Method for preparing high magnetic resonance sensitivity ferroferric oxide nano-particle with tumor-targeting function

A ferroferric oxide and tumor targeting technology, which is applied in the fields of polymer chemistry and biomedical engineering, can solve the problems of lack of focus site specificity and limited application of nanoparticles, and achieve the tumor targeting function of magnetic resonance imaging sensitivity, Effects of prolonging survival and reducing side effects

Inactive Publication Date: 2009-06-03
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

It is worth mentioning that the nanoparticles prepared by the methods reported in the above literatures lack specificity to the lesion site, which limits their application in vivo.

Method used

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  • Method for preparing high magnetic resonance sensitivity ferroferric oxide nano-particle with tumor-targeting function
  • Method for preparing high magnetic resonance sensitivity ferroferric oxide nano-particle with tumor-targeting function
  • Method for preparing high magnetic resonance sensitivity ferroferric oxide nano-particle with tumor-targeting function

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Experimental program
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Embodiment 1

[0036] Preparation of folate-PEG-PCL or folate-PEG-PLA carrier material folate-PEG-PCL or folate-PEG-PLA for tumor dual-targeting nanomicelles modified by folic acid

[0037] 1) Synthesis of allyl-polyethylene glycol-polycaprolactone (ally-PEG-PCL)

[0038] Synthesis of diblock copolymers using anionic ring-opening polymers of ethylene oxide (EO) and caprolactone (ε-CL). Add 0.48g of naphthalene to the three-neck flask, dry it in vacuum at room temperature for 12h, add about 20mL of freshly steamed THF, stir evenly with a magnetic force, add excess potassium, and stir for 0.5h to prepare potassium naphthalene reagent. Add 0.25 mL of allyl alcohol and potassium naphthalene reagent to the two-neck flask, stir magnetically for 0.5 h, add 1.0 g of 18-crown-6 ether THF solution that has been vacuum-dried at 36°C for 12 h, and stir for 0.5 h. Under the condition of an ice-salt bath, about 25 mL of dry ethylene oxide was passed through, and the reaction was stirred at room temperatu...

Embodiment 2

[0048] 1) α-hydroxy-ω-amino polyethylene glycol (HO-PEG-NH 2 )Synthesis

[0049]Add 1g of naphthalene to the three-necked flask, vacuum dry at room temperature for 24h, quickly add 20mL of dry THF, stir until the naphthalene is dissolved, quickly add 1g of fresh metal potassium, stir for 0.5h, and the solution turns dark green; weigh 0.7g (5.73 mmol) 18-crown-6 ether was added to a 100mL three-necked flask, vacuum-dried at about 40°C for 24 hours, and then dissolved in 20mL of dry THF; In the there-necked flask filled with ethanolamine, stir for 0.5h, the reaction color turns dark red, quickly transfer the THF solution of potassium naphthalene and ethanolamine into the there-necked flask filled with 18-crown-6 ether, stir for 0.5h (all operations are in under the protection of argon).

[0050] Place the reaction bottle containing the initiator in an ice-salt bath, and pass through it for 1 h under the protection of argon for 3 Ethylene oxide dried by molecular sieves, the ...

Embodiment 3

[0060] Synthesis of Lipophilic Superparamagnetic Iron Tetroxide

[0061] Add Fe(acac) rapidly under anhydrous, oxygen-free and nitrogen protection conditions 3 (2mmol), 1,2-Hexadecandiol (10mmol), oleic acid (6mmol), oleylamine (6mmol) and 20mL benzyl ether, magnetically stirred evenly. Under magnetic stirring and nitrogen protection, the temperature was rapidly raised to 200° C. in a sand bath, and the heating was continued for 2 hours after the temperature stabilized. Then, the temperature was rapidly raised to the reflux state (the temperature of the external bath was about 300° C.), and the reflux was continued for 1 hour. After the reaction, the reaction system was removed from the heat source, and cooled to room temperature under nitrogen protection.

[0062] Under atmospheric atmosphere and magnetic stirring conditions, add the black product into absolute ethanol with a volume ratio of about 3 to 4 times, stir evenly, and centrifuge at 10000r / min for 5min. The black ...

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Abstract

The invention discloses a method for preparing high magnetic resonance sensitivity ferroferric oxide nano-particle with tumor-targeting function. Amphiphilic block polymer of the end capping of tumor-targeted ligand and super-paramagnetic ferroferric oxide are dissolved in tetrahydrofuran, then the obtained solution is added into ionized water or distilled water, the tetrahydrofuran is volatilized, the super-paramagnetic ferroferric in the solution is separated out, washed by the distilled water, then dispersed into the ionized water or the distilled water, and finally centrifugalized, thus the nano-particle is obtained; the tumor-targeted ligand is folic acid, polypeptide or antibody. In the invention, by loading lipophilic ferroferric oxide nano-particle at self-assembled micellar inner core, the tumor-targeted and water-soluble ferroferric oxide nano-particle that is below 50 nm is developed. The tumor-targeting function is realized by coupling the folic acid or antibody at micellar surface. The invention has wide application prospect.

Description

technical field [0001] The invention relates to a preparation method of iron ferric oxide nanoparticles, in particular to a preparation method of iron ferric oxide nanoparticles with tumor targeting function, high sensitivity of magnetic resonance imaging, and small diameter iron ferric oxide nanoparticles, which belongs to polymer chemistry and biomedical engineering. Background technique [0002] Magnetic resonance imaging (MRI) is a very important diagnostic technique in clinical medicine. In recent years, researchers have paid more and more efforts to improve its resolution and contrast quality. Targeted delivery of contrast reagents to the target site is a very important method, which can not only improve the contrast effect but also reduce the negative effects and toxicity. Magnetic resonance techniques are especially useful for detecting early signs of disease. Superparamagnetic iron oxide or super paramagnetic iron oxide (SPIO) is a new type of contrast agent for m...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/12A61K49/16
Inventor 帅心涛苑仁旭洪国斌梁碧玲
Owner SUN YAT SEN UNIV
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