the preparation of gold nanoparticle CT contrast agent coated with zwitterion-modified polyamidoamine dendrimers and its application in vitro and in vivo

Method used

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  • CT contrast agent with gold nanoparticles wrapped with zwitter-ion modified dendrimer and preparation method and application of CT contrast agent
  • CT contrast agent with gold nanoparticles wrapped with zwitter-ion modified dendrimer and preparation method and application of CT contrast agent
  • CT contrast agent with gold nanoparticles wrapped with zwitter-ion modified dendrimer and preparation method and application of CT contrast agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] Using 10mL of anhydrous propanol as a solvent, β-propiolactone (2.97g) and N-[(3-dimethyl)propyl]acrylamide (DMAPA, 4.62g) were mixed under anhydrous and oxygen-free conditions at 0°C The mixture was stirred and reacted for 3 hours, filtered with suction, washed with anhydrous acetone three times, 5 mL each time, and vacuum-dried to obtain carboxybetaine acrylamide white powder (CBAA).

[0075] Weigh 10 mg of the fifth-generation PAMAM dendrimer and 16.9 mg of CBAA, dissolve them in 5 mL of methanol and 5 mL of NaCl solution (0.138 M), and use BHT as a polymerization inhibitor (0.05 mg, dissolved in 0.5 mL Methanol), after each is completely dissolved, put together and stir for 3 days to obtain the medium product PAMAM.NH 2 -CBAA 20 . Dialyze with a dialysis bag with a molecular weight cut-off of 1000 for three days (dialyze in PBS buffer for one day, change the solution 3 times; dialyze in distilled water for 2 days, change the water 6 times), freeze-dry to obtain dr...

Embodiment 2

[0080] Weigh respectively CBAA, {(Au 0 ) 100 -PAMAM.NH 2 -CBAA 20}, {(Au 0 ) 100 -PAMAM.NH 2 -CBAA 80} and {(Au 0 ) 100 -PAMAM.NHAc-mPEG 20} each 5mg, respectively dissolved in 500μL D 2 O, carry out hydrogen spectrum analysis (as attached figure 2 shown). figure 2 (a) is the hydrogen spectrum of CBAA. It can be seen from the figure that the obtained CBAA substance is very pure without redundant peaks. figure 2 (b) is {(Au 0 ) 100 -PAMAM.NH 2 -CBAA 20}, the characteristic peak of CBAA appeared at 1.89ppm, and it was integrated that 20.11 CBAA molecules were loaded on each G5 on average. figure 2 (c) is {(Au 0 ) 100 -PAMAM.NH 2 -CBAA 80}, the characteristic peak of CBAA appeared at 1.89ppm, and it was integrated that each G5 was loaded with 80.21 CBAA molecules on average. figure 2 (d) is {(Au 0 ) 100 -PAMAM.NH Ac -mPEG 20}, the characteristic peak of PEG appeared at 3.2ppm, and it was integrated that 17.9 mPEG molecules were loaded on each G5 on averag...

Embodiment 3

[0082] Take by weighing respectively in embodiment 1: {(Au 0 ) 100 -PAMAM.NHAc-CBAA 20}, {(Au 0 ) 100 -PAMAM.NHAc-CBAA 80} and {(Au 0 ) 100 -PAMAM.NHAc-mPEG 20} each 0.5 mg, respectively dissolved in 1 mL of ultrapure water for potential particle size testing (as shown in Table 1). {(Au 0 ) 100 -PAMAM.NHAc-CBAA 20}, {(Au 0 ) 100 -PAMAM.NHAc-CBAA 80} and {(Au 0 ) 100 -PAMAM.NHAc-mPEG 20}The hydrated particle diameters are 140.0nm, 138.2nm, and 109.2nm, respectively. Due to the modification of zwitterions, a thick hydration layer will be formed on the surface of the particles, so {(Au 0 ) 100 -PAMAM.NHAc-CBAA 20}, {(Au 0 ) 100 -PAMAM.NHAc-CBAA 80} has a hydrated particle size larger than that of {(Au 0 ) 100 -PAMAM.NHAc-mPEG 20}, but the amount of zwitterionic modification does not have much effect on the average hydration layer thickness of the particles. {(Au 0 ) 100 -PAMAM.NHAc-CBAA 20}, {(Au 0 ) 100 -PAMAM.NHAc-CBAA 80} and {(Au 0 ) 100 -PAMA...

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Abstract

The invention relates to a CT contrast agent with gold nanoparticles wrapped with zwitter-ion modified dendrimer and a preparation method and application of the CT contrast agent. The surface of the dendrimer is modified with the zwitter-ion carboxybetaine acrylic amide (CBAA), and the gold nanoparticles are wrapped with the dendrimer, wherein the dendrimer is fifth-generation polyimide dendrimer G5.NH2. The preparation method comprises the steps that the CBAA and the fifth-generation polyimide are stirred and reacted at the room temperature to obtain CBAA-G5.NH2, an HAuCl4 solution is added, NaBH4 is added for reduction, triethylamine and acetic anhydride are added finally, and then the CT contrast agent is obtained. Compared with a traditional contrast agent modified by mPEG, the consuming quantity of in-vitro macrophages is low, protein adsorption in the protein adsorption resistance experiment is low, the in-vivo rat blood circulation time is longer, liver gathering in the mouse CT experiment is low, the renal metabolism is slower, and the CT contrast agent can also be used for rat blood pool radiography and rabbit lymphonodus VT imaging.

Description

technical field [0001] The invention belongs to the field of CT contrast agent and its preparation and application, in particular to a zwitterion-modified dendrimer-wrapped gold nanoparticle CT contrast agent and its preparation and application. Background technique [0002] Cancer is an abnormal lesion formed by the body under the action of various carcinogenic factors, the cells of local tissues lose the normal regulation of their growth at the gene level, resulting in abnormal clonal proliferation. The latest "Global Cancer Report 2014" released by the International Cancer Research Center under the World Health Organization pointed out that half of the new cancer cases occurred in Asia, most of which came from China, and the number of new cancer cases in China ranked first in the world. Cancer is becoming a major threat to human health and survival worldwide. In view of the local invasion and distant metastasis characteristics of malignant tumors, the treatment effect an...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/04G01N23/04
CPCA61K49/04G01N23/046
Inventor 史向阳熊智娟夏进东王玥
Owner DONGHUA UNIV
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