CN114099467A - Magnetic induction medium fever sustained-release method for tumor treatment - Google Patents
Magnetic induction medium fever sustained-release method for tumor treatment Download PDFInfo
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Abstract
The present invention belongs to the field of tumor treatmentThe technical field of treatment, discloses a magnetic induction medium fever slow-release method for tumor treatment, which comprises the following steps: s1, preparing composite magnetic nanoparticles loaded with tumor therapeutic drugs, and sequentially coating a slow release layer and a cell membrane layer on the surfaces of the nanoparticles to obtain a product A; s2, dissolving the product A in a target cell culture solution, and uniformly dispersing the culture solution by using ultrasonic waves to obtain a product B; s3, injecting the product B into a blood supply vessel of the tumor by using an intervention technology, providing an orthogonal magnetic field and near-infrared illumination in vitro, and enabling the tumor to be in an orthogonal magnetic field and near-infrared illumination area; wherein the composite magnetic nanoparticles comprise Fe3O4The tumor treatment medicine is more than one of adriamycin, paclitaxel and cisplatin; in conclusion, the magnetic induction medium can reach the affected part in a targeted way under the action of a magnetic field, and then the effective slow release of the tumor treatment medicine is realized through magnetothermal and photothermal under the irradiation of an orthogonal magnetic field and near infrared light.
Description
Technical Field
The invention belongs to the technical field of tumor treatment, and particularly relates to a magnetic induction medium heating sustained-release method for tumor treatment.
Background
Cancer, as a serious disease threatening the life and health of human beings, has the characteristics of low cure rate, relapse and high death rate for a long time.
The main means and methods for treating cancer at present comprise surgery, radiotherapy and chemotherapy, but all of the methods have great risks, are easy to cause great trauma and complications to patients, and are easy to cause great damage to normal cells when cancer cells are killed.
With the research and development of tumor treatment technology, a treatment scheme for transferring drugs by using drug carriers appears, but the scheme has the problems of poor biocompatibility and insufficiently accurate administration position in actual use, limits the drug transfer efficiency to tumor tissues to a certain extent, and influences the treatment effect.
Disclosure of Invention
In view of the above, the present invention provides a method for uniformly and slowly releasing a liquid magnetic induction medium for tumor therapy.
In order to achieve the purpose, the invention provides the following technical scheme: a slow-release method of magnetic induction medium fever for treating tumor comprises the following steps:
s1, preparing composite magnetic nanoparticles loaded with tumor therapeutic drugs, and sequentially coating a slow release layer and a cell membrane layer on the surfaces of the nanoparticles to obtain a product A;
s2, dissolving the product A in a target cell culture solution, and uniformly dispersing the culture solution by using ultrasonic waves to obtain a product B;
s3, injecting the product B into a blood supply vessel of the tumor by using an interventional technique, providing an orthogonal magnetic field and near infrared illumination in vitro, and enabling the tumor to be in an orthogonal magnetic field and near infrared illumination area.
Preferably, the composite magnetic nanoparticles comprise Fe3O4Nanosphere and porousThe nano carbon fiber, the tumor treatment medicine is more than one of adriamycin, paclitaxel and cisplatin.
Preferably, in step S1, the preparing of the composite magnetic nanoparticles loaded with the tumor therapeutic drug includes:
mixing Fe3O4Mixing and dispersing the nano microspheres and the porous carbon nanofibers into normal saline or phosphoric acid buffer solution to obtain matrix dispersion liquid;
preparing an aqueous solution of the tumor treatment drug, ultrasonically mixing the aqueous solution with the matrix dispersion liquid, standing for 6-24 h, and then carrying out centrifugal cleaning and freeze drying to obtain the composite magnetic nanoparticles loaded with the tumor treatment drug.
Preferably, said Fe3O4The mixing ratio of the nano microspheres to the porous carbon nanofibers is 1: 1 to 3.
Preferably, said Fe3O4The nano-microsphere is of a double-layer structure, and the double-layer structure comprises a layer of Fe3O4A core layer and a graphene wall layer.
Preferably, the graphene wall layer is coated on Fe through electrostatic interaction3O4The surface of the nuclear layer.
Preferably, the porous carbon nanofiber is of a multilayer structure, the multilayer structure comprises a carbon nanofiber core layer, at least one chitosan wall layer and at least one sodium alginate wall layer, and the chitosan wall layer and the sodium alginate wall layer are distributed in a staggered mode.
Preferably, the slow release layer is formed by mixing and coating chitosan and Arabic gum, the surface wall of the cell membrane layer is provided with cracks, and the cracks are formed by ultrasonic disruption.
Preferably, in step S1, the coating of the cell membrane layer on the surface of the particle includes:
mixing the compound magnetic nanoparticles loaded with the tumor treatment drug with a culture medium in which cells are uniformly dispersed, incubating for 1.5-2 h, and then treating a reaction solution by using an ultrasonic cell crusher;
and magnetically separating and collecting the separated solid product, and washing the solid product to obtain the composite magnetic nanoparticles which are coated with the cell membrane layer and load the tumor treatment drugs.
Preferably, in the step S2, the power of the ultrasonic dispersion is 500-1000W, the ultrasonic frequency is 10-40 KHz, and the ultrasonic time is 0.2-0.5 h.
Compared with the prior art, the invention has the following beneficial effects:
in the present invention, Fe3O4Mixing nanometer microsphere and porous nanometer carbon fiber as raw materials to form composite magnetic nanoparticles, wherein Fe3O4The nano-microsphere comprises a layer of Fe3O4The porous carbon nanofiber has a multilayer structure comprising a carbon nanofiber core layer, at least one chitosan wall layer and a sodium alginate wall layer which are distributed in a staggered mode, and specifically, the graphene and the carbon nanofiber have good photo-thermal property, and the graphene and the Fe have good photo-thermal property3O4The magnetic induction medium can reach the affected part in a targeted way under the action of a magnetic field, and then the effective slow release of the tumor treatment medicine is realized through magnetic heat and photo-heat under the irradiation of an orthogonal magnetic field and near infrared light.
In addition, the surface of the composite magnetic nanoparticle is also coated with a cell membrane layer, the cell membrane layer can effectively improve the drug invisibility, and the surface wall of the cell membrane layer is provided with cracks, so that the cracks can be enlarged under the principle of heat and cold contraction, and the slow release speed of the tumor treatment drug can be effectively controlled.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A slow-release method of magnetic induction medium fever for treating tumor comprises the following steps:
s1, preparing composite magnetic nanoparticles loaded with tumor therapeutic drugs, and sequentially coating a slow release layer and a cell membrane layer on the surfaces of the nanoparticles to obtain a product A;
specifically, in this step
Preparing composite magnetic nanoparticles:
by electrostatic interaction at Fe3O4The surface of the nuclear layer is coated with a graphene wall layer to form Fe3O4And (4) nano microspheres. In Fe3O4In the nano-microsphere, Fe3O4The nuclear layer has good magnetic compliance and magnetocaloric property, and the graphene has good photo-thermal property, so that Fe is generated3O4The nanometer microsphere can achieve the effect of cooperative control of magnetocaloric and photothermal.
At least one chitosan wall layer and at least one sodium alginate wall layer are coated on the surface of a carbon nanofiber core layer in a staggered manner through electrostatic action, so that the porous carbon nanofiber with good photo-thermal property is formed.
According to the following steps: 1 mixing ratio of Fe3O4Mixing and dispersing the nano microspheres and the porous carbon nanofibers into normal saline or phosphoric acid buffer solution to obtain matrix dispersion liquid.
Preparing a water solution of the tumor treatment drug, mixing the water solution with the matrix dispersion liquid by ultrasonic, standing for 6 hours, and then obtaining the composite magnetic nanoparticles loaded with the tumor treatment drug by centrifugal cleaning and freeze drying. Wherein the tumor therapeutic medicine is more than one of adriamycin, paclitaxel and cisplatin.
Preparing a mixed solution of chitosan and Arabic gum, ultrasonically dispersing the composite magnetic nanoparticles loaded with the tumor therapeutic drugs into the mixed solution, magnetically separating and collecting a separated solid product a, wherein the solid product a is the composite magnetic nanoparticles loaded with the tumor therapeutic drugs, the surfaces of which are coated with a slow release layer.
Mixing the solid product a with a culture medium in which cells are uniformly dispersed, incubating for 1.5h, and treating a reaction solution by using an ultrasonic cell crusher; and magnetically separating and collecting the separated solid product b, and washing the solid product b to obtain the composite magnetic nanoparticles which are sequentially coated with the sustained-release layer and the cell membrane layer and load the tumor treatment drugs on the surface.
S2, intermittently sterilizing the product A, dissolving the product A in a target cell culture solution, and uniformly dispersing the culture solution by using ultrasonic waves to obtain a product B; wherein: the ultrasonic dispersion power is 1000W, the ultrasonic frequency is 40KHz, and the ultrasonic time is 0.2 h.
S3, injecting the product B into a blood supply vessel of the tumor by using an interventional technique, providing an orthogonal magnetic field and near infrared illumination in vitro, and enabling the tumor to be in an orthogonal magnetic field and near infrared illumination area.
Example 2
A slow-release method of magnetic induction medium fever for treating tumor comprises the following steps:
s1, preparing composite magnetic nanoparticles loaded with tumor therapeutic drugs, and sequentially coating a slow release layer and a cell membrane layer on the surfaces of the nanoparticles to obtain a product A;
specifically, in this step
Preparing composite magnetic nanoparticles:
by electrostatic interaction at Fe3O4The surface of the nuclear layer is coated with a graphene wall layer to form Fe3O4And (4) nano microspheres. In Fe3O4In the nano-microsphere, Fe3O4The nuclear layer has good magnetic compliance and magnetocaloric property, and the graphene has good photo-thermal property, so that Fe is generated3O4The nanometer microsphere can achieve the effect of cooperative control of magnetocaloric and photothermal.
At least one chitosan wall layer and at least one sodium alginate wall layer are coated on the surface of a carbon nanofiber core layer in a staggered manner through electrostatic action, so that the porous carbon nanofiber with good photo-thermal property is formed.
According to the following steps: 2 mixing ratio of Fe3O4Mixing and dispersing the nano microspheres and the porous carbon nanofibers into normal saline or phosphoric acid buffer solution to obtain matrix dispersion liquid.
Preparing a water solution of the tumor treatment drug, mixing the water solution with the matrix dispersion liquid by ultrasonic, standing for 12 hours, and then obtaining the composite magnetic nanoparticles loaded with the tumor treatment drug by centrifugal cleaning and freeze drying. Wherein the tumor therapeutic medicine is more than one of adriamycin, paclitaxel and cisplatin.
Preparing a mixed solution of chitosan and Arabic gum, ultrasonically dispersing the composite magnetic nanoparticles loaded with the tumor therapeutic drugs into the mixed solution, magnetically separating and collecting a separated solid product a, wherein the solid product a is the composite magnetic nanoparticles loaded with the tumor therapeutic drugs, the surfaces of which are coated with a slow release layer.
Mixing the solid product a with a culture medium in which cells are uniformly dispersed, incubating for 1.8h, and treating a reaction solution by using an ultrasonic cell crusher; and magnetically separating and collecting the separated solid product b, and washing the solid product b to obtain the composite magnetic nanoparticles which are sequentially coated with the sustained-release layer and the cell membrane layer and load the tumor treatment drugs on the surface.
S2, intermittently sterilizing the product A, dissolving the product A in a target cell culture solution, and uniformly dispersing the culture solution by using ultrasonic waves to obtain a product B; wherein: the power of ultrasonic dispersion is 750W, the ultrasonic frequency is 20KHz, and the ultrasonic time is 0.3 h.
S3, injecting the product B into a blood supply vessel of the tumor by using an interventional technique, providing an orthogonal magnetic field and near infrared illumination in vitro, and enabling the tumor to be in an orthogonal magnetic field and near infrared illumination area.
Example 3
A slow-release method of magnetic induction medium fever for treating tumor comprises the following steps:
s1, preparing composite magnetic nanoparticles loaded with tumor therapeutic drugs, and sequentially coating a slow release layer and a cell membrane layer on the surfaces of the nanoparticles to obtain a product A;
specifically, in this step
Preparing composite magnetic nanoparticles:
by electrostatic interaction at Fe3O4The surface of the nuclear layer is coated with a graphene wall layer to form Fe3O4And (4) nano microspheres. In Fe3O4In the nano-microsphere, Fe3O4The nuclear layer has good magnetic compliance and magnetocaloric property, and the graphene has good photo-thermal property, so that Fe is generated3O4The nanometer microsphere can achieve the effect of cooperative control of magnetocaloric and photothermal.
At least one chitosan wall layer and at least one sodium alginate wall layer are coated on the surface of a carbon nanofiber core layer in a staggered manner through electrostatic action, so that the porous carbon nanofiber with good photo-thermal property is formed.
According to the following steps: 3 mixing ratio of Fe3O4Mixing and dispersing the nano microspheres and the porous carbon nanofibers into normal saline or phosphoric acid buffer solution to obtain matrix dispersion liquid.
Preparing a water solution of the tumor treatment drug, mixing the water solution with the matrix dispersion liquid by ultrasonic, standing for 24 hours, and then obtaining the composite magnetic nanoparticles loaded with the tumor treatment drug by centrifugal cleaning and freeze drying. Wherein the tumor therapeutic medicine is more than one of adriamycin, paclitaxel and cisplatin.
Preparing a mixed solution of chitosan and Arabic gum, ultrasonically dispersing the composite magnetic nanoparticles loaded with the tumor therapeutic drugs into the mixed solution, magnetically separating and collecting a separated solid product a, wherein the solid product a is the composite magnetic nanoparticles loaded with the tumor therapeutic drugs, the surfaces of which are coated with a slow release layer.
Mixing the solid product a with a culture medium in which cells are uniformly dispersed, incubating for 2h, and treating a reaction solution by using an ultrasonic cell crusher; and magnetically separating and collecting the separated solid product b, and washing the solid product b to obtain the composite magnetic nanoparticles which are sequentially coated with the sustained-release layer and the cell membrane layer and load the tumor treatment drugs on the surface.
S2, intermittently sterilizing the product A, dissolving the product A in a target cell culture solution, and uniformly dispersing the culture solution by using ultrasonic waves to obtain a product B; wherein: the power of ultrasonic dispersion is 550W, the ultrasonic frequency is 12KHz, and the ultrasonic time is 0.5 h.
S3, injecting the product B into a blood supply vessel of the tumor by using an interventional technique, providing an orthogonal magnetic field and near infrared illumination in vitro, and enabling the tumor to be in an orthogonal magnetic field and near infrared illumination area.
Utilize the process that ferric trichloride is reduced to ferrous oxide, inject ferric trichloride solution into the tumour, and evenly distributed, then inject hydrogen peroxide into, hydrogen peroxide makes the in-process that ferric trichloride becomes ferric peroxide, because the protein in the tumour is also oxidized, form the tiny granule of ferric peroxide and tumour tissue protein simultaneously, because ferric trichloride or hydrogen peroxide contain the chemotherapy medicine, in the in-process of the tiny granule of ferric peroxide and tumour tissue protein (in this in-process because tumour tissue is destroyed, play the effect of killing the tumour), the medicine is also wrapped up wherein, can slowly release and continue remaining tumour tissue, iron is wherein, can regard as the target material of magnetic field treatment, make it generate heat and play the effect of thermotherapy.
The following steps:
the chemotherapeutic agent may be a chemical agent, any approved agent, or potentially approved agent;
the chemotherapy drug can also be radioactive isotope (such as I125, I131, yi90), and the chemotherapy drug is embedded in tumor, can play a role of radiotherapy, and can also be matched with magnetic field thermotherapy of iron for mutual complementation, so as to improve the overall curative effect;
the chemotherapy drug can also be biological drug or alkaloid, nucleic acid substance, hapten for immunization, etc.; the chemotherapeutic medicine is embedded in tumor, and can be biologically modified to modify tumor antigen, and then released into lymph or blood to achieve tumor immunity effect.
The reducing agent can be ferric trichloride and can also be any reduced substance; the oxidizing agent is hydrogen peroxide, but also other substances which can be oxidized. The reducing agent and the oxidizing agent can be respectively injected into the tumor, or can be mixed firstly and then injected into the tumor tissue.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (10)
1. A slow-release method for magnetic induction medium fever for tumor treatment is characterized by comprising the following steps:
s1, preparing composite magnetic nanoparticles loaded with tumor therapeutic drugs, and sequentially coating a slow release layer and a cell membrane layer on the surfaces of the nanoparticles to obtain a product A;
s2, dissolving the product A in a target cell culture solution, and uniformly dispersing the culture solution by using ultrasonic waves to obtain a product B;
s3, injecting the product B into a blood supply vessel of the tumor by using an interventional technique, providing an orthogonal magnetic field and near infrared illumination in vitro, and enabling the tumor to be in an orthogonal magnetic field and near infrared illumination area.
2. The slow-release method for the fever with magnetic induction medium for the treatment of tumor according to claim 1, which is characterized in that: the composite magnetic nanoparticles comprise Fe3O4The tumor treatment medicine is more than one of adriamycin, paclitaxel and cisplatin.
3. The sustained-release method for tumor therapy by using a magnetically-induced medium to generate heat according to claim 2, wherein in step S1, the preparation of the composite magnetic nanoparticles loaded with tumor-therapy drugs comprises:
mixing Fe3O4Mixing and dispersing the nano microspheres and the porous carbon nanofibers into normal saline or phosphoric acid buffer solution to obtain matrix dispersion liquid;
preparing an aqueous solution of the tumor treatment drug, ultrasonically mixing the aqueous solution with the matrix dispersion liquid, standing for 6-24 h, and then carrying out centrifugal cleaning and freeze drying to obtain the composite magnetic nanoparticles loaded with the tumor treatment drug.
4. The sustained-release method for fever with magnetic induction medium used for tumor therapy according to claim 3, characterized in that: said Fe3O4The mixing ratio of the nano microspheres to the porous carbon nanofibers is 1: 1 to 3.
5. The slow-release method for tumor therapy based on the induction heating medium of claim 3 or 4, wherein the Fe is Fe3O4The nano-microsphere is of a double-layer structure, andthe double-layer structure comprises a layer of Fe3O4A core layer and a graphene wall layer.
6. The sustained-release method for fever with magnetic induction medium of claim 5, which is characterized in that: the graphene wall layer is coated on Fe through electrostatic action3O4The surface of the nuclear layer.
7. The method for sustained release of fever with magnetically induced media for the treatment of tumors as claimed in claim 3 or 4, wherein the porous filamentous nanocarbon is a multi-layered structure, and the multi-layered structure comprises a core layer of filamentous nanocarbon, at least one chitosan wall layer and at least one sodium alginate wall layer, and the chitosan wall layer and the sodium alginate wall layer are distributed in a staggered manner.
8. The slow-release method for the fever with magnetic induction medium for the treatment of tumor according to claim 1, which is characterized in that: the slow release layer is formed by mixing and coating chitosan and Arabic gum, the surface wall of the cell membrane layer is provided with cracks, and the cracks are formed by ultrasonic crushing.
9. The sustained-release method for tumor therapy with heating mediated by a magnetically sensitive medium according to claim 8, wherein the step S1 includes:
mixing the compound magnetic nanoparticles loaded with the tumor treatment drug with a culture medium in which cells are uniformly dispersed, incubating for 1.5-2 h, and then treating a reaction solution by using an ultrasonic cell crusher;
and magnetically separating and collecting the separated solid product, and washing the solid product to obtain the composite magnetic nanoparticles which are coated with the cell membrane layer and load the tumor treatment drugs.
10. The method for uniformly and slowly releasing the liquid magnetically-inductive medium used for treating the tumors as claimed in claim 1, wherein: in the step S2, the power of ultrasonic dispersion is 500-1000W, the ultrasonic frequency is 10-40 KHz, and the ultrasonic time is 0.2-0.5 h.
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| US20110177153A1 (en) * | 2005-10-25 | 2011-07-21 | Hong Zhu | targeted nanoparticle drug for magnetic hyperthermia treatment on malignant tumors |
| CN107261142A (en) * | 2017-06-05 | 2017-10-20 | 东华大学 | It is a kind of for porous filamentous nanocarbon base load medicine photothermal reagent of oncotherapy and preparation method thereof |
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