CN112168983A - Diagnosis and treatment integrated hollow carbon nano composite material and preparation method and application thereof - Google Patents
Diagnosis and treatment integrated hollow carbon nano composite material and preparation method and application thereof Download PDFInfo
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- 238000003745 diagnosis Methods 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 238000003384 imaging method Methods 0.000 claims abstract description 28
- JAOZQVJVXQKQAD-UHFFFAOYSA-K gadolinium(3+);phosphate Chemical compound [Gd+3].[O-]P([O-])([O-])=O JAOZQVJVXQKQAD-UHFFFAOYSA-K 0.000 claims abstract description 15
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- VCJMYUPGQJHHFU-UHFFFAOYSA-N iron(3+);trinitrate Chemical compound [Fe+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O VCJMYUPGQJHHFU-UHFFFAOYSA-N 0.000 claims description 4
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- A—HUMAN NECESSITIES
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- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
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- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
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Abstract
The invention relates to the technical field of functional nano materials, in particular to a diagnosis and treatment integrated hollow carbon nano composite material and a preparation method thereof. The hollow carbon nano composite material meets the requirements of photoacoustic imaging due to the hollow structure. At the same time, paramagnetic gadolinium phosphate nano particles and super-cis particles are uniformly distributed in the shell layer of the hollow carbonMagnetic gamma iron oxide nanoparticles satisfying T1Weighted imaging sum T2Weighting the imaging requirements. On the other hand, the hollow carbon material can be used as a carrier of a drug due to its own porosity, and can realize a drug delivery function. Therefore, the nano material provided by the invention realizes T1、T2Integration of nuclear magnetic resonance imaging, photoacoustic imaging, and drug delivery functions. The biological safety of the obtained nano diagnosis and treatment integrated material is verified at the cellular level and the mouse level, and the nano diagnosis and treatment integrated material has potential application prospect.
Description
Technical Field
The invention relates to the technical field of functional nano materials, in particular to a diagnosis and treatment integrated hollow carbon nano composite material and a preparation method and application thereof.
Background
With the continuous development of new nano-material technology, tumor treatment technology (including chemical drug therapy, gene therapy, photodynamic therapy, photothermal therapy, immunotherapy and the like) and tumor diagnosis method (including nuclear magnetic resonance imaging, photoacoustic imaging, positron emission tomography, computer tomography and the like) are integrated into one material through a modern nano-synthesis technology method, so that the integration of functions is realized, the layered and personalized medical treatment of patients is facilitated, the real-time monitoring of the nano-drug treatment process and the timely feedback of the treatment effect can be facilitated, and the development of the diagnosis and treatment integrated nano-material is one of the development directions of precise medical treatment.
The hollow carbon nanospheres are a type of nano carbon material with the size in the nano range and a hollow structure. Compared with solid carbon nanospheres, the nano-microsphere has lower density, better permeability and unique cavity structure, and can be used as a nano-carrier for delivering drugs. Meanwhile, the special hollow structure of the hollow carbon can promote the fixed-point release of the drugs by methods such as photothermal conversion or ultrasonic waves (such as high-energy focused ultrasound), for example: wang et al report drug loading of hollow carbon and the slow release properties of high energy focused ultrasound drugs (j.am. chem. soc.2015,137,1947-1955), not only that hollow carbon can be used as photoacoustic contrast imaging agent. Therefore, the development of complex functionalization around the hollow carbon nanoball is an important content of the medical-therapeutic integrated research.
Compared with positron emission tomography, computer tomography and other imaging technologies, the magnetic resonance imaging technology is a nondestructive examination technology, can realize two-dimensional cross section imaging and three-dimensional space imaging, and is particularly high in soft tissue resolution. Therefore, the contrast agent with the nuclear magnetic resonance imaging function is integrated into the hollow carbon nanospheres to construct the diagnosis and treatment integrated hollow carbon composite nanomaterial, the integration of the photoacoustic imaging, the nuclear magnetic resonance imaging and the drug delivery function is realized, the complementary advantages in the aspect of diagnosis technology can be realized, the combination of magnetic-mediated drug delivery and photothermal drug delivery can be realized in the aspect of directional drug delivery, and the diagnosis and treatment integrated nano composite nanomaterial is an ideal new diagnosis and treatment integrated nano medicine material.
Patent CN 111494627A discloses a light, heat and magnetic composite material based on hollow carbon spheres, and hollow nano particles UCNPs/Fe coated on the basis of hollow carbon shells3O4@ h-C, interaction of UCNPs and Fe by weak acid and weak base3O4The nano particles are introduced into the hollow carbon spheres to prepare the hollow carbon-coated UCNPs and Fe3O4The synthesized core-shell structure nano particle can meet certain photothermal therapy and imaging diagnosis and treatment integrated requirements, but only a negative contrast agent T is singly used in nuclear magnetic imaging2The detection signal is easy to be confused with the conditions of metal deposition, tissue calcification and the like, and the accuracy of diagnosis is influenced. Meanwhile, considering that the contact effect of the contrast agent and water protons can be influenced by wrapping the contrast agent in the inner cavity, a novel composite material is explored to integrate T1And T2The dual-mode imaging contrast agent is integrated, the full contact exchange with external water protons is guaranteed, the MRI dual-imaging effect is guaranteed while the biological risk is low, the high-efficiency expression is realized at a lesion part, and reliable imaging data are obtained, so that the dual-mode imaging contrast agent is a sufficient and necessary premise for diagnosis and treatment integrated research.
Disclosure of Invention
The invention aims to provide a diagnosis and treatment integrated hollow carbon nano composite material, wherein paramagnetic gadolinium phosphate nano particles and superparamagnetic gamma iron oxide nano particles are integrated in a carbon shell layer of the nano composite material, so that nuclear magnetic resonance T is realized1And T2Integration of imaging technology with photoacoustic imaging and its drug delivery functionality.
The invention also aims to provide a preparation method of the diagnosis and treatment integrated hollow carbon nano composite material, the preparation method provided by the invention takes prefabricated silicon oxide as a core, so that the regulation and control of a hollow structure are easy, phenolic resin is taken as a carbon source, so that the regulation and control of the thickness of a carbon shell layer are easy, a nuclear magnetic resonance contrast agent precursor is loaded by a simple and easy impregnation method, and a one-step carbonization in-situ preparation technology is combined with a conventional etching technology, so that the large-scale production and quality control of the hollow carbon nano composite material are easy.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
the hollow carbon nano composite material integrating diagnosis and treatment is of a spherical hollow core-shell structure and comprises a carbon shell layer, the size of a hollow carbon nano small ball is adjustable within the range of 100-300 nm, the thickness of the shell layer of the hollow carbon is adjustable within the range of 10-70 nm, the carbon shell layer simultaneously contains gadolinium phosphate with paramagnetism and gamma iron oxide nano particles with superparamagnetism, the molar ratio of the gadolinium phosphate to the gamma iron oxide in the carbon shell layer is 1:0.5, and the size of the composite material is within the range of 2-10 nm.
In order to obtain the hollow carbon nano composite material, the preparation technical scheme comprises the following specific steps:
the method comprises the following steps: adding a solution dissolved with a phenolic Resin (RF) to a dispersion of a pre-formed Silica (SiO)2) Stirring and reacting in the solution of nano particles to obtain SiO taking silicon oxide as a core and phenolic resin as a shell2@ RF core-shell nano-spherical particles.
Step two: loading iron and gadolinium precursors to SiO by impregnation2The @ RF core-shell material specifically comprises the following components: iron with equal molar equivalent is dissolvedAnd slowly dripping the ethanol solution of the gadolinium precursor into the ethanol solution of the composite nano spherical particles prepared in the step one, carrying out ultrasonic impregnation, and removing the solvent to obtain the composite nano material.
Step three: the method for preparing the composite functional core-shell material by a one-step carbonization method comprises the following steps: and (4) placing the composite nano material obtained in the step two into a tube furnace, roasting for a period of time at a certain temperature under an inert atmosphere, and obtaining the core-shell type nano composite material taking silicon oxide as a core and taking the gamma ferric oxide and gadolinium phosphate functionalized carbon material as a shell.
Step four: selectively etching to remove the silicon oxide core, which specifically comprises the following steps: preparing a solution with certain concentration for etching silicon oxide, adding the composite material prepared in the third step into the etching solution, soaking for a certain time, centrifugally separating, washing and drying to obtain the diagnosis and treatment integrated hollow carbon nano composite material.
In the first step of the above technical scheme, the solution for dissolving the phenolic resin is one or a combination of two of ethanol, tetrahydrofuran and acetone, wherein: the uniformity of the prepared phenolic resin-coated silicon oxide core-shell structure material is optimal when the resol is adopted and ethanol is used as a solvent, and the concentration is 100-200 mg/L, preferably 150-170 mg/L.
In the first step of the technical scheme, the prefabricated silicon oxide can be directly obtained from a commercial way, the surface of the silicon oxide is not subjected to any chemical modification, and the size of the silicon oxide is determined by the requirement of the size of a cavity of the hollow carbon composite material of the target product.
In the first step of the technical scheme, the obtained SiO is prepared2The adjustment of the shell thickness of the @ RF core-shell nano material can be realized by prolonging the stirring time or increasing the concentration of the phenolic resin or reducing the concentration of the pre-oxidized silicon particles. Preferably, the time of stirring reaction is prolonged and the ethanol solution of the phenolic resin is supplemented.
In the second step of the above technical scheme, the precursor of iron is one of ferric nitrate, ferric chloride, ferric acetate or ferric acetylacetonate, and the precursor of gadolinium is one of gadolinium phosphate and gadolinium phenylphosphate. Preferably, ferric acetylacetonate is used as an iron source, ethanol is used as a solvent, the iron source is firstly loaded by adopting an impregnation loading method, then phenylphosphonic acid is loaded by adopting an impregnation loading method, and finally gadolinium nitrate is loaded.
In the second step of the above technical solution, the precursor of Fe-gd may be a molecular cluster compound containing both of them, preferably [ Fe [ ]6Gd6(μ3-O)2(CO3)(O3PPh)6(O2CtBu)18]And as a precursor, ethanol is used as a solvent, and the loading of the two precursors is realized in one step by adopting an impregnation loading method.
In the second step of the above technical scheme, the environmental temperature of the ultrasonic immersion load is preferably controlled to be 10-25 ℃.
In the second step of the above technical scheme, the solvent is removed by heating and normal temperature evaporation, reduced pressure rotary evaporation, freeze drying evaporation and spray drying, wherein: the spray drying efficiency is high, the freeze drying quality is good, and the reduced pressure rotary evaporation universality is good.
In the third step of the above technical solution, the inert atmosphere may be any gas that has no oxidizing property, no reducing property, and no reaction with the material, wherein: preferably, high purity nitrogen or argon is used, and high purity nitrogen is most economical.
In the third step of the technical scheme, the carbonization temperature is 500-800 ℃, the temperature is lower than 500 ℃, the relative nano metal compound does not reach the crystallization degree, the temperature is higher than 800 ℃, and the nano metal compound is seriously agglomerated and is accompanied with the redox reaction of iron oxide. The carbonization temperature is preferably 550 to 650 ℃.
In the third step of the above technical scheme, the carbonization time is 0.5-1.5 hours, preferably 1 hour, and the gas flow rate is 50-150 mL/min–1At 90 mL/min–1Preferably, the heating rate is 1-5 deg.C/min–1At 3 ℃ min–1。
In the third step of the above technical scheme, the carbonization equipment can be any one of a tube furnace, a kiln and a converter, preferably the tube furnace.
In the fourth step of the above technical scheme, the etching solution for removing the silicon oxide by etching is one of hydrofluoric acid, sodium hydroxide or potassium hydroxide, and the effect of the sodium hydroxide is better; the concentration is 1-3 mol/L, 2mol/L is the best, the etching time is 30-180 minutes, and the specific time is related to the concentration of the etching solution, namely: if the concentration of the etching solution increases, the etching time needs to be reduced correspondingly.
The diagnosis and treatment integrated hollow carbon nano composite material provided by the invention has the nuclear magnetic resonance imaging performance, the photoacoustic imaging performance and the drug carrying performance.
The invention provides a diagnosis and treatment integrated hollow carbon nano composite material, which has the nuclear magnetic resonance imaging performance and is specifically represented by T when the external field intensity is 3.0T1And T2The relaxation number of the weighted imaging has a dependency on the gadolinium phosphate particle size, and when the gadolinium phosphate particle size is about 5nm, T is1The relaxation value of the weighted imaging is 3-4 mM-1·s-1Range, which is embodied as a brightness brightening of the image on the imaged picture; when the size of gamma iron oxide is about 5nm, T2The relaxation value of the weighted imaging is 160-260 mM-1·s-1Range, embodied as a dimming of image brightness on an imaged picture.
The invention provides a diagnosis and treatment integrated hollow carbon nano composite material, which has photoacoustic imaging performance and is characterized in that photoacoustic signals are enhanced and image brightness is increased after the composite material is injected into subcutaneous tumors.
The diagnosis and treatment integrated hollow carbon nano composite material has the drug carrying performance, and is specifically represented by taking an anti-tumor drug adriamycin as an example, the loading amount of the material provided by the invention is 190-390 mg/g, and the specific numerical values are influenced by the hollow size of a sample, the thickness of a shell layer and the amounts of gadolinium phosphate and gamma ferric oxide in the shell layer.
The diagnosis and treatment integrated hollow carbon nano composite material provided by the invention has lower in vitro cytotoxicity and good in vivo biocompatibility and metabolizability.
The diagnosis and treatment integrated hollow carbon nano composite material provided by the invention has the beneficial effects or has the main advantages compared with the prior art:
(1) the invention provides a hollow carbon nano composite material for the first time, and realizes the combination of nuclear magnetic imaging, photoacoustic imaging and drug loading functions.
(2) The invention provides a hollow carbon nano composite material, wherein contrast agent nanoparticles are paramagnetic gadolinium phosphate and superparamagnetic gamma iron oxide which are uniformly embedded in a hollow carbon shell layer, and have good biological safety.
(3) The hollow carbon nano composite material provided by the invention has the advantages that the size of the cavity, the thickness of the carbon layer and the charge of the nuclear magnetic imaging reagent are easy to regulate and control through the provided preparation method, and the possibility is provided for patient layering and personalized medical treatment in the diagnosis and treatment integrated concept.
Drawings
FIG. 1 is a scanning electron microscope and a transmission electron microscope image of five-sized hollow carbon nanocomposites prepared in examples 1-5.
FIG. 2 is an elemental distribution diagram of a hollow carbon nanocomposite prepared with a cavity size of 120nm and a shell thickness of 34 nm.
FIG. 3 is a high-resolution TEM image of the prepared hollow carbon nanocomposite material with a cavity size of 70nm and a shell thickness of 12 nm.
FIG. 4 is an in vitro nuclear magnetic image of three different sizes of hollow carbon nanocomposites prepared in examples 1-3.
FIG. 5 is an intratumoral photoacoustic image of a hollow carbon nanocomposite material with a cavity size of 70nm and a shell thickness of 12 nm.
FIG. 6 shows drug loading of a hollow carbon nanocomposite having a cavity size of 70nm and a shell thickness of 12 nm.
FIG. 7 is the in vitro cytotoxicity of a hollow carbon nanocomposite with a cavity size of 70nm and a shell thickness of 12 nm.
FIG. 8 is a comparison of the hollow carbon nanocomposite in vivo organ section and the blank sample, wherein the hollow carbon nanocomposite has a cavity size of 200nm and a shell thickness of 60 nm.
Detailed Description
In order to clearly understand the technical contents of the present invention, the following examples are given in detail.
Example 1
1) The specific process is as follows: commercial SiO to be purchased2(70-80nm)10mg was dispersed in 50mL of an ethanol solution, and after stirring at room temperature for 1 hour, 0.6g of a 160mg/mL Resol (RF) solution was added. After stirring for 24 hours, the mixture was transferred to a 80mL reaction vessel and subjected to hydrothermal reaction at 100 ℃ for 24 hours. Cooling to room temperature, centrifugally washing the obtained sample, and drying in an oven at 60 ℃ for 12h to obtain SiO2@ RF Polymer beads.
2) Mixing 6mg { Fe6Gd6P6Ultrasonic dissolution into 2mL of an ethanol solution, and addition of 20mg of SiO thereto2@ RF, ultrasonic dispersion in ethanol solution. The mixed solution is stirred and evaporated to dryness at room temperature to obtain SiO2@RF-{Fe6Gd6P6-composite material.
3) Placing the obtained material in a tubular furnace, roasting at 600 ℃ for 1h, wherein the nitrogen flow is 90 mL/min–1At a rate of 3 ℃ min–1And obtaining the Fe-Gd/carbon bead composite material.
4) Then the obtained material is put into 2M NaOH solution to remove SiO by etching2Obtaining the Fe-Gd functionalized hollow carbon spheres. As shown in figure 1.
The following specific examples 2-11 were prepared in the same manner as example 1, and the specific process parameters are shown in Table 1.
Table 1 examples 2-6 specific process parameters
Table 2 examples 7-11 specific process parameters
The resulting product was tested and tested as follows:
FIG. 1 is an electron micrograph of samples of examples 1 to 5, which shows a hollow carbon nanocomposite material having a cavity size of 70 to 80nm and a wall thickness of 12 to 15 nm; a hollow carbon nano composite material with the cavity size of 120-130nm and the wall thickness of 30-35 nm; a hollow carbon nano composite material with the cavity size of 200-210nm and the wall thickness of 60-70 nm; a hollow carbon nano composite material with the cavity size of 120-130nm and the wall thickness of 10-15 nm; a hollow carbon nanocomposite material having a cavity size of 120-130nm and a wall thickness of 60-70 nm.
FIG. 2 is an electron micrograph of the sample of example 2 taken with a Tecnai G2F 20S-Twin type field emission transmission electron microscope. The sample is prepared by ultrasonically dispersing the material in an ethanol solution for 10 minutes, and then dropping the material on a copper net or a nickel net to be dried for testing. An element distribution-plane scan (EDS-mapping) is obtained from the test.
Fig. 3 is a high-resolution transmission electron micrograph of the hollow carbon nanocomposite of the sample of example 1. The sample is prepared by ultrasonically dispersing the material in an ethanol solution for 10 minutes, and then dropping the material on a copper net or a nickel net to be dried for testing. High resolution transmission electron micrographs were obtained by focusing and tilting the sample in a region of high contrast under the electron microscope.
FIG. 4 shows relaxation times T of samples of examples 1, 2 and 31And T2Was measured on a 3.0T nuclear magnetic imager (Siemens prism 3T MRI Scanner, Erlangen, Germany) at room temperature. In the determination of T1And T2In time, samples were prepared as aqueous solutions of different concentrations. T is1And T2The determination of (a) is carried out by an Inversion Recovery (IR) sequence and a CPMG sequence respectively; t is1And T2Weighted MRI images are acquired on the same instrument by a Spin Echo (SE) sequence and a Fast Spin Echo (FSE) sequence, respectively.
In addition, the in vivo photoacoustic imaging of the samples of example 1 was determined by injecting the nanocomposite material subcutaneously intratumorally in a commercial Vevo LAZR PA imaging instrument (Fujifilm visual modalities inc., Toronto, Canada) and continuously acquiring PA images covering the subcutaneous tumor area at different time points (pre, 0, 1, 4, and 24 hours) as shown in fig. 5.
Cytotoxicity of the samples of example 1 was tested by the CCK-8 method as follows: HeLa cells were trypsinized and seeded in 96-well plates at 37 ℃ with 5% CO2Incubation was carried out for 24h under the conditions, and samples of example 1 were added at different concentrations, respectively, and incubation was continued for 4 h. Then, 10. mu.L of a dilution of CCK-8 medium was added to each well, the well plate was returned to an incubator at 37 ℃ for further incubation for about 2 hours, and viable cells were stained with CCK-8, and the OD at 450nm of each well was measured with a microplate reader (TECAN, Infinite M200, Germany), and the cell survival rate was calculated according to the following formula: the cell survival rate (%) (average absorption value of experimental group/average absorption value of control group) × 100%, the results are shown in fig. 6.
The sample of example 1 was vacuum activated at 200 ℃ for 10h before loading the drug doxorubicin hydrochloride (DOX) to remove the adsorbed material in the channels. 30mg of the obtained activated sample was dispersed in 2mL (1 mg. multidot.ml)–1) Then the mixture was stirred at room temperature for 12 hours in the dark. And finally, centrifugally separating, washing and collecting all upper-layer solutions of the material for UV-Vis analysis, measuring the absorbance value at 481nm, and combining the concentration of the DOX solution before drug loading according to a DOX standard curve to obtain the drug loading rate of the material. The steps are repeated until the adsorption saturation drug loading rate (%) of the material to doxorubicin hydrochloride is (drug content in drug-loaded nanoparticles/total amount of drug-loaded nanoparticles) × 100%, and the structure is shown in fig. 7.
In vivo experimental tissue slice testing of the samples of example 3, the procedure was as follows: taking the tissue viscera of nude mice 24h after the injection of the nano composite material, washing the viscera with normal saline or PBS, fixing the viscera in 4% paraformaldehyde, dehydrating and transparentizing, dipping in wax, embedding, trimming, slicing, sticking, fishing out the slices, baking the slices, dewaxing to water, dyeing, dehydrating, sealing, and taking a picture, wherein the picture is obtained as shown in figure 8.
It will be appreciated by persons skilled in the art that the embodiments of the invention described above and shown in the drawings are given by way of example only and are not limiting of the invention. The embodiments described above are described to facilitate an understanding and use of the invention by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make improvements and modifications within the scope of the present invention based on the disclosure of the present invention.
Claims (10)
1. The diagnosis and treatment integrated hollow carbon nano composite material is characterized by being of a spherical hollow core-shell structure and comprising a carbon shell layer, wherein the carbon shell layer simultaneously contains gadolinium phosphate with paramagnetism and gamma iron oxide nanoparticles with superparamagnetism.
2. The diagnosis and treatment integrated hollow carbon nanocomposite material according to claim 1, wherein the size of the composite material is 100-300 nm, and the thickness of the shell layer of the carbon shell layer is 10-60 nm.
3. The diagnosis and treatment integrated hollow carbon nanocomposite material according to claim 1, wherein the molar ratio of gadolinium phosphate to gamma iron oxide in the carbon shell layer is 1:0.5, and the size of gadolinium phosphate to gamma iron oxide is 2-10 nm.
4. The preparation method of the diagnosis and treatment integrated hollow carbon nanocomposite material according to claim 1, comprising the following specific steps:
the method comprises the following steps: adding a solution dissolved with a phenolic Resin (RF) to a dispersion of a pre-formed Silica (SiO)2) Stirring and reacting in the solution of nano particles to obtain SiO taking silicon oxide as a core and phenolic resin as a shell2@ RF core-shell nanosphere particles;
step two: loading iron and gadolinium precursors to SiO by impregnation2@ RF core-shell materialFeeding, specifically comprising: slowly dripping ethanol solution dissolved with equal molar equivalent of ferrum and gadolinium precursors into the SiO prepared in the step one2The @ RF nuclear shell nano spherical particles are ultrasonically immersed in an ethanol solution, and the solvent is evaporated by decompression and rotation to obtain the composite nano material;
step three: the method for preparing the composite functional core-shell material by a one-step carbonization method comprises the following steps: placing the composite nano-material obtained in the step two in a tube furnace, roasting for a period of time at a certain temperature under an inert atmosphere to obtain a core-shell type nano-composite material taking silicon oxide as a core and taking a gamma ferric oxide and gadolinium phosphate functionalized carbon material as a shell;
step four: selectively etching to remove the silicon oxide core, which specifically comprises the following steps: preparing a solution with certain concentration for etching silicon oxide, adding the core-shell type nano composite material prepared in the third step into the etching solution, soaking for a certain time, centrifugally separating, washing and drying to obtain the diagnosis and treatment integrated hollow carbon nano composite material.
5. The method for preparing the diagnosis and treatment integrated hollow carbon nanocomposite material according to claim 4, wherein the solution for dissolving the phenolic resin is one or a combination of two of ethanol, tetrahydrofuran and acetone, and the concentration of the phenolic resin in the solution is 100-200 mg/L.
6. The method according to claim 4, wherein the precursor of iron is one of ferric nitrate, ferric chloride, ferric acetate or ferric acetylacetonate, and the precursor of gadolinium is one of gadolinium phosphate and gadolinium phenylphosphate.
7. The preparation method of the diagnosis and treatment integrated hollow carbon nanocomposite material according to claim 4, wherein the precursor of iron and gadolinium is a molecular cluster compound of iron and gadolinium, and the specific molecular formula is as follows: [ Fe ]6Gd6(μ3-O)2(CO3)(O3PPh)6(O2CtBu)18]。
8. The method for preparing a diagnosis and treatment integrated hollow carbon nanocomposite material according to claim 4, wherein the inert atmosphere can be high-purity nitrogen or argon, the carbonization temperature during roasting is 500-800 ℃, the carbonization time is 0.5-1.5 hours, and the gas flow rate is 50-150 mL/min–1The temperature rise rate is 1-5 ℃ per minute–1In the meantime.
9. The preparation method of the diagnosis and treatment integrated hollow carbon nanocomposite material according to claim 4, wherein the etching solution for removing silicon oxide by etching is one of hydrofluoric acid, sodium hydroxide or potassium hydroxide, the concentration of the etching solution is 1-3 mol/L, and the etching time is 30-180 minutes.
10. A theranostic hollow carbon nanocomposite material as claimed in any one of claims 1 to 3 at T1And T2-weighted contrast nuclear and photoacoustic imaging and drug delivery.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010105058A1 (en) * | 2009-03-11 | 2010-09-16 | Northeastern University | Low-aspect ratio nanostructures |
| CN105561345A (en) * | 2016-01-26 | 2016-05-11 | 东华大学 | Preparation method of hollow mesoporous silica loaded by nanometer star-shaped gold particles |
| CN106668878A (en) * | 2017-01-08 | 2017-05-17 | 复旦大学 | Multifunctional mesoporous carbon microsphere integrated with T1-T2 dual mode and preparation method thereof |
| CN108598395A (en) * | 2018-03-30 | 2018-09-28 | 武汉理工大学 | The magnanimity preparation method of monodisperse silica/nitrogen-doped carbon composite Nano ball or microballoon |
| CN111494627A (en) * | 2020-05-09 | 2020-08-07 | 潍坊科技学院 | Preparation method and application of light, heat and magnetic composite material based on hollow carbon spheres |
-
2020
- 2020-09-28 CN CN202011044117.1A patent/CN112168983B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010105058A1 (en) * | 2009-03-11 | 2010-09-16 | Northeastern University | Low-aspect ratio nanostructures |
| CN105561345A (en) * | 2016-01-26 | 2016-05-11 | 东华大学 | Preparation method of hollow mesoporous silica loaded by nanometer star-shaped gold particles |
| CN106668878A (en) * | 2017-01-08 | 2017-05-17 | 复旦大学 | Multifunctional mesoporous carbon microsphere integrated with T1-T2 dual mode and preparation method thereof |
| CN108598395A (en) * | 2018-03-30 | 2018-09-28 | 武汉理工大学 | The magnanimity preparation method of monodisperse silica/nitrogen-doped carbon composite Nano ball or microballoon |
| CN111494627A (en) * | 2020-05-09 | 2020-08-07 | 潍坊科技学院 | Preparation method and application of light, heat and magnetic composite material based on hollow carbon spheres |
Non-Patent Citations (2)
| Title |
|---|
| AHMED O. ELZOGHBY ET AL: "Hybrid protein-inorganic nanoparticles: From tumor-targeted drug delivery to cancer imaging", 《JOURNAL OF CONTROLLED RELEASE》 * |
| 朱脉勇 等: "四氧化三铁纳米材料的制备与应用", 《化学进展》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113697861A (en) * | 2021-08-11 | 2021-11-26 | 上海交通大学 | Composite material and preparation method and application thereof |
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