A method for modifying the surface of ferroferric oxide nanoparticles and uses thereof

Abstract

The application discloses a method for functionalizing and modifying the surface of ferroferric oxide nanoparticles based on surfactants. Iron salt is dispersed in a high-boiling organic solvent to decompose, and ferroferric oxide nanoparticles are obtained by precipitation through a polar organic liquid. The average particle size of the ferroferric oxide nanoparticles is about 25 nm. The ferroferric oxide nanoparticles are emulsified and modified by surfactants, and then are surface-functionalized and modified by organic acids and alcohols to obtain carboxylated water-soluble ferroferric oxide nanoparticles which can be connected with molecules such as fluorescent groups, proteins, DNA, viruses and the like, and the average particle size is about 115 nm. The application has potential application value in the fields of optics, biomedical science, environmental science, materials, catalysis, energy and magnetic storage, and the preparation method is simple and easy to implement, and is suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of materials technology, and specifically relates to the surface modification and functionalization of iron oxide nanoparticles. Background Technology

[0002] Magnetic nanoparticles have broad application prospects in optics, biomedicine, environmental science, materials, catalysis, energy, and magnetic storage due to their advantages such as multifunctionality, tunability, and stability. Their advantages in the biomedical field are mainly reflected in the following aspects: (1) Tunableness: The performance of magnetic nanoparticles can be significantly regulated by changing their size, shape, morphology, and composition; (2) Superparamagnetism: The enrichment of nanoparticles can be regulated using an external magnetic field, thus providing possibilities for cell labeling, separation, and targeted drug delivery; (3) Good surface modification potential: Different surface modification methods can endow magnetic nanoparticles with different multifunctionalities to meet their different application needs in biomedicine and other fields; (4) Good stability and biocompatibility: Surface modification can prevent the aggregation of magnetic nanoparticles, thereby improving their biocompatibility.

[0003] Existing research has yielded some surface modifications to magnetic nanoparticles, but problems such as low modification efficiency, high cost, and poor specificity still exist. Therefore, developing efficient and inexpensive methods for surface functionalization modification of magnetic nanoparticles is of great significance in both science and engineering. Summary of the Invention

[0004] The purpose of this invention is to provide a method for surface functionalization modification of iron oxide (Fe3O4) nanoparticles. On one hand, the surface-modified monodisperse iron oxide nanoparticles have a size of 30 nm and exhibit good water solubility. On the other hand, carboxylated iron oxide nanoparticles have a size of 115 nm and can undergo multifunctional surface modification, such as connecting to the near-infrared II fluorescent molecule indocyanine green. Therefore, by utilizing the intrinsic magnetic order of iron oxide nanoparticles and the modification with near-infrared II fluorescent molecules, these magnetic nanoparticles have significant potential application value in the fields of magnetic resonance imaging and near-infrared II fluorescence imaging.

[0005] The iron oxide nanoparticles in this invention are obtained by reacting an iron precursor in a high-boiling-point organic solvent. Emulsification modification is performed using a surfactant, followed by surface functionalization using organic acids and alcohols, resulting in functionalized iron oxide nanoparticles capable of stably linking near-infrared II fluorescent molecules.

[0006] The method for preparing surface-functionalized iron oxide nanoparticles provided by this invention includes the following steps:

[0007] 1) Preparation of iron oxide nanoparticles;

[0008] 2) Preparation of water-soluble iron oxide nanoparticles;

[0009] 3) Preparation of surface-functionalized iron oxide nanoparticles.

[0010] Step 1) Ferric oleate is the preferred iron source, but other iron sources can also be used, such as ferric stearate, ferric acetylacetone, etc.

[0011] Step 1) The reaction process is usually carried out under a high-temperature protective atmosphere, with a temperature of 280-350 degrees Celsius, for example 300 degrees Celsius, a time of 0.5-3 hours, for example 1 hour, and an inert gas atmosphere, such as high-purity argon or high-purity nitrogen.

[0012] Step 2) Disperse the prepared iron oxide nanoparticles in an aqueous solution containing a surfactant. The surfactant can be selected from cetyltrimethylammonium bromide, cetyltrimethylammonium chloride, dodecyltrimethylammonium bromide, dodecyltrimethylammonium chloride, etc.

[0013] Step 2) Continue stirring the mixture at a temperature of 40-100 degrees Celsius, for example, 50 degrees Celsius, for 2-6 hours, for example, 3 hours. The reaction is usually carried out under a protective atmosphere, precipitation is usually carried out at room temperature, and polar alcohols such as ethanol and isopropanol are used as washing solvents.

[0014] Step 3) Use organic acids and alcohols, such as acrylic acid and ethylene glycol, to perform surface carboxylation modification on water-soluble iron oxide nanoparticles, usually at room temperature.

[0015] Step 3) Carboxylated iron oxide nanoparticles are activated using sodium N-hydroxysulfonate succinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and then linked with the near-infrared II fluorescent molecule indocyanine green. The reaction time is 8-24 hours, for example, 16 hours.

[0016] The present invention further provides fluorescence luminescence performance testing of the above-mentioned iron oxide nanoparticles, further clarifying their potential applications in the biomedical field. Attached Figure Description

[0017] Figure 1 The image shows a transmission electron microscope image of the iron oxide nanoparticles prepared in Example 1.

[0018] Figure 2 The image shows the X-ray diffraction pattern of the iron oxide nanoparticles prepared in Example 1.

[0019] Figure 3 Transmission electron microscope image of water-soluble iron oxide nanoparticles prepared in Example 2.

[0020] Figure 4 The image shows the dynamic light scattering pattern of the surface-carboxylated iron oxide nanoparticles prepared in Example 3.

[0021] Figure 5 The dynamic light scattering pattern of the surface-functionalized iron oxide nanoparticles prepared in Example 3.

[0022] Figure 6 The images show fluorescence detection patterns of different iron oxide nanoparticles prepared in Examples 1, 2, and 3.

[0023] Figure 7 The surface potential detection diagrams are for different iron oxide nanoparticles prepared in Examples 1, 2, and 3.

[0024] Figure 8 Fourier transform infrared spectra of different iron oxide nanoparticles prepared in Examples 2 and 3. Detailed Implementation

[0025] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions in the embodiments of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0026] Example 1

[0027] Preparation of iron oxide nanoparticles:

[0028] 10.8 g of ferric chloride hexahydrate and 36.5 g of sodium oleate were dissolved in 80 mL of ethanol, 60 mL of water, and 140 mL of n-hexane. The system was heated to 70°C and held at this temperature for 4 hours. The product was extracted three times to obtain ferric oleate. 3.6 g of the obtained ferric oleate was dissolved in 640 μL of oleic acid and 20 mL of octadecene. The system was heated to 120°C and held at this temperature for 30 minutes under an argon atmosphere. The temperature was then further increased to 320°C and held for 30 minutes. After the system cooled to room temperature, 60 mL of anhydrous ethanol and 15 mL of n-hexane were added, and the mixture was centrifuged at 8000 rpm for 3 minutes to obtain monodisperse iron(III) oxide nanoparticles.

[0029] like Figure 1 As shown, transmission electron microscopy images characterize the size and morphology of the iron oxide nanoparticles.

[0030] like Figure 2As shown, the position and intensity of the diffraction peaks revealed by X-ray diffraction analysis are well matched with those of iron(III) oxide (JCPDS19-0629), indicating that the material prepared by the above method is a homogeneous iron(III) oxide material.

[0031] Example 2

[0032] 150 mg of iron(III) oxide nanoparticles were dispersed in 3 mL of chloroform, and 150 mg of dodecyltrimethylammonium bromide was dissolved in 10 mL of water. The mixture was then sonicated for 10 minutes. The reaction mixture was subsequently heated to 70°C and held at this temperature for 4 hours under an argon atmosphere. After cooling to room temperature, 60 mL of anhydrous ethanol was added, and the mixture was centrifuged at 8000 rpm for 3 minutes to obtain water-soluble iron(III) oxide nanoparticles.

[0033] like Figure 3 As shown, transmission electron microscopy images characterize the size and morphology of water-soluble iron oxide nanoparticles.

[0034] Example 3

[0035] 50 mg of water-soluble iron oxide nanoparticles, 0.9 g of polyacrylic acid, and 11.1 g of ethylene glycol were mixed at room temperature for 1 hour. The product was washed with water. The product was activated with 3 mg of sodium N-hydroxysulfonate succinimide and 3 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and stirred at room temperature for 4 hours. Then, 0.3 mg of amino-indocyanine green was added, and the mixture was stirred at room temperature for 24 hours. 20 mL of water was added, and the mixture was centrifuged at 8000 rpm for 3 minutes to obtain surface-functionalized iron oxide nanoparticles.

[0036] like Figure 4 As shown, the dynamic light scattering pattern characterizes the size of the surface-carboxylated iron oxide nanoparticles.

[0037] like Figure 5 As shown, the dynamic light scattering pattern characterizes the size of the surface-functionalized iron oxide nanoparticles.

[0038] like Figure 6 As shown, the fluorescence detection pattern characterizes the luminescence of different iron oxide nanoparticles, indicating that indocyanine green was successfully attached to the surface of carboxylated iron oxide nanoparticles.

[0039] like Figure 7As shown, the surface potential detection diagram characterizes the surface potential changes of different iron oxide nanoparticles. The iron oxide nanoparticles in Example 1 have a positive surface potential. After carboxylation modification, the iron oxide nanoparticles in Example 2 have a negative surface potential. Subsequently, after linking indocyanine green molecules, the surface potential of the surface-functionalized iron oxide nanoparticles increased. This indicates that indocyanine green was successfully linked to the surface of the carboxylated iron oxide nanoparticles.

[0040] like Figure 8 As shown, Fourier transform infrared spectroscopy (FTIR) analysis revealed the variations in functional groups among different iron oxide nanoparticles. The presence of amide bonds in the surface-functionalized iron oxide nanoparticles indicates that indocyanine green was successfully attached to the surface of the carboxylated iron oxide nanoparticles.

[0041] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. An application of a method for surface modification of iron oxide nanoparticles, characterized in that, Surface-functionalized iron oxide nanoparticles were activated using sodium N-hydroxysulfonate succinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and then linked to near-infrared II fluorescent molecules indocyanine green, proteins, viruses, or DNA. The preparation method of the surface-functionalized iron oxide nanoparticles includes the following steps: 1) Preparation of iron oxide nanoparticles; 2) Preparation of water-soluble iron oxide nanoparticles; 3) Preparation of surface-functionalized iron oxide nanoparticles; Step 3) includes surface carboxylation modification of the water-soluble iron oxide nanoparticles obtained in step 2) using organic acids and alcohols at room temperature; The organic acid includes polyacrylic acid, polylactic acid, citric acid, or polyvinyl acid; the alcohol includes ethylene glycol or polyethylene glycol with a molecular weight of 1,000 to 20,000. Step 2) includes dispersing the iron oxide nanoparticles obtained in step 1) in an aqueous solution containing a surfactant; the surfactant includes hexadecyltrimethylammonium bromide, hexadecyltrimethylammonium chloride, dodecyltrimethylammonium bromide or dodecyltrimethylammonium chloride; The dispersion temperature in step 2) is 40 to 100 degrees Celsius.

2. The application according to claim 1, characterized in that, The iron oxide nanoparticles prepared in step 1) have a particle size of 15-40 nanometers and an average particle size of 25 nanometers.

3. The application according to claim 1, characterized in that, The surface-functionalized iron oxide nanoparticles obtained in step 3) have a particle size of 70–300 nm and an average particle size of 115 nm.

4. The application according to claim 1, characterized in that, The activation time is 0.5 to 10 hours, and the connection reaction time is 0.5 to 48 hours.

5. The application according to claim 1, characterized in that, The surface-functionalized iron oxide nanoparticles, which are connected to near-infrared II fluorescent molecules indocyanine green, proteins, viruses, or DNA, have a particle size of 70–500 nm and an average particle size of 143.6 nm.

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