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Preparation method and application of RGD-modified ultra-small magnetic iron oxide nanoparticles

An iron oxide nanometer and ultra-small magnetic technology, which is applied in the field of biomedical nanomaterials, can solve the problems of unfavorable nanoparticle surface ligand replacement reaction, complicated nanoparticle surface modification, and expensive reducing agent, so as to save preparation time and improve Excellent magnetic properties and monodispersity

Active Publication Date: 2015-01-07
SOUTHEAST UNIV
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Problems solved by technology

[0013] In previous studies, the reaction of preparing magnetic iron oxide nanoparticles by high-temperature pyrolysis often used oleic acid and oleylamine as surfactants, 1,2-hexadecanediol or 1,2-dodecanediol Alcohol is used as the complex reaction system of the reducing agent, but these reducing agents are relatively expensive, the cost is high, and it is not convenient for mass production
At the same time, the simultaneous use of oleylamine and oleic acid as surfactants will make the surface modification of nanoparticles more complicated, which is not conducive to the subsequent ligand replacement reaction on the surface of nanoparticles.

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  • Preparation method and application of RGD-modified ultra-small magnetic iron oxide nanoparticles

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preparation example Construction

[0070] A preparation method of RGD-modified ultra-small magnetic iron oxide nanoparticles, comprising the steps of:

[0071] Step 1. Preparation of Ultra-Small Magnetic Iron Oxide Nanoparticles

[0072] It is prepared by an improved high temperature pyrolysis method, and the reaction device is as follows figure 1 As shown, the reaction preparation process is as follows figure 2 As shown, wherein, iron acetylacetonate is a reaction raw material and a precursor, oleylamine is a surfactant and a reducing agent, and dibenzyl ether is a solvent. The specific preparation process is as follows:

[0073] Mix dibenzyl ether and oleylamine at a volume ratio of 1:9 to 9:1, continuously feed nitrogen to remove oxygen in the system, and then add iron acetylacetonate, the concentration of iron acetylacetonate in the reaction solution system is 0.125 to 0.175mol / L, heated at 2-6°C / min to 190-230°C (the temperature is the nucleation temperature of nanoparticles), preferably 220°C, and kep...

Embodiment 1

[0094] Preparation of ultrasmall magnetic iron oxide nanoparticles under different growth times.

[0095]Add 8mL of dibenzyl ether and 12mL of oleylamine to three 100mL three-necked flasks, continue to feed nitrogen to remove the oxygen in the system, then add 3mmol of iron acetylacetonate, and use the temperature control device at 3.3°C / min Heating rate Heat each reaction system to 220°C (nucleation temperature) and keep the temperature for 1h. This stage is the nucleation stage of magnetic iron oxide nanoparticles. During this process, the solution turns from brownish red to bright black. Next, each reaction system was heated to 290° C. (growth temperature) at a heating rate of 3.3° C. / min, and each reaction system was maintained at this temperature for 45 min, 35 min, and 15 min, respectively, so as to realize the preparation of nanoparticles with different growth times. After the reaction is over, remove the heat source, transfer the reactant to a beaker after naturally co...

Embodiment 2

[0097] Preparation of ultra-small magnetic iron oxide nanoparticles under different volume ratios of reaction materials.

[0098] Add 2mL dibenzyl ether and 18mL oleylamine, 8mL dibenzyl ether and 12mL oleylamine, 18mL dibenzyl ether and 2mL oleylamine respectively in three 100mL three-necked flasks, continuously feed nitrogen to remove the oxygen in the system, and then Add 3mmol of iron acetylacetonate, heat each reaction system to 220°C (nucleation temperature) at a heating rate of 3.3°C / min through a temperature program control device, and keep the temperature for 1h. This stage is the nucleation of magnetic iron oxide nanoparticles stage, during which the solution turns from brown-red to bright black. Next, each reaction system was heated to 290° C. (growth temperature) at a heating rate of 3.3° C. / min, and each reaction system was maintained at this temperature for 15 minutes to realize the preparation of nanoparticles under different volume ratios of reaction raw materi...

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Abstract

The invention discloses a preparation method of RGD-modified ultra-small magnetic iron oxide nanoparticles. The preparation method comprises the following steps: preparing ultra-small magnetic iron oxide nanoparticles by taking ferric acetylacetonate as a reaction raw material and a precursor, taking oleylamine as a surfactant and a reducing agent and taking dibenzyl ether as a solvent; replacing oleylamine molecules wrapped on the surfaces of the nanoparticles by utilizing dopamine-modified HOOC-PEG-COOH to realize PEG-modification of the surfaces of the nanoparticles; and finally, chemically coupling RGD cyclic peptide by virtue of free carboxyl at the tail end of the PEG to obtain the RGD-modified ultra-small magnetic iron oxide nanoparticles. The method of synthesizing the ultra-small magnetic iron oxide nanoparticles has the characteristics of a simple process, a high raw material conversion ratio, strong repeatability and the like. The synthesized magnetic iron oxide nanoparticles have the characteristics of a regular morphology, an ultra-small dimension, good stability, good monodispersity, high biocompatibility, and tumor specific targeting, and the like, and can be used as a T1-weighted imaging high-performance magnetic resonance imaging contrast agent with a tumor active targeting function.

Description

technical field [0001] The invention relates to the technical field of biomedical nanomaterials, in particular to a method for preparing RGD-modified ultra-small magnetic iron oxide nanoparticles. Background technique [0002] Magnetic iron oxide nanoparticles have a very important impact in the field of biomedicine, especially in magnetic resonance imaging and molecular imaging technology, which has great potential application value. As we all know, the clinical diagnosis and treatment of tumors requires the establishment of early diagnosis methods for small tumors, and the development of relevant technical methods to obtain individualized information at the molecular and physiological levels has become the key to solving this problem. At present, the development of tumor molecular imaging technology still strongly depends on the development of molecular imaging probe technology. With its unique physical properties and good biological safety, magnetic iron oxide nanoparticl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/18A61K49/08
Inventor 张宇贾正阳谢俊宋丽娜顾宁
Owner SOUTHEAST UNIV
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