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Preparation method of folic acid-modified multifunctional targeting contrast agent magnetic iron oxide/gold nanoparticles

A technology targeting contrast agents and magnetic iron oxides, applied in preparations for in vivo tests, pharmaceutical formulations, emulsion delivery, etc.

Inactive Publication Date: 2014-10-15
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] Retrieve related MRI / CT targeted dual-modality contrast agent Fe at home and abroad 3 o 4 / Au-FA nanoparticles literature and patent results show that by regulating multifunctional targeting Fe 3 o 4 Au / Fe of Au-FA nanoparticles 3 o 4 There is no relevant report on the research on optimizing the effect of MRI / CT dual-modality imaging.

Method used

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  • Preparation method of folic acid-modified multifunctional targeting contrast agent magnetic iron oxide/gold nanoparticles
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  • Preparation method of folic acid-modified multifunctional targeting contrast agent magnetic iron oxide/gold nanoparticles

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Embodiment 1

[0070] (1) First synthesize Fe by co-precipitation method 3 o 4 Nanoparticles, prepare 1M sodium hydroxide 250mL, under the protection of nitrogen, preheat to 80 ° in advance, and then FeCl 2 4H 2 O and FeCl 3 ·6H 2 O was dissolved in 0.4M dilute hydrochloric acid (25mL) at a molar ratio of 2:1, the air was removed, and then added to the preheated NaOH solution, and stirred and reacted for 2 hours under the protection of nitrogen; after the reaction, naturally cooled to room temperature , after washing and separating the black precipitate, Fe 3 o 4 nanoparticles;

[0071] (2) Use the fifth generation polyamide / amine dendrimers (G5.NH 2 ) as the initial material, first 1.87mg of folic acid and 8.11mg of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDC) were dissolved in 2mL of dimethylsulfoxide (dimethylsulfoxide , DMSO), after stirring and activating for 3h, add G5.NH dropwise 2 Solution (22.00mg dissolved in 8mL DMSO), stirred for 3 days, the product...

Embodiment 2

[0077] Fe in the comparative example 3 o 4 / Au and Fe prepared by the present invention 3 o 4 / Au-FA nanomaterials are dispersed in aqueous solution, and the content of Fe and Au elements in the solution is measured by ICP-AES test method, and then the concentration of Fe is prepared by EP tube to be 0.002, 0.005, 0.01, 0.02, 0.05, 0.1 and 0.2mM aqueous solution 2mL, through T 2 Magnetic resonance imaging and CT imaging studies of different Au / Fe 3 o 4 molar ratio of Fe 3 o 4 / Au and Fe 3 o 4 T of / Au-FA 2 Relaxation and CT effects. The results showed that Fe 3 o 4 / Au and Fe 3 o 4 The relaxation rate of / Au-FA has a good linear relationship with the increase of iron concentration in the iron concentration range of 0-0.2mM. Reference attached Figure 4 and 5 , it can be seen from the linear relationship diagram that Au / Fe 3 o 4 Fe with a molar ratio of 0.2 3 o 4 / Au nanoparticles R 2 Relaxation rate 127.86mM -1 the s -1 , while Au / Fe 3 o 4 Fe with mol...

Embodiment 3

[0080] Take 0.1mL comparative example Fe 3 o 4 / Au ([Fe]=0.054mol / L, [Au]=0.029mol / L) and 0.08mL Fe prepared by the present invention 3 o 4 / Au-FA ([Fe]=0.061mol / L, [Au]=0.041mol / L) nanoparticles were prepared into a 1.5mL aqueous solution with ultrapure water, and then used to measure the hydrodynamic particle size. Such as Figure 7 The hydrodynamic particle size distribution shows that the Fe in the comparative example 3 o 4 / Au and Fe prepared by the present invention 3 o 4 / Au-FA nanomaterials are dispersed and stable in the water phase, and their hydrodynamic particle sizes are 418.3nm and 532.5nm, respectively, compared with the previously synthesized Fe 3 o 4 Hydrodynamic particle size of Au nanoparticles (200 nm, Cai, H.; Li, K.; Shen, M.; Wen, S.; Luo, Y.; Peng, C.; Zhang, G.; Shi, X .Facile assembly of Fe 3 o 4 Au nanocomposite particles for dual mode magnetic resonance and computed tomography imaging applications. Journal of Materials Chemistry, 2012, 22...

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Abstract

The invention relates to a preparation method of folic acid modified multifunctional targeted contrast agent magnetic iron oxide / gold nanoparticles. The method comprises the following steps: synthesizing Fe3O4 nanoparticles, and entrapping nanogold particles in a targeted molecular folic acid modified dendrimer to obtain {(Au<0>)50-G5.NH2-FA}DENPs; forming a high-molecular multilayer film on the surface of each of the Fe3O4 nanoparticles, and carrying out assembly modification of the outermost layer of the multilayer film by {(Au<0>)50-G5.NH2-FA}DENPs; carrying out shell layer cross-linking to obtain composite nanoparticles Fe3O4 / Au-FA; and adjusting the Au / Fe3O4 mole ratio of the Fe3O4 / Au-FA nanomaterial, optimizing the bimodal imaging effect, and carrying out acetylation modification to obtain an Fe3O4 / Au-FA nanomaterial having a best bimodal imaging effect. The method has the advantages of simple process, mild reaction conditions, and easy operation and separation.

Description

technical field [0001] The invention belongs to the field of preparation of contrast agent materials, in particular to a preparation method of folic acid-modified multifunctional targeting contrast agent magnetic iron oxide / gold nanoparticles. Background technique [0002] In recent years, with the development of nanotechnology, the emerging field of nanomedicine has received widespread attention and great research interest, such as cell separation, drug delivery, targeted diagnosis and treatment of tumors, molecular surgery, Medical imaging and nanorobots, etc. The early diagnosis and treatment of tumors is an important topic that countries all over the world focus on. It is becoming more and more important to apply nanoscience and technology to develop molecular imaging and in vivo imaging technology with high accuracy for early diagnosis of tumors. Common molecular imaging methods include X-ray computed tomography imaging (CT) and magnetic resonance imaging (Magnetic Re...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/18A61K49/12
Inventor 史向阳蔡红东李静超沈明武
Owner DONGHUA UNIV
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