CN111388667B - Ferroferric oxide nanoparticle surface modification method, modified material and application thereof - Google Patents
Ferroferric oxide nanoparticle surface modification method, modified material and application thereof Download PDFInfo
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Abstract
A ferroferric oxide nano particle surface modification method, a modified material and application thereof belong to the field of biomedical nano materials. The ferroferric oxide nanoparticle surface modification method comprises the steps of carrying out condensation reflux reaction on uniformly mixed ferroferric oxide nanoparticles, 3-glycidyloxypropyltrimethoxysilane and a first solvent at 50-70 ℃ for 3-6 hours to prepare epoxy-based ferroferric oxide nanoparticles; and adjusting the pH value of the uniformly mixed epoxy ferroferric oxide nanoparticles, cysteine-alanine-glycine polypeptide and a second solvent to 8-9, and performing condensation reflux reaction at 70-90 ℃ for 4-6 hours to obtain the ferroferric oxide nanoparticles with the surface modified with CAG polypeptide. The CAG polypeptide is introduced to the surface of the ferroferric oxide nano particle in a covalent bonding mode, and the ferroferric oxide nano particle with the surface modified with the CAG polypeptide can keep the magnetic property of the ferroferric oxide nano particle and the function of the CAG polypeptide.
Description
Technical Field
The application relates to the field of biomedical nano materials, in particular to a ferroferric oxide nano particle surface modification method, a modified material and application thereof.
Background
Interventional therapy is currently the predominant clinical treatment for atherosclerosis. Under the guidance and observation of imaging equipment, interventional therapy has the advantages of accuracy, safety, high efficiency, wide application range, few complications and the like. However, during the interventional operation, when the sheath of the radial artery is inserted and removed and the guiding catheter is manipulated and rotated, the damage of the structure and the function of the access blood vessel is inevitably caused, wherein the intimal damage is the most serious damage. Under the action of foreign matters, the endothelial cell layer is damaged, and smooth muscle cells are exposed in the blood environment to induce the proliferation of the smooth muscle cells, so that the vascular occlusion is easily caused. At present, small-diameter sheath tubes, short-time compression hemostasis, anticoagulant and other modes are generally adopted clinically to reduce or control complications caused by the damage to access blood vessels in interventional operations. However, these clinically used modalities are often not specific and do not allow specific treatment of normal access vascular lesions.
Disclosure of Invention
The application provides a ferroferric oxide nanoparticle surface modification method, a modified material and application thereof, wherein the ferroferric oxide nanoparticle surface modified material has the characteristic of being capable of moving towards a target position under the action of an external magnetic field, and can be used for controllably positioning and enriching a damaged part of a blood vessel in vivo so as to quickly proliferate and repair the damaged vascular endothelium.
The embodiment of the application is realized as follows:
in a first aspect, the present application provides a method for modifying a surface of a ferroferric oxide nanoparticle, including:
condensing and refluxing the uniformly mixed ferroferric oxide nanoparticles, 3-glycidyloxypropyltrimethoxysilane and a first solvent at 50-70 ℃ for 3-6 h to obtain the epoxy ferroferric oxide nanoparticles.
And then adjusting the pH value of the uniformly mixed epoxy ferroferric oxide nanoparticles, cysteine-alanine-glycine polypeptide and a second solvent to 8-9, and performing condensation reflux reaction at 70-90 ℃ for 4-6 hours to obtain the ferroferric oxide nanoparticles with the surface modified with CAG polypeptide.
In the technical scheme, the ferroferric oxide nano particles (Fe)3O4) The surface modification method comprises two steps, wherein the first step is to react 3-glycidyloxypropyltrimethoxysilane (KH560) with ferroferric oxide particles to modify KH560 on the surfaces of the ferroferric oxide particles to form epoxy ferroferric oxide nanoparticles (Fe)3O4-EP); the second step is to react the epoxy ferroferric oxide nano particles with cysteine-alanine-glycine (Cys-Ala-Gly, CAG) polypeptide to ensure that the ferroferric oxide nano particles are directionally combined with amino at the nitrogen end of cysteine on the CAG through the open loop of the epoxy group on the surface of the ferroferric oxide nano particles to form the ferroferric oxide nano particles (Fe) the surface of which is modified with the CAG polypeptide3O4-CAG). The preparation method is simple.
According to the preparation method, the CAG polypeptide is introduced to the surface of the ferroferric oxide nano particle in a covalent bonding mode, the ferroferric oxide nano particle with stable performance and the surface modified with the CAG polypeptide can be prepared, and the ferroferric oxide nano particle with the surface modified with the CAG polypeptide can keep the magnetic performance of the ferroferric oxide nano particle and the function of the CAG polypeptide.
With reference to the first aspect, in a first possible example of the first aspect of the present application, a mass-to-volume ratio of the ferroferric oxide nanoparticles to the first solvent is 1 to 3: 30g/mL, and the mass-volume ratio of the ferroferric oxide nanoparticles to the 3-glycidyloxypropyltrimethoxysilane is 1: 1.5-15 g/mL.
In a second possible example of the first aspect of the present application, in combination with the first aspect, the first solvent includes a 90% to 95% ethanol solution by mass fraction.
In the above example, KH560 is hydrolyzed in water, and therefore the first solvent needs to be an organic solvent having a good dispersibility for ferroferric oxide and a low water content.
With reference to the first aspect, in a third possible example of the first aspect of the present application, the uniformly mixed iron oxide nanoparticles, 3-glycidyloxypropyltrimethoxysilane, and the first solvent are condensed and refluxed at 50 to 70 ℃ for 3 to 6 hours to obtain a first mixture, and a magnet and absolute ethanol are used to remove impurities in the first mixture to obtain the epoxidized iron oxide nanoparticles.
In the above example, since magnetite is magnetic, the epoxy-modified magnetite nanoparticles were adsorbed to the bottom of the container by using a magnet, and the epoxy-modified magnetite nanoparticles were washed with absolute ethanol several times to remove unreacted KH 560.
In a fourth possible example of the first aspect of the present application, in combination with the first aspect, the epoxy group and cysteine-alanine-glycine polypeptide of the epoxidized ferroferric oxide nanoparticles have a molar ratio of 1:1 to 2, and the ratio of the mass to volume of the epoxidized ferroferric oxide nanoparticles to the second solvent is 0.8 to 2: 30 g/mL.
In a fifth possible example of the first aspect of the present application in combination with the first aspect, the second solvent includes absolute ethanol.
In the above examples, the second solvent needs to be highly dispersible with respect to the epoxidized magnetite.
With reference to the first aspect, in a sixth possible example of the first aspect of the present application, the mixed epoxidized ferroferric oxide nanoparticles with the pH of 8 to 9, cysteine-alanine-glycine polypeptide, and a second solvent are subjected to a condensation reflux reaction at 70 to 90 ℃ for 4 to 6 hours to obtain a second mixture, and a magnet and absolute ethyl alcohol are used to remove impurities in the second mixture to obtain the ferroferric oxide nanoparticles with the surface modified with CAG polypeptides.
In the above example, since the ferroferric oxide is magnetic, the ferroferric oxide nanoparticles with the surface modified with the CAG polypeptide are adsorbed at the bottom of the container by using a magnet, and the ferroferric oxide nanoparticles with the surface modified with the CAG polypeptide are washed by using absolute ethyl alcohol for multiple times to remove the CAG polypeptide which does not participate in the reaction.
In a seventh possible example of the first aspect of the present application in combination with the first aspect, the pH is adjusted to 8 to 9 with an alkaline solution having a concentration of 0.5 to 5 mol/L.
In a second aspect, the present application provides a ferroferric oxide nanoparticle surface modification material, which is obtained by modifying according to the above-mentioned ferroferric oxide nanoparticle surface modification method.
In the technical scheme, the ferroferric oxide nanoparticle surface modification material has the characteristic of being capable of moving towards a target position under the action of an external magnetic field, and can be used for controllably positioning and enriching a damaged part of a blood vessel in vivo so as to quickly proliferate and repair the damaged vascular endothelium.
In a third aspect, the application example provides an application of the ferroferric oxide nanoparticle surface modification material in positioning control of endothelial cell activity.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings that are required to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present application and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained from the drawings without inventive effort.
FIG. 1 is a schematic diagram of a ferroferric oxide nanoparticle surface modification method according to the application;
FIG. 2 is a graph showing hydrated particle sizes of different particle samples in test example 1 of the present application;
FIG. 3 is a simulation diagram of the content of polypeptides on the surface of ferroferric oxide nanoparticles measured by a DTNB method in test example 2 of the present application;
FIG. 4 shows the influence of an external magnetic field on ferroferric oxide nanoparticles before and after modification in test example 3 of the present application;
FIG. 5 is a fluorescence chart of cells obtained after culturing different samples and endothelial cells for 1 day and 3 days in test example 4 of the present application.
Detailed Description
Embodiments of the present application will be described in detail below with reference to examples, but those skilled in the art will appreciate that the following examples are only illustrative of the present application and should not be construed as limiting the scope of the present application. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
The magnetic ferroferric oxide nano-particles have good biocompatibility and are widely applied to the aspects of biomedicine, biomedical imaging, nuclear magnetic resonance, biological target materials, microwave absorption, magnetic separation, thermal therapy and the like at present. The magnetic ferroferric oxide nano-particles have a large number of hydroxyl groups on the surface, so that different functional characteristics can be endowed to the particles by a surface modification means.
The CAG polypeptide is a specific tripeptide structure found in type IV collagen in 2012, can improve the activity of endothelial cells, can inhibit smooth muscle cells and has the function of selectively promoting cell proliferation.
The inventor thinks that the magnetic ferroferric oxide nano-particles can move towards a target position under the action of an external magnetic field, and if CAG polypeptides are modified on the surfaces of the magnetic ferroferric oxide nano-particles, the CAG polypeptides can be brought to the target position to rapidly proliferate and repair damaged vascular endothelium.
However, the CAG polypeptide cannot be directly modified on the surface of the magnetic ferroferric oxide nanoparticles.
The following specific description is made for a ferroferric oxide nanoparticle surface modification method, a modified material and an application thereof in the embodiments of the present application:
the application provides a method for modifying the surface of ferroferric oxide nanoparticles, please refer to fig. 1, which comprises the following steps:
(1) preparation of epoxidized ferroferric oxide nanoparticles
Adding ferroferric oxide nanoparticles into a first solvent, performing ultrasonic dispersion to obtain a first dispersion solution, adding KH560 into the first dispersion solution, uniformly stirring in a water bath/oil bath environment at 50-70 ℃, and performing condensation reflux reaction for 3-6 hours to obtain a second dispersion solution;
and pouring the second dispersion liquid into a container, placing a magnet at the bottom of the container, adsorbing the epoxy ferroferric oxide nanoparticles by the magnet through the wall of the container, pouring out the solvent, adding absolute ethyl alcohol, uniformly dispersing by using an oscillator, continuing placing the magnet at the bottom of the container, adsorbing the epoxy ferroferric oxide nanoparticles by the magnet through the wall of the container, pouring out the solvent, repeatedly washing and adsorbing for 3-5 times to remove KH560 which does not participate in the reaction, and thus obtaining the epoxy ferroferric oxide nanoparticles.
The mass volume ratio of the ferroferric oxide nanoparticles to the first solvent is 1-3: 30g/mL, and the mass-volume ratio of the ferroferric oxide nanoparticles to the 3-glycidyloxypropyltrimethoxysilane is 1: 1.5-15 g/mL.
Optionally, the first solvent comprises 90-95% by mass of ethanol solution or toluene.
Since KH560 has an epoxy group that rapidly opens in water, the first solvent must have a low water content and a good dispersibility for the ferroferric oxide nanoparticles in order to prevent rapid opening. The ferroferric oxide nano particles have good dispersibility in absolute ethyl alcohol, but the silane coupling agent is not easy to react with the ferroferric oxide nano particles in an anhydrous environment. The ferroferric oxide nano particles have good dispersibility in 90-95% ethanol solution and toluene, and KH560 basically cannot open rings in 90-95% ethanol solution.
Optionally, the dispersing time is 5-10 min.
The dispersion time is too short, the dispersion is not uniform, and the dispersion time is too long, so that the ferroferric oxide nano particles are oxidized or the performance is changed due to overheating.
The prepared epoxy ferroferric oxide nanoparticles can be added into absolute ethyl alcohol to enable the epoxy ferroferric oxide nanoparticles to be completely immersed in the absolute ethyl alcohol, and the epoxy ferroferric oxide nanoparticles are refrigerated and stored in an environment of 0-4 ℃. The absolute ethyl alcohol can prevent the epoxy ferroferric oxide nano particles from contacting with the outside air, and the surface groups of the epoxy ferroferric oxide nano particles are prevented from being oxidized.
(2) Preparation of ferroferric oxide nanoparticles with modified CAG polypeptides on surfaces
Adding epoxy ferroferric oxide nanoparticles into a second solvent, performing ultrasonic dispersion to obtain a third dispersion liquid, adding CAG polypeptide into the third dispersion liquid, adjusting the pH value of the third dispersion liquid to 8-9, uniformly stirring in a water bath/oil bath environment at 70-90 ℃, and performing condensation reflux reaction for 3-6 hours to obtain a fourth dispersion liquid;
pouring the fourth dispersion liquid into a container, placing a magnet at the bottom of the container, adsorbing the ferroferric oxide nanoparticles modified with the CAG polypeptide by the magnet through the wall of the container, pouring out the solvent, adding absolute ethyl alcohol, dispersing uniformly by using an oscillator, continuing to place the magnet at the bottom of the container, adsorbing the ferroferric oxide nanoparticles modified with the CAG polypeptide by the magnet through the wall of the container, pouring out the solvent, repeatedly washing and adsorbing for 3-5 times to remove KH560 not participating in the reaction, and thus obtaining the ferroferric oxide nanoparticles modified with the CAG polypeptide.
Wherein the molar ratio of epoxy groups of the epoxidized ferroferric oxide nanoparticles to CAG polypeptide is 1: 1-2, and the mass-volume ratio of the epoxidized ferroferric oxide nanoparticles to the second solvent is 0.8-2: 30 g/mL.
Optionally, the mass-to-volume ratio of the epoxidized ferroferric oxide nanoparticles to the second solvent is 0.8-1.2: 30 g/mL.
Optionally, the second solvent comprises absolute ethanol.
Optionally, the dispersing time is 3-6 min.
The dispersion time is too short, the dispersion is not uniform, and the dispersion time is too long, so that the epoxy ferroferric oxide nano particles are oxidized or the performance of the epoxy ferroferric oxide nano particles is changed due to overheating.
The prepared ferroferric oxide nano particles modified with the CAG polypeptide can be added into absolute ethyl alcohol to enable the ferroferric oxide nano particles modified with the CAG polypeptide to be completely immersed in the absolute ethyl alcohol, and the ferroferric oxide nano particles are refrigerated and stored in an environment of-15 to 25 ℃. The absolute ethyl alcohol can prevent the ferroferric oxide nano particles modified with the CAG polypeptide from contacting with the outside air, and the surface groups of the ferroferric oxide nano particles modified with the CAG polypeptide are prevented from being oxidized.
And adjusting the pH value of the third dispersion liquid to 8-9 by adopting an alkaline solution with the concentration of 0.5-5 mol/L.
Wherein the alkaline solution comprises a sodium hydroxide solution or a potassium hydroxide solution.
The inventor finds that although hydroxyl on the surface of the ferroferric oxide nano particle cannot directly react with the CAG polypeptide, KH560 reacts with the ferroferric oxide nano particle to introduce epoxy groups into the ferroferric oxide nano particle, and the open loop of the epoxy groups can be covalently combined with amino groups on the CAG polypeptide, so that the CAG polypeptide is introduced onto the surface of the ferroferric oxide nano particle. The covalent introduction mode does not change the magnetism of the ferroferric oxide nano particles and does not influence the function of the polypeptide.
The application also provides a ferroferric oxide nanoparticle surface modification material which is obtained by modification according to the ferroferric oxide nanoparticle surface modification method.
The ferroferric oxide nanoparticle surface modification material has the characteristic of being capable of moving towards a target position under the action of an external magnetic field, and can be used for controllably positioning and enriching a damaged part of a blood vessel in vivo so as to quickly proliferate and repair the damaged vascular endothelium.
The application also provides an application of the ferroferric oxide nanoparticle surface modification material in positioning and controlling the activity of endothelial cells.
The ferroferric oxide nanoparticle surface modification material is prepared into a solution to be injected into a human body, under the action of a magnetic field, the ferroferric oxide nanoparticle surface modification material is controllably positioned and enriched to the damaged part of a blood vessel, and the CAG polypeptide can be directly contacted with endothelial cells, so that the critical effects of selectively promoting the rapid growth and proliferation of the endothelial cells and maintaining the activity of the cells are rapidly exerted.
The method for modifying the surface of the ferroferric oxide nano particles, the modified material and the application thereof are further described in detail by combining with the examples.
Example 1
The embodiment of the application provides a ferroferric oxide nanoparticle surface modification method and a modified material, and the method comprises the following steps:
1. preparation of epoxidized ferroferric oxide nanoparticles
Adding 1.5g of ferroferric oxide nanoparticles into 30mL of 90% ethanol solution by mass, performing ultrasonic dispersion for 10min to obtain a first dispersion solution, adding 2.25mL of KH560 into the first dispersion solution, uniformly stirring in a water bath environment at 60 ℃, and performing condensation reflux reaction for 6h to obtain a second dispersion solution;
and pouring the second dispersion liquid into a container, placing a magnet at the bottom of the container, adsorbing the epoxy ferroferric oxide nanoparticles by the magnet through the wall of the container, pouring out the solvent, adding absolute ethyl alcohol, uniformly dispersing by using an oscillator, continuing placing the magnet at the bottom of the container, adsorbing the epoxy ferroferric oxide nanoparticles by the magnet through the wall of the container, pouring out the solvent, repeatedly washing and adsorbing for 3 times to remove KH560 which does not participate in the reaction, and thus obtaining the epoxy ferroferric oxide nanoparticles.
2. Preparation of ferroferric oxide nanoparticles with modified CAG polypeptides on surfaces
Adding 1g of epoxy ferroferric oxide nanoparticles into 30mL of absolute ethyl alcohol, performing ultrasonic dispersion for 5min to obtain a third dispersion liquid, adding CAG polypeptide into the third dispersion liquid, wherein the molar ratio of epoxy groups of the epoxy ferroferric oxide nanoparticles to the added CAG polypeptide is 1:1, adjusting the pH value of the third dispersion liquid to 8, uniformly stirring in a 70 ℃ water bath/oil bath environment, and performing condensation reflux reaction for 6h to obtain a fourth dispersion liquid;
pouring the fourth dispersion liquid into a container, placing a magnet at the bottom of the container, adsorbing and modifying the ferroferric oxide nanoparticles with the CAG polypeptide by the magnet through the wall of the container, pouring out the solvent, adding absolute ethyl alcohol, uniformly dispersing by using an oscillator, continuing to place the magnet at the bottom of the container, adsorbing and modifying the ferroferric oxide nanoparticles with the CAG polypeptide by the magnet through the wall of the container, pouring out the solvent, repeatedly operating for 3 times, washing, adsorbing and removing KH560 which does not participate in the reaction to obtain the ferroferric oxide nanoparticle surface modification material.
Example 2
The embodiment of the application provides a ferroferric oxide nanoparticle surface modification method and a modified material, and the method comprises the following steps:
1. preparation of epoxidized ferroferric oxide nanoparticles
Adding 2g of ferroferric oxide nanoparticles into 30mL of 90% ethanol solution, performing ultrasonic dispersion for 10min to obtain a first dispersion solution, adding 5mL of KH560 into the first dispersion solution, uniformly stirring in a water bath environment at 70 ℃, and performing condensation reflux reaction for 5h to obtain a second dispersion solution;
and pouring the second dispersion liquid into a container, placing a magnet at the bottom of the container, adsorbing the epoxy ferroferric oxide nanoparticles by the magnet through the wall of the container, pouring out the solvent, adding absolute ethyl alcohol, uniformly dispersing by using an oscillator, continuing placing the magnet at the bottom of the container, adsorbing the epoxy ferroferric oxide nanoparticles by the magnet through the wall of the container, pouring out the solvent, and repeatedly washing and adsorbing for 4 times to remove KH560 which does not participate in the reaction to obtain the epoxy ferroferric oxide nanoparticles.
2. Preparation of ferroferric oxide nanoparticles with modified CAG polypeptides on surfaces
Adding 1.2g of epoxy ferroferric oxide nanoparticles into 30mL of absolute ethyl alcohol, performing ultrasonic dispersion for 5min to obtain a third dispersion liquid, adding CAG polypeptide into the third dispersion liquid, wherein the molar ratio of epoxy groups of the epoxy ferroferric oxide nanoparticles to the added CAG polypeptide is 1:1, adjusting the pH value of the third dispersion liquid to 8, uniformly stirring in a 70 ℃ water bath/oil bath environment, and performing condensation reflux reaction for 6h to obtain a fourth dispersion liquid;
pouring the fourth dispersion liquid into a container, placing a magnet at the bottom of the container, adsorbing and modifying the ferroferric oxide nanoparticles with the CAG polypeptide by the magnet through the wall of the container, pouring out the solvent, adding absolute ethyl alcohol, uniformly dispersing by using an oscillator, continuing to place the magnet at the bottom of the container, adsorbing and modifying the ferroferric oxide nanoparticles with the CAG polypeptide by the magnet through the wall of the container, pouring out the solvent, repeatedly washing and adsorbing for 4 times to remove KH560 which does not participate in the reaction, and thus obtaining the ferroferric oxide nanoparticle surface modification material.
Example 3
The embodiment of the application provides a ferroferric oxide nanoparticle surface modification method and a modified material, and the method comprises the following steps:
1. preparation of epoxidized ferroferric oxide nanoparticles
Adding 3g of ferroferric oxide nanoparticles into 30mL of 90% ethanol solution by mass, performing ultrasonic dispersion for 10min to obtain a first dispersion solution, adding 7.5mL of KH560 into the first dispersion solution, uniformly stirring in a water bath environment at 70 ℃, and performing condensation reflux reaction for 5h to obtain a second dispersion solution;
and pouring the second dispersion liquid into a container, placing a magnet at the bottom of the container, adsorbing the epoxy ferroferric oxide nanoparticles by the magnet through the wall of the container, pouring out the solvent, adding absolute ethyl alcohol, uniformly dispersing by using an oscillator, continuing placing the magnet at the bottom of the container, adsorbing the epoxy ferroferric oxide nanoparticles by the magnet through the wall of the container, pouring out the solvent, repeatedly washing and adsorbing for 3 times to remove KH560 which does not participate in the reaction, and thus obtaining the epoxy ferroferric oxide nanoparticles.
2. Preparation of ferroferric oxide nanoparticles with modified CAG polypeptides on surfaces
Adding 1g of epoxy ferroferric oxide nanoparticles into 30mL of absolute ethyl alcohol, performing ultrasonic dispersion for 5min to obtain a third dispersion liquid, adding CAG polypeptide into the third dispersion liquid, wherein the molar ratio of epoxy groups of the epoxy ferroferric oxide nanoparticles to the added CAG polypeptide is 1:2, adjusting the pH value of the third dispersion liquid to 9, uniformly stirring in a water bath environment at 80 ℃, and performing condensation reflux reaction for 5h to obtain a fourth dispersion liquid;
pouring the fourth dispersion liquid into a container, placing a magnet at the bottom of the container, adsorbing and modifying the ferroferric oxide nanoparticles with the CAG polypeptide by the magnet through the wall of the container, pouring out the solvent, adding absolute ethyl alcohol, uniformly dispersing by using an oscillator, continuing to place the magnet at the bottom of the container, adsorbing and modifying the ferroferric oxide nanoparticles with the CAG polypeptide by the magnet through the wall of the container, pouring out the solvent, repeatedly operating for 3 times, washing, adsorbing and removing KH560 which does not participate in the reaction to obtain the ferroferric oxide nanoparticle surface modification material.
Example 4
The embodiment of the application provides a ferroferric oxide nanoparticle surface modification method and a modified material, and the method comprises the following steps:
1. preparation of epoxidized ferroferric oxide nanoparticles
Adding 1g of ferroferric oxide nanoparticles into 30mL of 90% ethanol solution by mass, performing ultrasonic dispersion for 10min to obtain a first dispersion solution, adding 10mL of KH560 into the first dispersion solution, uniformly stirring in a water bath environment at 80 ℃, and performing condensation reflux reaction for 4h to obtain a second dispersion solution;
and pouring the second dispersion liquid into a container, placing a magnet at the bottom of the container, adsorbing the epoxy ferroferric oxide nanoparticles by the magnet through the wall of the container, pouring out the solvent, adding absolute ethyl alcohol, uniformly dispersing by using an oscillator, continuing placing the magnet at the bottom of the container, adsorbing the epoxy ferroferric oxide nanoparticles by the magnet through the wall of the container, pouring out the solvent, repeatedly washing and adsorbing for 5 times to remove KH560 which does not participate in the reaction, and thus obtaining the epoxy ferroferric oxide nanoparticles.
2. Preparation of ferroferric oxide nanoparticles with modified CAG polypeptides on surfaces
Adding 0.8g of epoxy ferroferric oxide nanoparticles into 30mL of absolute ethyl alcohol, performing ultrasonic dispersion for 5min to obtain a third dispersion liquid, adding CAG polypeptide into the third dispersion liquid, wherein the molar ratio of epoxy groups of the epoxy ferroferric oxide nanoparticles to the added CAG polypeptide is 1:1, adjusting the pH value of the third dispersion liquid to 8, uniformly stirring in a water bath environment at 80 ℃, and performing condensation reflux reaction for 6h to obtain the fourth dispersion liquid;
pouring the fourth dispersion liquid into a container, placing a magnet at the bottom of the container, adsorbing and modifying the ferroferric oxide nanoparticles with the CAG polypeptide by the magnet through the wall of the container, pouring out the solvent, adding absolute ethyl alcohol, uniformly dispersing by using an oscillator, continuing to place the magnet at the bottom of the container, adsorbing and modifying the ferroferric oxide nanoparticles with the CAG polypeptide by the magnet through the wall of the container, pouring out the solvent, repeatedly washing and adsorbing for 5 times to remove KH560 which does not participate in the reaction, and thus obtaining the ferroferric oxide nanoparticle surface modification material.
Example 5
The embodiment of the application provides a ferroferric oxide nanoparticle surface modification method and a modified material, and the method comprises the following steps:
1. preparation of epoxidized ferroferric oxide nanoparticles
Adding 1.2g of ferroferric oxide nanoparticles into 30mL of 90% ethanol solution by mass, performing ultrasonic dispersion for 10min to obtain a first dispersion solution, adding 18mL of KH560 into the first dispersion solution, uniformly stirring in a water bath environment at 80 ℃, and performing condensation reflux reaction for 3h to obtain a second dispersion solution;
and pouring the second dispersion liquid into a container, placing a magnet at the bottom of the container, adsorbing the epoxy ferroferric oxide nanoparticles by the magnet through the wall of the container, pouring out the solvent, adding absolute ethyl alcohol, uniformly dispersing by using an oscillator, continuing placing the magnet at the bottom of the container, adsorbing the epoxy ferroferric oxide nanoparticles by the magnet through the wall of the container, pouring out the solvent, and repeatedly washing and adsorbing for 4 times to remove KH560 which does not participate in the reaction to obtain the epoxy ferroferric oxide nanoparticles.
2. Preparation of ferroferric oxide nanoparticles with modified CAG polypeptides on surfaces
Adding 1g of epoxy ferroferric oxide nanoparticles into 30mL of absolute ethyl alcohol, performing ultrasonic dispersion for 5min to obtain a third dispersion liquid, adding CAG polypeptide into the third dispersion liquid, wherein the molar ratio of epoxy groups of the epoxy ferroferric oxide nanoparticles to the added CAG polypeptide is 1:1, adjusting the pH value of the third dispersion liquid to 8, uniformly stirring in a 70 ℃ water bath environment, and performing condensation reflux reaction for 6h to obtain a fourth dispersion liquid;
pouring the fourth dispersion liquid into a container, placing a magnet at the bottom of the container, adsorbing and modifying the ferroferric oxide nanoparticles with the CAG polypeptide by the magnet through the wall of the container, pouring out the solvent, adding absolute ethyl alcohol, uniformly dispersing by using an oscillator, continuing to place the magnet at the bottom of the container, adsorbing and modifying the ferroferric oxide nanoparticles with the CAG polypeptide by the magnet through the wall of the container, pouring out the solvent, repeatedly washing and adsorbing for 4 times to remove KH560 which does not participate in the reaction, and thus obtaining the ferroferric oxide nanoparticle surface modification material.
Example 6
The embodiment of the application provides a ferroferric oxide nanoparticle surface modification method and a modified material, and the method comprises the following steps:
1. preparation of epoxidized ferroferric oxide nanoparticles
Adding 2g of ferroferric oxide nanoparticles into 30mL of 90% ethanol solution, performing ultrasonic dispersion for 10min to obtain a first dispersion solution, adding 30mL of KH560 into the first dispersion solution, uniformly stirring in a water bath environment at 80 ℃, and performing condensation reflux reaction for 3h to obtain a second dispersion solution;
and pouring the second dispersion liquid into a container, placing a magnet at the bottom of the container, adsorbing the epoxy ferroferric oxide nanoparticles by the magnet through the wall of the container, pouring out the solvent, adding absolute ethyl alcohol, uniformly dispersing by using an oscillator, continuing placing the magnet at the bottom of the container, adsorbing the epoxy ferroferric oxide nanoparticles by the magnet through the wall of the container, pouring out the solvent, and repeatedly washing and adsorbing for 4 times to remove KH560 which does not participate in the reaction to obtain the epoxy ferroferric oxide nanoparticles.
2. Preparation of ferroferric oxide nanoparticles with modified CAG polypeptides on surfaces
Adding 1g of epoxy ferroferric oxide nanoparticles into 30mL of absolute ethyl alcohol, performing ultrasonic dispersion for 5min to obtain a third dispersion liquid, adding CAG polypeptide into the third dispersion liquid, wherein the molar ratio of epoxy groups of the epoxy ferroferric oxide nanoparticles to the added CAG polypeptide is 1:2, adjusting the pH value of the third dispersion liquid to 9, uniformly stirring in a water bath environment at 80 ℃, and performing condensation reflux reaction for 5h to obtain a fourth dispersion liquid;
pouring the fourth dispersion liquid into a container, placing a magnet at the bottom of the container, adsorbing and modifying the ferroferric oxide nanoparticles with the CAG polypeptide by the magnet through the wall of the container, pouring out the solvent, adding absolute ethyl alcohol, uniformly dispersing by using an oscillator, continuing to place the magnet at the bottom of the container, adsorbing and modifying the ferroferric oxide nanoparticles with the CAG polypeptide by the magnet through the wall of the container, pouring out the solvent, repeatedly washing and adsorbing for 4 times to remove KH560 which does not participate in the reaction, and thus obtaining the ferroferric oxide nanoparticle surface modification material.
Test example 1
And (3) respectively dispersing ferroferric oxide nanoparticles, epoxy ferroferric oxide nanoparticles and ferroferric oxide nanoparticles with modified CAG polypeptides in RO water, and detecting the hydration particle diameters of three groups of samples in a DLS laser particle size analyzer.
As shown in fig. 2, the ferriferrous oxide nanoparticles are easy to agglomerate in the aqueous solution, so the hydrated particle size is relatively large, and after the KH560 and the CAG polypeptide are respectively introduced into the epoxy ferriferrous oxide nanoparticles and the ferriferrous oxide nanoparticles with the surface modified with the CAG polypeptide, the inter-particle distance is increased, the inter-particle influence is reduced, the dispersibility is improved, and the hydrated particle size is reduced.
Test example 2
DTNB is a compound that can react with a thiol-containing material. When DTNB reacts with one mole of thiol, one mole of negative divalent anion is produced, which appears yellow with a significant change in absorbance at 412 nm. The content of the polypeptide on the surface of the ferroferric oxide nano particle can be qualitatively and quantitatively detected.
Preparing CAG polypeptide standard solution with the concentration of 1mmol/L, DTNB standard solution with the concentration of 0.01mol/L and DTNB analysis solution with the concentration of 0.0001 mol/L. 2ml of the TNB assay solution was added to each of 6 tubes and placed in a water bath at 25 ℃. And adding CAG polypeptide standard solution into another 5 centrifuge tubes according to the volume of 100uL, 140uL, 220uL, 300uL and 380uL, diluting the CAG polypeptide standard solution by using buffer solution for 2mL, and calculating the concentration of the CAG polypeptide in each centrifuge tube. Then taking 400uL of the solution diluted in each centrifuge tube, adding the solution into DTNB analysis solution, adding 400uL of buffer solution into a blank control group, reacting for 10min, detecting the absorbance value at 412nm by using an enzyme-labeling instrument, and calculating the standard curve of CAG polypeptide as shown in figure 3.
Weighing a mass of Fe3O4CAG was dispersed in buffer, diluted to 2mL, 400uL was added to the treated DTNB assay solution, reacted for 10min, its absorbance at 412nm was measured, and Fe was calculated3O4Content of CAG polypeptide in CAG. The content of the polypeptide on the surfaces of the ferroferric oxide nanoparticles measured by a DTNB method is 6.1 x 10-3-8.7*10- 3mmol/g。
Test example 3
As shown in fig. 4, magnets are respectively placed on one side of a container containing ferroferric oxide nanoparticles and ferroferric oxide nanoparticle surface modification materials, and it is found that the ferroferric oxide nanoparticles and the ferroferric oxide nanoparticle surface modification materials can be enriched, that is, the ferroferric oxide nanoparticle surface modification materials prepared by introducing CAG polypeptides onto the surfaces of the ferroferric oxide nanoparticles in a covalent manner also have magnetism.
Test example 4
And (3) taking the same mass of ferroferric oxide nanoparticles and ferroferric oxide nanoparticle surface modification materials, performing ultraviolet sterilization, and then respectively adding a certain amount of cell culture medium to dilute to the same volume. Endothelial cells were added to the 24-well plates in an amount of 1 ten thousand units per well. Then adding different particle solutions with the same volume respectively, adding cell culture medium with the same volume into the blank control sample, and adding the cell culture medium in 5% CO2And cultured at 37 ℃ for 1 day and 3 days, then fixed, stained with rhodamine, and the cells were observed under an inverted fluorescence microscope.
As shown in fig. 5, after endothelial cells, endothelial cells and ferroferric oxide nanoparticles are mixed and cultured for 1 day and 3 days, respectively, the fluorescence images of the cells are measured, wherein a is the fluorescence image of the cells cultured for 1 day and 3 days by the endothelial cells, B is the fluorescence image of the cells cultured for 1 day and 3 days by the endothelial cells and the ferroferric oxide nanoparticles, and C is the fluorescence image of the cells cultured for 1 day and 3 days by the endothelial cells and the ferroferric oxide nanoparticle surface modification materials.
Comparing the time A and the time B at 1 day in the figure 5, the endothelial cells obtained after the endothelial cells and the ferroferric oxide nano particles are mixed and cultured for 1 day are fewer than those obtained after the endothelial cells are separately cultured for one day, namely, the ferroferric oxide nano particles are proved to have no function of promoting cell proliferation on the endothelial cells;
compared with A and C at 1 day and 3 days in the figure 5, the endothelial cells obtained after the endothelial cells and the ferroferric oxide nanoparticle surface modification material are mixed and cultured for 1 day and 3 days are more than those obtained after the endothelial cells are independently cultured for one day, so that the ferroferric oxide nanoparticle surface modification material is proved to have the function of promoting cell proliferation.
The foregoing is illustrative of the present application and is not to be construed as limiting thereof, as numerous modifications and variations will be apparent to those skilled in the art. Any modification, equivalent replacement, improvement and the like made within the spirit and principle of the present application shall be included in the protection scope of the present application.
Claims (8)
1. A ferroferric oxide nanoparticle surface modification method is characterized by comprising the following steps:
condensing and refluxing the uniformly mixed ferroferric oxide nanoparticles, 3-glycidyloxypropyltrimethoxysilane and a first solvent at 70 ℃ for 3-6 h to obtain epoxy ferroferric oxide nanoparticles;
adjusting the pH value of the uniformly mixed epoxy ferroferric oxide nanoparticles, cysteine-alanine-glycine polypeptide and a second solvent to 8-9, and performing condensation reflux reaction at 70-90 ℃ for 4-6 hours to obtain ferroferric oxide nanoparticles with the surface modified with CAG polypeptide;
the mass volume ratio of the ferroferric oxide nanoparticles to the first solvent is 1-3: 30g/mL, wherein the mass-volume ratio of the ferroferric oxide nanoparticles to the 3-glycidyloxypropyltrimethoxysilane is 1: 1.5-15 g/mL;
the first solvent is an ethanol solution with the mass fraction of 90-95%.
2. The ferroferric oxide nanoparticle surface modification method according to claim 1, wherein the uniformly mixed ferroferric oxide nanoparticles, the 3-glycidyloxypropyltrimethoxysilane and the first solvent are subjected to condensation reflux reaction at 70 ℃ for 3-6 hours to obtain a first mixture, and the impurities in the first mixture are removed by using a magnet and absolute ethyl alcohol to obtain the epoxidized ferroferric oxide nanoparticles.
3. The ferroferric oxide nanoparticle surface modification method according to claim 1, wherein the molar ratio of epoxy groups of the epoxidized ferroferric oxide nanoparticles to the cysteine-alanine-glycine polypeptide is 1: 1-2, and the mass-to-volume ratio of the epoxidized ferroferric oxide nanoparticles to the second solvent is 0.8-2: 30 g/mL.
4. The method for modifying the surfaces of ferroferric oxide nanoparticles according to claim 1, wherein the second solvent comprises absolute ethyl alcohol.
5. The ferroferric oxide nanoparticle surface modification method according to claim 1, wherein the mixed epoxidized ferroferric oxide nanoparticles with the pH of 8-9, cysteine-alanine-glycine polypeptide and a second solvent are subjected to condensation reflux reaction at 70-90 ℃ for 4-6 hours to obtain a second mixture, and impurities in the second mixture are removed by using a magnet and absolute ethyl alcohol to obtain the ferroferric oxide nanoparticles with the modified CAG polypeptides on the surface.
6. The ferroferric oxide nanoparticle surface modification method according to claim 1, wherein the pH is adjusted to 8-9 by using an alkaline solution with a concentration of 0.5-5 mol/L.
7. A ferroferric oxide nanoparticle surface modification material, which is characterized in that the ferroferric oxide nanoparticle surface modification material is obtained by modification according to the ferroferric oxide nanoparticle surface modification method of any one of claims 1 to 6.
8. An application of the ferroferric oxide nanoparticle surface modification material in claim 7 in preparation of a medicine for positioning and controlling endothelial cell activity.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002016519A2 (en) * | 2000-08-25 | 2002-02-28 | J.C. Hempel's Skibsfarve-Fabrik A/S | Method for thermally insulating oil and gas pipes and paint compositions for coating the inner surface of oil and gas pipes |
| CN102085380A (en) * | 2010-12-30 | 2011-06-08 | 西南交通大学 | Preparation method of nano magnetic particles for detection and treatment of coronary heart diseases |
| CN104910410A (en) * | 2015-06-05 | 2015-09-16 | 武汉理工大学 | Preparation method of RGD polypeptide grafted poly(maleic anhydride-hexamethylendiamine-DL-lactic acid)/modified hydroxyapatite porous composite material |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002016519A2 (en) * | 2000-08-25 | 2002-02-28 | J.C. Hempel's Skibsfarve-Fabrik A/S | Method for thermally insulating oil and gas pipes and paint compositions for coating the inner surface of oil and gas pipes |
| CN102085380A (en) * | 2010-12-30 | 2011-06-08 | 西南交通大学 | Preparation method of nano magnetic particles for detection and treatment of coronary heart diseases |
| CN104910410A (en) * | 2015-06-05 | 2015-09-16 | 武汉理工大学 | Preparation method of RGD polypeptide grafted poly(maleic anhydride-hexamethylendiamine-DL-lactic acid)/modified hydroxyapatite porous composite material |
Non-Patent Citations (4)
| Title |
|---|
| Collagen Type IV-Specific Tripeptides for Selective Adhesion of Endothelial and Smooth Muscle Cells;Kei Kanie, et al.;《Biotechnology and Bioengineering》;20120222;第109卷(第7期);第1808-1816页 * |
| Kei Kanie, et al..Collagen Type IV-Specific Tripeptides for Selective Adhesion of Endothelial and Smooth Muscle Cells.《Biotechnology and Bioengineering》.2012,第109卷(第7期),第1808-1816页. * |
| 张利杰等.环氧基硅烷改性磁性纳米粒子的制备与表征.《苏州科技学院学报（自然科学版）》.2013,第30卷(第1期),第45-49页. * |
| 环氧基硅烷改性磁性纳米粒子的制备与表征;张利杰等;《苏州科技学院学报（自然科学版）》;20130331;第30卷(第1期);第45-49页 * |
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