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Preparation method for ferroferric oxide nano particle targeted MRI contrast agent

A technology of ferric oxide and nanoparticles, applied in preparations for in vivo tests, pharmaceutical formulations, etc., can solve the problems of no iron oxide nanoparticles, etc., achieve good water solubility, easy operation, and efficient targeting sexual effect

Inactive Publication Date: 2013-12-04
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] Searching domestic and foreign literature and patents, there is no report that the surface of PEI-coated iron oxide nanoparticles prepared by one-step hydrothermal synthesis is further modified with HA of different molecular weights and used for targeted MRI studies of tumor models in vivo

Method used

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  • Preparation method for ferroferric oxide nano particle targeted MRI contrast agent
  • Preparation method for ferroferric oxide nano particle targeted MRI contrast agent
  • Preparation method for ferroferric oxide nano particle targeted MRI contrast agent

Examples

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Embodiment 1

[0065] 1.26g FeCl 2 4H 2 Pour O into a beaker, add 7.75mL of ultrapure water, and add 6.25mL of NH 3 ·H 2 O, the above mixed solution was continuously stirred for 10-15 minutes under the air atmosphere, so that the ferrous iron was fully oxidized, and then the mixed solution was transferred to a high-pressure reactor. 0.52g PEI was ultrasonically dissolved in 5mL aqueous solution, transferred to the reactor with a pipette gun, fully mixed with the solution in the reactor, and reacted at 134°C for 3 hours. After the reaction was over, it was naturally cooled to room temperature, and the obtained black precipitate Fe 3 o 4 -PEI magnetic separation to remove the supernatant, add an appropriate amount of ultrapure water to ultrasonically disperse, and then magnetically separate, repeat the ultrapure water washing five times to remove impurities, and then redisperse in 20mL ultrapure water to obtain PEI coating Fe 3 o 4 Nanoparticles (Fe 3 o 4 -PEI).

[0066] Take the pre...

Embodiment 2

[0069] HA with different molecular weights (Mw=5805, 23.5mg; Mw=31200, 124.8mg) were dissolved in 5mL ultrapure water at 70°C, and then 5mL containing EDC (7.7mg) and NHS (4.6mg) were added to it. DMSO solution. After the solution was mixed evenly, it was stirred and activated for 3h. Then the activated HA solution was added dropwise to 4 mL of Fe prepared in Example 1. 3 o 4 -in PEI-FI solution, stirred and reacted for three days, then washed with ultrapure water magnetic separation, and redispersed in 5mL ultrapure water to obtain HA-modified Fe with different molecular weights 3 o 4 Aqueous solutions of nanoparticles (respectively defined as Fe 3 o 4 -PEI-FI-HA 6K and Fe 3 o 4 -PEI-FI-HA 31K ).

[0070] Take Fe 3 o 4 -PEI-FI (Example 1), Fe 3 o 4 -PEI-FI-HA 6K and Fe 3 o 4 -PEI-FI-HA 31K 0.5 mL each of the aqueous solution was vacuum freeze-dried, and then the three materials were subjected to thermogravimetric analysis (e.g. figure 2 shown). Depend on ...

Embodiment 3

[0072] Take Fe respectively 3 o 4 -PEI-FI (Example 1), Fe 3 o 4 -PEI-FI-HA 6K and Fe 3 o 4 -PEI-FI-HA 31K (Example 2) Each 0.1mL aqueous solution was prepared with ultrapure water to prepare 1.5mL aqueous solutions for measuring surface potential (as in Table 1) and hydrodynamic diameter (as in image 3 ). Potentiometric results showed that Fe 3 o 4 -The surface potential of PEI-FI nanoparticles reached +26.1mV. After modification, the obtained Fe 3 o 4 -PEI-FI-HA 6K and Fe 3 o 4 -PEI-FI-HA 31K The surface potential of the nanoparticles decreased to -16.3mV and -21.9mV, respectively.

[0073] The results further proved that HA was successfully modified to the surface of nanoparticles. Subsequently, we measured the prepared Fe 3 o 4 -PEI-FI-HA 6K and Fe 3 o 4 -PEI-FI-HA 31K The hydrodynamic diameter of nanoparticles at different storage times was used to evaluate their colloidal stability, such as image 3 shown. Fe 3 o 4 -PEI-FI-HA 6K and Fe 3 o 4...

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Abstract

The invention relates to a preparation method for a ferroferric oxide nano particle targeted MRI contrast agent. The method comprises the following steps: 1, utilizing a hydrothermal method to synthesize PEI coated Fe3O4 nano particles Fe3O4-PE1; 2, conducting surface modification on fluorescein isothiocyanate FI by the Fe3O4-PE1 nano particles; 3, connecting hyaluronic acids of different molecular weights with surfaces of the nano particles to obtain the ferroferric oxide nano particle targeted MRI contrast agent. The method has the advantages of mild reaction conditions, simple operation process, and easiness in separating and purification. The prepared Fe3O4 magnetic nano particles have good colloid stability, biocompatibility and tumor targeting, and underlying application value in the field of in-vivo tumor targeted MRI diagnoses.

Description

technical field [0001] The invention belongs to the field of preparation of nuclear magnetic resonance imaging (MRI) contrast agents, and in particular relates to a preparation method of iron ferric oxide nanoparticles targeted MRI contrast agents. Background technique [0002] Superparamagnetic iron oxide (Fe 3 o 4 ) has unique magnetic properties, strong signal, low dosage and good biocompatibility, making it a good contrast agent in MRI diagnostic applications. Fe 3 o 4 Nanoparticles can shorten the transverse relaxation time of water protons, thereby enhancing the contrast and sensitivity of MRI. However, it should be pointed out that in order to successfully integrate Fe 3 o 4 When nanoparticles are used in biomedical imaging diagnosis, it is necessary to ensure their good stability and biocompatibility in vitro and in vivo. Therefore, the synthesis of multifunctional Fe with good water solubility and colloidal stability 3 o 4 Nanoparticles have become the focu...

Claims

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Application Information

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IPC IPC(8): A61K49/12
Inventor 沈明武李静超孙文杰史向阳
Owner DONGHUA UNIV
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