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A kind of preparation method of targeted nuclear magnetic contrast agent

A nuclear magnetic contrast agent and targeting technology, which is applied in the field of functional modification of nanoparticles, can solve the problem of increasing active targeting, and achieve the effects of good stability, excellent targeting and long cycle effect

Inactive Publication Date: 2016-04-06
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Moreover, the surface of unmodified magnetic nanoparticles has no functional groups and is easily oxidized by oxygen in the air, which limits the application of magnetic nanoparticles, so the surface must be modified with a suitable surface modifier to prevent Reunite, improve its biocompatibility, endow magnetic particles with functional groups, and increase their active targeting functions

Method used

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  • A kind of preparation method of targeted nuclear magnetic contrast agent
  • A kind of preparation method of targeted nuclear magnetic contrast agent
  • A kind of preparation method of targeted nuclear magnetic contrast agent

Examples

Experimental program
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Effect test

Embodiment 1

[0049] Example 1Fe 3 o 4 Preparation of nanoparticles

[0050] Weigh 4.73gFeCl 3 ·6H 2 O and 2.78g FeSO 4 ·7H 2 O powder was dissolved in 100 mL of distilled water, stirred vigorously with a mechanical stirrer, and then 30 mL of ammonia water with a mass fraction of 25% was slowly added dropwise under nitrogen protection, and the pH was maintained at 10. The obtained precipitate is matured at 80°C, split and purified to obtain Fe 3 o 4 magnetic nanoparticles.

[0051] The magnetic nanoparticles prepared by the method are spherical in TEM observation, the average hydrated particle size is about 100nm, and the saturation magnetization is about 70emu / g.

Embodiment 2

[0052] Example 2: A targeted nuclear magnetic contrast agent, that is, CS-coated Fe 3 o 4 Preparation method of composite magnetic nanoparticles

[0053] 40mL (1mg / mL) Fe 3 o 4 Nanoparticles were gradually added dropwise into 100mL (2mg / mL) CS solution, and 50mL of absolute ethanol and 200μL of cross-linking agent GA were gradually added dropwise. After 4 hours of reaction, 0.2g of sodium borohydride was added as a reducing agent. After dialysis, CS packets were obtained. Covered Fe 3 o 4 Nanoparticle solution;

[0054] The composite magnetic nanoparticles prepared by this method are spherical in TEM observation, the average hydrated particle size is about 190nm, and the saturation magnetization is about 52emu / g.

Embodiment 3

[0055] Embodiment 3: A kind of targeted nuclear magnetic contrast agent is FA-PEG-CS coated Fe 3 o 4 Preparation method of composite magnetic nanoparticles.

[0056] Weigh 5mg of FA and dissolve it in 10mL of DMSO, add cross-linking agent 5mg of DCC, 5mg of NHS to activate under nitrogen protection for 12h, use a 0.22um organic filter membrane to remove the precipitate; then accurately weigh 10mg of NHS 2 -PEG-COOH was dissolved in the activated FA DMSO solution, reacted under nitrogen protection for 6h, added acetone to centrifuge to remove the precipitate, and finally dialyzed to obtain the FA-PEG-COOH complex, which was freeze-dried for use.

[0057] B. Then, 40mL (1mg / mL) Fe 3 o 4 Nanoparticles were gradually added dropwise into 100mL (3mg / mL) CS solution, 50mL of absolute ethanol and 200μL of cross-linking agent GA were gradually added dropwise, and after 4 hours of reaction, 0.2g of sodium borohydride was added as a reducing agent, and CS package was obtained after di...

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Abstract

The invention discloses a targeted nuclear magnetism contrast agent and a preparation method thereof. The contrast agent is ferroferric oxide (Fe3O4) composite magnetic nanoparticles coated with chitosan (CS) modified by folic acid (FA) grafted with amine-PEG-carboxyl (NH2-PEG-COOH). The method comprises the steps: under an environment of a DMSO solvent, activated FA and NH2-PEG-COOH are subjected to dicyclohexylcarbodiimide (DCC) crosslinking, dialysis and freeze-drying, and an FA-PEG-COOH compound is obtained; then the FA-PEG-COOH compound is added into a solution containing Fe3O4 coated with CS, crosslinking and dialysis are carrying out, and the functionalized Fe3O4 composite magnetic nanoparticles coated with FA-PEG-CS are obtained, wherein crosslinking agents are 1-(3-dimethyl aminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxy succinimide (NHS). The multifunctional composite magnetic nanoparticle preparation is spherical-like in shape, has the particle size distributed between 100 and 250 nm in a water environment, has the electric potential of +20 mV, and has good stability, strong targeting property, and excellent image enhancement effect.

Description

technical field [0001] The present invention relates to the functional modification of nanoparticles, in particular to a superparamagnetic Fe 3 o 4 Surface functional modification and preparation method thereof. Background technique [0002] As a natural polysaccharide, CS has the advantages of good biocompatibility, low toxicity, degradability, and no allergic reaction. 3 o 4 After wrapping, its biocompatibility and stability can be effectively improved. In addition, Fe 3 o 4 It is a superparamagnetic material with the ability to image under MRI and generate heat under alternating magnetic field. Using Fe 3 o 4 As a magnetic induction hyperthermia medium, magnetic fluid can monitor tumor volume in real time without other detection methods. Chitosan-modified magnetic Fe 3 o 4 As a new generation of water-soluble magnetic fluid, nanoparticles have a large number of amino active groups on the surface, which can be connected with many ligands, antibodies, and drugs, ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/12
Inventor 侯振清周水帆贾梦梦侯鲁谢黎崖
Owner XIAMEN UNIV
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