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A preparation method of hyaluronic acid modified superparamagnetic iron oxide/gold composite nanoprobe

A hyaluronic acid-modified, superparamagnetic technology, which can be used in preparations for in vivo experiments, pharmaceutical formulations, preparation of X-ray contrast agents, etc., and can solve the problem of not finding superparamagnetic iron oxide/gold nanocomposite probes. , to achieve good colloidal stability, good biocompatibility, and easy operation.

Inactive Publication Date: 2018-05-15
DONGHUA UNIV +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] Searching domestic and foreign literatures, there is no discovery about the preparation of HA-modified superparamagnetic iron oxide / gold nanocomposite probes by modified "co-precipitation" method for targeted MR / CT dual-modality imaging of cancer cells in vitro and tumor models in vivo Research related reports

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  • A preparation method of hyaluronic acid modified superparamagnetic iron oxide/gold composite nanoprobe
  • A preparation method of hyaluronic acid modified superparamagnetic iron oxide/gold composite nanoprobe
  • A preparation method of hyaluronic acid modified superparamagnetic iron oxide/gold composite nanoprobe

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Embodiment 1

[0068] 5.4mL HAuCl 4 4H 2 O solution (30mg / mL) was added to 50mL PEI (100mg) aqueous solution, stirred for 30 minutes; then, 0.9mL NaBH treated with ice bath was added to the mixture 4 (45.4mg) solution (ethanol / ultrapure water, v / v=1:2), continue to stir in ice bath for 1-2h; ), freeze-dried to obtain Au-PEI nanoparticle powder, which was stored at -20°C for future use.

[0069] Dissolve the Au-PEI powder prepared above in 10 mL of water, then add to 10 mL of FeCl 2 4H 2 O (0.089g) and FeCl 3 ·6H 2 In the aqueous solution mixed with O (0.157g), heat and stir at 50°C for 3-5 minutes to fully dissolve it; then, add 5mL NaOH (1.0g) aqueous solution dropwise to the mixed solution, and stir at 80°C for 30 minutes; React at room temperature for 1-2 hours; after the reaction, the product is magnetically separated, washed and purified to obtain PEI-modified Fe 3 o 4 / Au nanoparticles, stored at 4°C for later use; 3mL nanoparticle solution was taken, vacuum freeze-dried for X-...

Embodiment 2

[0071] With the 10mL Fe in embodiment 1 3 o 4 / Au-PEI (25mg) aqueous solution was magnetically separated and dispersed into 10mL DMSO solution; then HA (Mw=5808, 9mg) was dissolved in 5mL of water at 70°C, and 5mL containing EDC (2.98mg) and NHS (1.79 mg) in DMSO solution, stir and activate for 2-4h; then add the activated HA to the above Fe 3 o 4 / Au-PEI in DMSO solution, stirred for 2 to 4 days, magnetically separated, washed and dispersed in water to obtain Fe 3 o 4 / Au-HA composite nanoprobes. Take 3mL nanoparticle solution, vacuum freeze-dry for thermogravimetric analysis. The TGA results show that the HA upload is about 2.81% (see attached figure 2 ).

Embodiment 3

[0073] Get the Fe prepared by the present invention 3 o 4 / Au-PEI (Example 1) and Fe 3 o 4 / Au-HA (Example 2) suspension 100 μL, respectively prepared 1.5 mL aqueous solution with ultrapure water for measuring surface potential and hydrodynamic diameter (see attached table 1). The potential results showed that the surface potentials of nanoparticles before and after HA modification were +36.1mV and -19.6mV, and the hydrodynamic particle sizes dispersed in water were 339.3nm and 342.2nm, respectively.

[0074] Get the Fe prepared by the present invention 3 o 4 5 μL of each aqueous solution of Au-HA composite nanoprobe (Example 2), and then prepare 100 μL of nanoparticle suspensions with ultrapure water. And take 5 μL of nanoparticle suspension and drop it on the surface of the copper grid, dry it in the air and use it for TEM test (see attached image 3 ). The TEM test results show that the morphology of the ferric oxide nanoparticles in the composite nanoparticles is sp...

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Abstract

The present invention relates to a preparation method of hyaluronic acid-modified superparamagnetic iron oxide / gold composite nanoprobe, the NaBH4 reduction method is used to prepare polyethyleneimine PEI-coated Au nanoparticles; through the modified "co-precipitation" method , "one-step" synthesis of Fe3O4 / Au‑PEI composite nanoparticles; then, HA was modified on its surface to prepare Fe3O4 / Au‑HA composite nanoprobes. The invention has simple process, mild reaction conditions and easy operation; the prepared Fe3O4 / Au-HA composite nanoprobe has high relaxation rate, good X-ray attenuation ability, good colloidal stability and biocompatibility, and specific The ability to target tumor cells with high CD44 receptor expression has potential application value in the field of tumor-targeted MR / CT dual-modal imaging diagnosis in vivo.

Description

technical field [0001] The invention belongs to the field of preparation of contrast agents for magnetic resonance and CT imaging, in particular to a preparation method of hyaluronic acid-modified superparamagnetic iron oxide / gold composite nanoprobes. Background technique [0002] In recent years, ferric oxide / gold composite nanoparticles have received more and more attention in the field of biomedicine, especially as contrast agents for MR and CT dual-modal imaging, which can effectively overcome the limitations of single-modal imaging advantages and disadvantages, and improve the accuracy of disease diagnosis. Our research group has prepared Fe3O4 / gold composite nanoparticles through layer-by-layer self-assembly method and simple hydrothermal method, and explored the feasibility of its MR / CT diagnostic application (patent number: ZL201310170267.0; Cai et al. J. Mater. Chem., 2012, 22, 15110-15120. Patent No.: ZL201310072165.5; Li et al. ACS Appl. Mater. Interfaces 2013, ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/04A61K49/12A61K49/18
Inventor 沈明武胡勇丁玲杨嘉张贵祥史向阳
Owner DONGHUA UNIV
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