CN112386748A - Magnesium alloy nano robot and preparation method thereof - Google Patents
Magnesium alloy nano robot and preparation method thereof Download PDFInfo
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- CN112386748A CN112386748A CN201910740317.1A CN201910740317A CN112386748A CN 112386748 A CN112386748 A CN 112386748A CN 201910740317 A CN201910740317 A CN 201910740317A CN 112386748 A CN112386748 A CN 112386748A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/02—Inorganic materials
- A61L31/022—Metals or alloys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/148—Materials at least partially resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
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- C—CHEMISTRY; METALLURGY
- C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
- C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
- C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
- C23C14/0005—Separation of the coating from the substrate
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- C—CHEMISTRY; METALLURGY
- C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
- C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
- C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
- C23C14/06—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the coating material
- C23C14/14—Metallic material, boron or silicon
- C23C14/16—Metallic material, boron or silicon on metallic substrates or on substrates of boron or silicon
- C23C14/165—Metallic material, boron or silicon on metallic substrates or on substrates of boron or silicon by cathodic sputtering
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- C—CHEMISTRY; METALLURGY
- C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
- C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
- C23C14/00—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material
- C23C14/22—Coating by vacuum evaporation, by sputtering or by ion implantation of the coating forming material characterised by the process of coating
- C23C14/34—Sputtering
- C23C14/35—Sputtering by application of a magnetic field, e.g. magnetron sputtering
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
- A61L2300/604—Biodegradation
Abstract
The invention belongs to the field of nanotechnology, and particularly relates to a magnesium alloy nano robot and a preparation method thereof. The preparation method provided by the invention comprises the following steps: a) plating a Wude alloy on the surface of the substrate to form a Wude alloy film layer; b) plating a magnesium alloy magnetic material on the Wude alloy layer to form a magnesium alloy magnetic film layer; c) heating the multilayer composite material obtained in the step b) until the Wude alloy film layer in the material is melted, and separating the magnesium alloy magnetic film layer from the substrate; d) cutting and shaping the magnesium alloy magnetic film layer obtained by the separation in the step c) to obtain a magnesium alloy magnetic body; e) and mixing the magnesium alloy magnetic body and the anti-inflammatory drug in a solvent, carrying out centrifugal separation, and discarding the supernatant to obtain the magnesium alloy nano robot. The preparation method provided by the invention has stable production process and is suitable for industrialization; the magnesium alloy nano robot prepared by the method has good magnetism, controllable degradation time and no local inflammatory reaction in the degradation process.
Description
Technical Field
The invention belongs to the field of nanotechnology, and particularly relates to a magnesium alloy nano robot and a preparation method thereof.
Background
The nano robot refers to a small robot with the dimension in the nano level, and has very important potential application in the fields of biomedicine, environmental protection and the like, such as minimally invasive surgery, targeted therapy, cell operation, heavy metal detection, pollutant degradation and the like, so the nano robot is widely concerned by researchers at home and abroad and has rapid development in recent years.
The working environment of the nano robot is in an environment with a low Reynolds coefficient, an object can be regarded as moving in a very viscous, tiny and slow environment, the viscous force is dominant, and the inertial force is negligible. Under such conditions, the nano-robot must be constantly powered to drive the nano-robot. However, due to its small size, power sources such as batteries, motors, etc. are difficult to be loaded in the micro-nano robot, and thus, various driving methods of the micro-nano robot have been proposed, including self-driving (electrophoresis driving, diffusion driving, self-thermophoresis driving, bubble driving, etc.) and external field driving (magnetic field, sound field, and light driving). The magnetic field driving mode has a low magnetic field strength, and a low-frequency magnetic field can penetrate through biological tissues and is harmless to organisms, so that the magnetic field driving mode becomes one of the most promising driving modes in the field of nano robots. Therefore, how to prepare the nano robot which is easily driven and controlled by the external magnetic field under the environment of lower reynolds coefficient becomes the focus of research of researchers.
With the development of materials and processes, various magnetic nano robots are continuously appeared, and three times of upgrade evolution from metal nano robots, drug eluting nano robots to biodegradable nano robots are completed. The degradation of the degradable nano metal material can cause a heavier local inflammatory reaction, so that the degradable nano metal material is not a perfect choice of degradable materials, and the degradable metal material can avoid the problems to a certain extent, so that the degradable nano metal material has a better application prospect. The most concerned degradable metal currently belongs to magnesium alloy, the degradable magnesium alloy has good biocompatibility and stronger strength, and can effectively reduce the problems of intimal hyperplasia, thrombus and the like of blood vessels, so that the degradable magnesium alloy is known as a revolutionary metal biological material and has great attention.
At present, most reported methods for preparing the magnetic magnesium alloy nano robot still stay in an experimental stage, and have the problems of unstable production process, difficulty in controlling degradation time, local inflammatory reaction caused in the degradation process and the like.
Disclosure of Invention
In view of the above, the present invention aims to provide a magnesium alloy nano robot and a preparation method thereof, wherein the preparation method provided by the present invention has a stable production process and is suitable for industrialization; the magnesium alloy nano robot prepared by the method has good magnetism, controllable degradation time and no local inflammatory reaction in the degradation process.
The invention provides a preparation method of a magnesium alloy nano robot, which comprises the following steps:
a) plating a Wude alloy on the surface of the substrate to form a Wude alloy film layer;
b) plating a magnesium alloy magnetic material on the Wude alloy layer to form a magnesium alloy magnetic film layer;
c) heating the multilayer composite material obtained in the step b) until the Wude alloy film layer in the material is melted, and separating the magnesium alloy magnetic film layer from the substrate;
d) cutting and shaping the magnesium alloy magnetic film layer obtained by the separation in the step c) to obtain a magnesium alloy magnetic body;
e) and mixing the magnesium alloy magnetic body and the anti-inflammatory drug in a solvent, carrying out centrifugal separation, and discarding the supernatant to obtain the magnesium alloy nano robot.
Preferably, in the step b), the plating mode is magnetron sputtering;
the sputtering rate of the magnetron sputtering is 5-10 nm/s; what is needed isThe magnetron sputtering time is 40-120 s; the vacuum degree of the magnetron sputtering is 5 multiplied by 10-4～3×10-4Pa; the substrate temperature of the magnetron sputtering is 80-100 ℃.
Preferably, in step b), the magnesium alloy magnetic film layer comprises magnesium, zinc, titanium, silicon and ferroferric oxide.
Preferably, in the step b), the thickness of the magnesium alloy magnetic film layer is 10-1000 nm.
Preferably, in step c), the multilayer composite is heated in water; the heating temperature is 75-80 ℃.
Preferably, in the step d), the cutting and shaping manner is laser cutting;
the scanning step of the laser cutting is 10-200 nm/s; the laser spot of the laser cutting is 0.05-0.1 mu m; the energy of the electron beam for laser cutting is 10-100 mJ.
Preferably, in step e), the anti-inflammatory drug comprises one or more of paclitaxel, rapamycin, arsenic trioxide and everolimus.
Preferably, in the step e), the mass ratio of the magnesium alloy magnetic body to the anti-inflammatory drug is 5: (5-20).
Preferably, in the step e), the magnesium alloy magnetic body is dried and sterilized before being mixed with the anti-inflammatory drug.
The invention provides a magnesium alloy nano robot prepared by the preparation method of the technical scheme.
Compared with the prior art, the invention provides a magnesium alloy nano robot and a preparation method thereof. The preparation method of the magnesium alloy nanometer machine provided by the invention comprises the following steps: a) plating a Wude alloy on the surface of the substrate to form a Wude alloy film layer; b) plating a magnesium alloy magnetic material on the Wude alloy layer to form a magnesium alloy magnetic film layer; c) heating the multilayer composite material obtained in the step b) until the Wude alloy film layer in the material is melted, and separating the magnesium alloy magnetic film layer from the substrate; d) cutting and shaping the magnesium alloy magnetic film layer obtained by the separation in the step c) to obtain a magnesium alloy magnetic body; e) and mixing the magnesium alloy magnetic body and the anti-inflammatory drug in a solvent, carrying out centrifugal separation, and discarding the supernatant to obtain the magnesium alloy nano robot. The preparation method provided by the invention selects the magnetic magnesium alloy as the main material of the nano robot, so that the nano robot can show good magnetism; meanwhile, the surface of the magnesium alloy magnetic body is loaded with anti-inflammatory drugs, so that inflammatory reaction induced by degradation of the nano robot can be greatly relieved; in addition, the preparation method can also realize the regulation and control of the degradation rate of the magnesium alloy nano robot by changing the composition and the size of the magnesium alloy magnetic body, thereby controlling the degradation time of the magnesium alloy nano robot. The preparation method provided by the invention has stable and controllable production process and is suitable for industrialization. The experimental results show that: the magnesium alloy nano robot prepared by the method can basically complete degradation within 4-6 months, and cannot cause local inflammatory reaction in the degradation process.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.
FIG. 1 is a schematic diagram illustrating the operation of heating and melting a Wude alloy film according to an embodiment of the present invention;
fig. 2 is a schematic structural view of a magnesium alloy magnetic body according to an embodiment of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the 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.
The invention provides a preparation method of a magnesium alloy nano robot, which comprises the following steps:
a) plating a Wude alloy on the surface of the substrate to form a Wude alloy film layer;
b) plating a magnesium alloy magnetic material on the Wude alloy layer to form a magnesium alloy magnetic film layer;
c) heating the multilayer composite material obtained in the step b) until the Wude alloy film layer in the material is melted, and separating the magnesium alloy magnetic film layer from the substrate;
d) cutting and shaping the magnesium alloy magnetic film layer obtained by the separation in the step c) to obtain a magnesium alloy magnetic body;
e) and mixing the magnesium alloy magnetic body and the anti-inflammatory drug in a solvent, performing centrifugal separation, and removing supernatant to obtain the magnesium alloy nano robot.
In the preparation method provided by the invention, firstly, a substrate base plate is provided, the type of the substrate base plate can be a polyethylene terephthalate (PET) base plate, a Polyimide (PI) base plate, a Polyethylene (PE) base plate or other flexible base plates, and can also be a glass base plate; the shape of the substrate base plate can be rectangular, circular or irregular; the thickness of the substrate base plate is preferably 0.1-5 mm, more preferably 0.2-1 mm, and specifically can be 0.2mm, 0.3mm, 0.4mm, 0.5mm, 0.6mm, 0.7mm, 0.8mm, 0.9mm or 1 mm.
In the preparation method provided by the invention, after the substrate base plate is obtained, the surface of the substrate base plate is plated with the Wude alloy. Before the wude alloy is plated, the surface of the substrate base plate is preferably washed and dried, so that stains on the surface of the substrate base plate are removed, and the influence of the stains on the surface of the substrate base plate on the subsequent process is avoided. In the invention, the plating mode is evaporation; the Wude alloy target used for evaporation preferably comprises 44-55 wt% of bismuth, 23-27 wt% of lead, 12-14 wt% of tin and 10-15 wt% of cadmium; the substrate temperature for vapor deposition is preferably 40-60 deg.C, specifically 40 deg.C, 41 deg.C, 42 deg.C, 43 deg.C, 44 deg.C, 45 deg.C, 46 deg.C, 47 deg.C, 48 deg.C, 49 deg.C, 50 deg.C, 51 deg.C, 52 deg.C, 53 deg.C, 54 deg.C55 deg.C, 56 deg.C, 57 deg.C, 58 deg.C, 59 deg.C or 60 deg.C; the evaporation temperature of the evaporation is preferably 170-400 ℃, and specifically can be 170 ℃, 175 ℃, 180 ℃, 185 ℃, 190 ℃, 195 ℃, 200 ℃, 210 ℃, 220 ℃, 230 ℃, 240 ℃, 250 ℃, 270 ℃, 300 ℃, 320 ℃, 350 ℃, 370 ℃ or 400 ℃; the evaporation speed of the evaporation is preferably 1-5 crystal oscillation points/second, and specifically can be 1 crystal oscillation point/second, 2 crystal oscillation points/second, 3 crystal oscillation points/second, 4 crystal oscillation points/second or 5 crystal oscillation points/second; the degree of vacuum of the vapor deposition is preferably 5X 10-4～3×10-4Pa, specifically 5X 10-4Pa、4.5×10-4Pa、4×10-4Pa、3.5×10-4Pa or 3X 10-4Pa; the evaporation power is preferably 3000-5000W, and specifically 3000W, 3500W, 4000W, 4500W or 5000W. After the wude alloy plating is finished, a wude alloy film layer is formed on the substrate, wherein the thickness of the wude alloy film layer is preferably 50-100 nm, and specifically can be 50nm, 55nm, 60nm, 65nm, 70nm, 75nm, 80nm, 85nm, 90nm, 95nm or 100 nm.
In the preparation method provided by the invention, after the Wude alloy film layer is formed, the magnesium alloy magnetic material is plated on the Wude alloy layer. Wherein, the plating mode is preferably magnetron sputtering; the sputtering rate of the magnetron sputtering is preferably 5-10 nm/s, and specifically can be 5nm/s, 5.5nm/s, 6nm/s, 6.5nm/s, 7nm/s, 7.5nm/s, 8nm/s, 8.5nm/s, 9nm/s, 9.5nm/s or 10 nm/s; the magnetron sputtering time is preferably 40-120 s, and specifically can be 40s, 45s, 50s, 55s, 60s, 65s, 70s, 75s, 80s, 85s, 90s, 95s, 100s, 105s, 110s, 115s or 120 s; the degree of vacuum of the magnetron sputtering is preferably 5X 10-4～3×10-4Pa, specifically 5X 10-4Pa、4.5×10-4Pa、4×10-4Pa、3.5×10-4Pa or 3X 10-4Pa; the temperature of the substrate for magnetron sputtering is preferably 80-100 ℃, and specifically can be 80 ℃, 85 ℃, 90 ℃, 95 ℃ or 100 ℃; the magnetron sputtering power is preferably 3000-5000W, and specifically can be 3000W, 3500W, 4000W, 4500W or 5000W. In the invention, the magnesium alloy target material used for magnetron sputtering is preferably prepared according to the following steps: i) putting magnesium ingot intoHeating in a crucible heating furnace, adding zinc ingots, titanium ingots, silicon ingots and iron in sequence after magnesium ingots are completely melted, and stirring to obtain magnesium alloy melt with uniform components; ii) casting the magnesium alloy melt into a cast rod crystallizer, and solidifying the magnesium alloy to form a magnesium alloy rod material; and iii) placing the magnesium alloy rod and the die into a heating furnace for heating, cooling and extruding to obtain the magnesium alloy target. In the step i), the heating temperature of the heating furnace is preferably 700-800 ℃, and specifically can be 700 ℃, 710 ℃, 720 ℃, 730 ℃, 740 ℃, 750 ℃, 760 ℃, 770 ℃, 780 ℃, 790 ℃ or 800 ℃; in the step ii), the temperature of the magnesium alloy melt before casting is preferably kept at 740-760 ℃, and specifically can be 740 ℃, 745 ℃, 750 ℃, 755 ℃ or 760 ℃; in step iii), the heating temperature is preferably 520-560 ℃, and specifically can be 520 ℃, 525 ℃, 530 ℃, 535 ℃, 540 ℃, 545 ℃, 550 ℃, 555 ℃ or 560 ℃; in step iii), the temperature of the temperature reduction is preferably 350-400 ℃, and specifically may be 350 ℃, 355 ℃, 360 ℃, 365 ℃, 370 ℃, 375 ℃, 380 ℃, 385 ℃, 390 ℃, 395 ℃ or 400 ℃.
In the preparation method provided by the invention, after the magnesium alloy magnetic material is plated, a magnesium alloy magnetic film layer is formed on the Wude alloy film layer. The magnesium alloy magnetic film layer preferably comprises magnesium, zinc, titanium, silicon and ferroferric oxide; the content of the magnesium is preferably 40-50 wt%, and specifically can be 40 wt%, 41 wt%, 42 wt%, 43 wt%, 44 wt%, 45 wt%, 46 wt%, 47 wt%, 48 wt%, 49 wt% or 50 wt%; the content of the zinc is preferably 10-20 wt%, and specifically can be 10 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt%, 15 wt%, 16 wt%, 17 wt%, 18 wt%, 19 wt% or 20 wt%; the content of the titanium is preferably 10-20 wt%, and specifically 10 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt%, 15 wt%, 16 wt%, 17 wt%, 18 wt%, 19 wt% or 20 wt%; the content of the silicon is preferably 10-20 wt%, and specifically can be 10 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt%, 15 wt%, 16 wt%, 17 wt%, 18 wt%, 19 wt% or 20 wt%; the content of the ferroferric oxide is preferably 5-15 wt%, and specifically can be 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt% or 15 wt%. In the invention, the thickness of the magnesium alloy magnetic film layer is preferably 10-1000 nm, and specifically may be 10nm, 20nm, 30nm, 40nm, 50nm, 70nm, 100nm, 150nm, 200nm, 250nm, 300nm, 400nm, 500nm, 600nm, 700nm, 800nm, 900nm or 1000 nm.
In the preparation method provided by the invention, after the magnesium alloy magnetic film layer is formed, a multilayer composite material is obtained, and then the multilayer composite material is heated until the Wude alloy film layer in the material is dissolved (the Wude alloy film layer is dissolved at about 71 ℃). Wherein the heating is preferably carried out in water; the heating temperature is preferably 75-80 ℃, and specifically can be 75 ℃, 76 ℃, 77 ℃, 78 ℃, 79 ℃ or 80 ℃. In one embodiment of the present invention, the heating of the multilayer composite material is preferably performed in a water tank, as shown in fig. 1, fig. 1 is a schematic diagram of the operation of heating and melting the wude alloy film layer provided in the embodiment of the present invention, wherein 1 denotes the water tank, 2 denotes the fixing member, 3 denotes the substrate, 4 denotes the wude alloy film layer, and 5 denotes the magnesium alloy magnetic film layer. In one embodiment of the present invention, the heating process includes: and placing the multilayer composite material in a water tank, heating the water tank to the heating temperature, and then preserving heat for a period of time. Wherein the initial temperature of the water tank is preferably 15-35 ℃, and specifically can be room temperature (25 ℃); the heating rate is preferably 1-10 ℃/min, more preferably 3-7 ℃/min, and specifically can be 3 ℃/min, 4 ℃/min, 5 ℃/min, 6 ℃/min or 7 ℃/min; the heat preservation time is preferably 3-15 min, more preferably 5-10 min, and specifically can be 5min, 6min, 7min, 8min, 9min or 10 min. After the Wude alloy film layer is dissolved, the magnesium alloy magnetic film layer is separated from the substrate.
In the preparation method provided by the invention, after the obtained magnesium alloy magnetic film layer is separated, cutting and shaping are carried out on the magnesium alloy magnetic film layer to obtain the magnesium alloy magnetic body meeting the size requirement (for example, the size of the magnesium alloy magnetic body for cardiovascular diagnosis and treatment is sub-millimeter magnitude, and the size of the magnesium alloy magnetic body for gastrointestinal tract and solid tumor diagnosis and treatment is millimeter to centimeter magnitude). Wherein, the cutting and shaping mode is preferably laser cutting; the scanning step of the laser cutting is preferably 10-200 nm/s, and specifically can be 10nm/s, 20nm/s, 30nm/s, 40nm/s, 50nm/s, 60nm/s, 70nm/s, 80nm/s, 90nm/s, 100nm/s, 110nm/s, 120nm/s, 130nm/s, 140nm/s, 150nm/s, 160nm/s, 170nm/s, 180nm/s, 190nm/s or 200 nm/s; the laser spot of the laser cutting is preferably 0.05-0.1 μm, and specifically can be 0.05 μm, 0.06 μm, 0.07 μm, 0.08 μm, 0.09 μm or 0.1 μm; the electron beam energy of the laser cutting is preferably 10-100 mJ, and specifically can be 10mJ, 20mJ, 30mJ, 40mJ, 50mJ, 60mJ, 70mJ, 80mJ, 90mJ or 100 mJ; the cutting precision of the laser cutting is preferably less than 100 nm. In the present invention, the shape of the cutting and shaping is not particularly limited, and includes, but is not limited to, a cylindrical shape, a cubic shape, or an irregular pattern. In an embodiment of the present invention, fig. 2 shows a magnesium alloy magnetic body obtained after cutting and shaping, and fig. 2 is a schematic structural view of the magnesium alloy magnetic body provided in the embodiment of the present invention, where a is a cylindrical cut, b is a cubic cut, c is a triangular prism cut, and d is a hexagonal prism cut.
In the preparation method provided by the invention, after the magnesium alloy magnetic body is obtained, the magnesium alloy magnetic body and the anti-inflammatory drug are mixed in the solvent. Wherein, before being mixed with the anti-inflammatory drug, the magnesium alloy magnetic body obtained after cutting and shaping is preferably dried and disinfected; the drying is preferably carried out in a vacuum environment below 50 Pa; the mode of disinfection is preferably ultraviolet-ozone disinfection. In the invention, the ultraviolet-ozone disinfection is carried out to remove the residual organic matters on the surface of the magnesium alloy magnetic body, promote the surface oxidation and increase the smoothness and the flatness of the surface and the inner side. In the present invention, the anti-inflammatory drug includes, but is not limited to, one or more of paclitaxel, rapamycin, arsenic trioxide, and everolimus; such solvents include, but are not limited to, acetone; the mass ratio of the magnesium alloy magnetic body to the anti-inflammatory drug is preferably 5: (5-20), specifically 5:5, 5:10, 5:15 or 5: 20. In the present invention, preferably, the anti-inflammatory drug is first ultrasonically mixed with the solvent to obtain an anti-inflammatory drug solution; and then mixing the anti-inflammatory drug solution with the magnesium alloy magnetic body.
In the preparation method provided by the invention, the magnesium alloy magnetic body and the anti-inflammatory drug are mixed in the solvent and then are subjected to centrifugal separation. Wherein the rotating speed of the centrifugal separation is preferably 8000-10000 r/min, and specifically 8000r/min, 8500r/min, 9000r/min, 9500r/min or 10000 r/min; the time of the centrifugal separation is preferably 60-180 min, and specifically can be 60min, 70min, 80min, 90min, 100min, 110min, 120min, 130min, 140min, 150min, 160min, 170min or 180 min. After the centrifugal separation, the supernatant was discarded, and the precipitate was dried. Wherein the drying mode is preferably vacuum drying; the drying temperature is preferably 60-100 ℃, and specifically can be 60 ℃, 65 ℃, 70 ℃, 75 ℃, 80 ℃, 85 ℃, 90 ℃, 95 ℃ or 100 ℃; the drying time is preferably 60-90 min, and specifically can be 60min, 65min, 70min, 75min, 80min, 85min or 90 min. And after drying, obtaining the magnesium alloy nano robot. The magnesium alloy nano robot comprises a magnesium alloy magnetic body and an anti-inflammatory drug compounded on the surface of the magnesium alloy magnetic body.
The preparation method provided by the invention selects the magnetic magnesium alloy as the main material of the nano robot, so that the nano robot can show good magnetism; meanwhile, the surface of the magnesium alloy magnetic body is loaded with anti-inflammatory drugs, so that inflammatory reaction induced by degradation of the nano robot can be greatly relieved; in addition, the preparation method can also realize the regulation and control of the degradation rate of the magnesium alloy nano robot by changing the composition and the size of the magnesium alloy magnetic body, thereby controlling the degradation time of the magnesium alloy nano robot.
The preparation method provided by the invention has stable and controllable production process and is suitable for industrialization. The experimental results show that: the magnesium alloy nano robot prepared by the method can basically complete degradation within 4-6 months, and cannot cause local inflammatory reaction in the degradation process.
The invention also provides a magnesium alloy nano robot prepared by the preparation method of the technical scheme. The magnesium alloy nano robot provided by the invention is prepared according to the method, has good size uniformity and magnetism, is controllable in degradation time, and does not cause local inflammatory reaction in the degradation process.
For the sake of clarity, the following examples are given in detail.
Example 1
The magnesium alloy nano robot is prepared according to the following specific process route: cleaning → evaporation coating of Wude alloy film → sputtering of magnesium alloy magnetic film → separation of magnetic film → cutting → drying and disinfection → drug loading.
1) Cleaning: the method comprises the steps of wiping a glass substrate with the size of 300mm multiplied by 400mm multiplied by 0.5mm with alcohol, then putting the glass substrate into an ultrasonic cleaning machine, carrying out ultra-washing with deionized water and alcohol, finally putting the glass substrate into alcohol steam for drying, and when the glass substrate is taken out of the steam, drying the glass substrate quickly because condensed steam is evaporated from the surface. In the present embodiment, the ultrasonic power in each ultrasonic process is 150W.
2) Evaporating a Wude alloy film layer: the method comprises the steps of utilizing a resistor to generate heat energy, placing a glass substrate base plate in a vacuum evaporation cavity, setting the evaporation temperature of evaporation Wude alloy target material to be 250 ℃, the evaporation base temperature to be 50 ℃, the evaporation speed to be 2 crystal oscillation points/second and the vacuum degree of the evaporation cavity to be 5 multiplied by 10, wherein the evaporation Wude alloy target material comprises 50 wt% of bismuth (Bi), 25 wt% of lead (Pb), 12.5 wt% of tin (Sn) and 12.5 wt% of cadmium (Cd)-4Pa, setting the power of the evaporation plating to 3000W, and the thickness of the plated Wude alloy film layer to 80 nm.
3) Sputtering a magnesium alloy magnetic film layer: plating a magnesium alloy film layer on the Wude alloy film layer by adopting a vacuum magnetron sputtering method; the sputtering rate is 7nm/s, the coating time is 80s, and the vacuum degree is 5 multiplied by 10-4Pa, 3000W of power, the substrate temperature at 90 ℃ and the thickness of the film layer at 100 nm.
3.1) the magnesium alloy target material used by the vacuum magnetron sputtering comprises the following components: mg 45 wt%, Zn 15 wt%, Ti 15 wt%, Si 15 wt%, Fe3O4 10wt％；
3.2) preparing the magnesium alloy target: firstly, putting a magnesium ingot into a crucible heating furnace, heating furnace charge to 750 ℃, after the magnesium ingot is completely melted, adding a zinc ingot, a titanium ingot, a silicon ingot and iron in sequence, and stirring to obtain a magnesium alloy melt with uniform components; keeping the temperature at 750 ℃ and preparing for casting; casting the magnesium alloy melt into a cast rod crystallizer, and solidifying the magnesium alloy to form a magnesium alloy rod material; finally, the magnesium alloy bar and the die are placed in a heating furnace to be heated to 540 ℃, and the temperature is reduced to 380 ℃ for extrusion, so as to obtain the magnesium alloy target.
4) Magnetic film separation: horizontally placing the multilayer composite material prepared in the step 3) in a flowing pure water fixing groove, heating the multilayer composite material to the temperature of 25 ℃, heating the multilayer composite material in a heating groove at the heating rate of 5 ℃/min to the temperature of 75 ℃, then preserving heat until the Wude alloy film layer in the multilayer composite material is completely dissolved (approximately preserving heat for 5-10 min), and separating the magnesium alloy magnetic film layer from the substrate after the Wude alloy film layer is completely dissolved.
5) Cutting the magnetic film layer: and (3) carrying out laser cutting on the magnesium alloy magnetic film layer obtained in the step (4), wherein the scanning step of the laser cutting is 1000nm/s, the laser spot is 0.05 mu m, the energy of an electron beam is 200mJ, and the cutting precision is less than 100nm, so that a cylindrical magnesium alloy magnetic body shown in a figure 2 is obtained, and the diameter of the magnesium alloy magnetic body is 200 nm.
6) Drying and sterilizing: putting the magnesium alloy magnetic body prepared in the step 5) into a vacuum environment with the pressure below 50Pa for drying treatment, and then carrying out ultraviolet-ozone surface disinfection treatment.
7) Carrying out medicine loading: adding 10mg of paclitaxel into 50mL of acetone, completely dissolving by ultrasonic treatment, placing the solution into a centrifuge tube, adding 5mg of the magnesium alloy magnetic body treated in the step 6), centrifuging the solution in an ultracentrifuge (Sigma company in Germany) at 9000r/min for 120min, discarding the supernatant, and placing the centrifuge tube into a vacuum drying oven to dry the solution at 80 ℃ to constant weight (about 70min) to obtain the magnesium alloy magnetic nano robot.
Example 2
The magnesium alloy nano robot is prepared according to the following specific process route: cleaning → evaporation coating of Wude alloy film → sputtering of magnesium alloy magnetic film → separation of magnetic film → cutting → drying and disinfection → drug loading.
1) Cleaning: the method comprises the steps of wiping a glass substrate with the size of 300mm multiplied by 400mm multiplied by 0.5mm with alcohol, then putting the glass substrate into an ultrasonic cleaning machine, carrying out ultra-washing with deionized water and alcohol, finally putting the glass substrate into alcohol steam for drying, and when the glass substrate is taken out of the steam, drying the glass substrate quickly because condensed steam is evaporated from the surface. In the present embodiment, the ultrasonic power in each ultrasonic process is 150W.
2) Evaporating a Wude alloy film layer: the method comprises the steps of utilizing a resistor to generate heat energy, placing a glass substrate base plate in a vacuum evaporation cavity, setting the evaporation temperature of evaporation Wude alloy target material to be 250 ℃, the evaporation base temperature to be 50 ℃, the evaporation speed to be 2 crystal oscillation points/second and the vacuum degree of the evaporation cavity to be 5 multiplied by 10, wherein the evaporation Wude alloy target material comprises 50 wt% of bismuth (Bi), 25 wt% of lead (Pb), 12.5 wt% of tin (Sn) and 12.5 wt% of cadmium (Cd)-4Pa, setting the power of the evaporation plating to 3000W, and the thickness of the plated Wude alloy film layer to 80 nm.
3) Sputtering a magnesium alloy magnetic film layer: plating a magnesium alloy film layer on the Wude alloy film layer by adopting a vacuum magnetron sputtering method; the sputtering rate is 7nm/s, the coating time is 80s, and the vacuum degree is 5 multiplied by 10-4Pa, 3000W of power, the substrate temperature at 90 ℃ and the thickness of the film layer at 100 nm.
3.1) the magnesium alloy target material used by the vacuum magnetron sputtering comprises the following components: mg 40 wt%, Zn 15 wt%, Ti 15 wt%, Si 15 wt%, Fe3O4 15wt％；
3.2) preparing the magnesium alloy target: firstly, putting a magnesium ingot into a crucible heating furnace, heating furnace materials to 700 ℃, after the magnesium ingot is completely melted, sequentially adding a zinc ingot, a titanium ingot, a silicon ingot and iron, and stirring to obtain a magnesium alloy melt with uniform components; keeping the temperature at 700 ℃ and preparing for casting; casting the magnesium alloy melt into a cast rod crystallizer, and solidifying the magnesium alloy to form a magnesium alloy rod material; finally, the magnesium alloy bar and the die are placed into a heating furnace to be heated to 520 ℃, cooled to 350 ℃ and extruded to obtain the magnesium alloy target.
4) Magnetic film separation: horizontally placing the multilayer composite material prepared in the step 3) in a flowing pure water fixing groove, heating the multilayer composite material to the temperature of 25 ℃, heating the multilayer composite material in a heating groove at the heating rate of 5 ℃/min to the temperature of 75 ℃, then preserving heat until the Wude alloy film layer in the multilayer composite material is completely dissolved (approximately preserving heat for 5-10 min), and separating the magnesium alloy magnetic film layer from the substrate after the Wude alloy film layer is completely dissolved.
5) Cutting the magnetic film layer: and (3) carrying out laser cutting on the magnesium alloy magnetic film layer obtained in the step (4), wherein the scanning step of the laser cutting is 1000nm/s, the laser spot is 0.05 mu m, the energy of an electron beam is 200mJ, and the cutting precision is less than 100nm, so that a cylindrical magnesium alloy magnetic body shown in a figure 2 is obtained, and the diameter of the magnesium alloy magnetic body is 200 nm.
6) Drying and sterilizing: putting the magnesium alloy magnetic body prepared in the step 5) into a vacuum environment with the pressure below 50Pa for drying treatment, and then carrying out ultraviolet-ozone surface disinfection treatment.
7) Carrying out medicine loading: adding 10mg of paclitaxel into 50mL of acetone, completely dissolving by ultrasonic treatment, placing the solution into a centrifuge tube, adding 5mg of the magnesium alloy magnetic body treated in the step 6), centrifuging the solution in an ultracentrifuge (Sigma company in Germany) at 9000r/min for 120min, discarding the supernatant, and placing the centrifuge tube into a vacuum drying oven to dry the solution at 80 ℃ to constant weight (about 70min) to obtain the magnesium alloy magnetic nano robot.
Example 3
The magnesium alloy nano robot is prepared according to the following specific process route: cleaning → evaporation coating of Wude alloy film → sputtering of magnesium alloy magnetic film → separation of magnetic film → cutting → drying and disinfection → drug loading.
1) Cleaning: the method comprises the steps of wiping a glass substrate with the size of 300mm multiplied by 400mm multiplied by 0.5mm with alcohol, then putting the glass substrate into an ultrasonic cleaning machine, carrying out ultra-washing with deionized water and alcohol, finally putting the glass substrate into alcohol steam for drying, and when the glass substrate is taken out of the steam, drying the glass substrate quickly because condensed steam is evaporated from the surface. In the present embodiment, the ultrasonic power in each ultrasonic process is 150W.
2) Evaporating a Wude alloy film layer: the method comprises the steps of utilizing a resistor to generate heat energy, placing a glass substrate base plate in a vacuum evaporation cavity, setting the evaporation temperature of evaporation Wude alloy target material to be 250 ℃, the evaporation base temperature to be 50 ℃, the evaporation speed to be 2 crystal oscillation points/second and the vacuum degree of the evaporation cavity to be 5 multiplied by 10, wherein the evaporation Wude alloy target material comprises 50 wt% of bismuth (Bi), 25 wt% of lead (Pb), 12.5 wt% of tin (Sn) and 12.5 wt% of cadmium (Cd)-4Pa，The power of the deposition is set to 3000W, and the thickness of the plated Wude alloy film layer is 80 nm.
3) Sputtering a magnesium alloy magnetic film layer: plating a magnesium alloy film layer on the Wude alloy film layer by adopting a vacuum magnetron sputtering method; the sputtering rate is 7nm/s, the coating time is 80s, and the vacuum degree is 5 multiplied by 10-4Pa, 3000W of power, the substrate temperature at 90 ℃ and the thickness of the film layer at 100 nm.
3.1) the magnesium alloy target material used by the vacuum magnetron sputtering comprises the following components: mg 50 wt%, Zn 15 wt%, Ti 15 wt%, Si 15 wt%, Fe3O4 5wt％；
3.2) preparing the magnesium alloy target: firstly, putting a magnesium ingot into a crucible heating furnace, heating furnace charge to 800 ℃, after the magnesium ingot is completely melted, adding a zinc ingot, a titanium ingot, a silicon ingot and iron in sequence, and stirring to obtain a magnesium alloy melt with uniform components; keeping the temperature at 800 ℃ and preparing for casting; casting the magnesium alloy melt into a cast rod crystallizer, and solidifying the magnesium alloy to form a magnesium alloy rod material; finally, the magnesium alloy bar and the die are placed in a heating furnace to be heated to 560 ℃, cooled to 400 ℃ and extruded to obtain the magnesium alloy target.
4) Magnetic film separation: horizontally placing the multilayer composite material prepared in the step 3) in a flowing pure water fixing groove, heating the multilayer composite material to the temperature of 25 ℃, heating the multilayer composite material in a heating groove at the heating rate of 5 ℃/min to the temperature of 75 ℃, then preserving heat until the Wude alloy film layer in the multilayer composite material is completely dissolved (approximately preserving heat for 5-10 min), and separating the magnesium alloy magnetic film layer from the substrate after the Wude alloy film layer is completely dissolved.
5) Cutting the magnetic film layer: and (3) carrying out laser cutting on the magnesium alloy magnetic film layer obtained in the step (4), wherein the scanning step of the laser cutting is 1000nm/s, the laser spot is 0.05 mu m, the energy of an electron beam is 200mJ, and the cutting precision is less than 100nm, so that a cylindrical magnesium alloy magnetic body shown in a figure 2 is obtained, and the diameter of the magnesium alloy magnetic body is 200 nm.
6) Drying and sterilizing: putting the magnesium alloy magnetic body prepared in the step 5) into a vacuum environment with the pressure below 50Pa for drying treatment, and then carrying out ultraviolet-ozone surface disinfection treatment.
7) Carrying out medicine loading: adding 10mg of paclitaxel into 50mL of acetone, completely dissolving by ultrasonic treatment, placing the solution into a centrifuge tube, adding 5mg of the magnesium alloy magnetic body treated in the step 6), centrifuging the solution in an ultracentrifuge (Sigma company in Germany) at 9000r/min for 120min, discarding the supernatant, and placing the centrifuge tube into a vacuum drying oven to dry the solution at 80 ℃ to constant weight (about 70min) to obtain the magnesium alloy magnetic nano robot.
Comparative example 1
The magnesium alloy nano robot is prepared according to the following specific process route: cleaning → evaporation coating of Wude alloy film → sputtering of ferroferric oxide film → separation of magnetic film → cutting → drying and disinfection → drug loading.
1) Cleaning: the method comprises the steps of wiping a glass substrate with the size of 300mm multiplied by 400mm multiplied by 0.5mm with alcohol, then putting the glass substrate into an ultrasonic cleaning machine, carrying out ultra-washing with deionized water and alcohol, finally putting the glass substrate into alcohol steam for drying, and when the glass substrate is taken out of the steam, drying the glass substrate quickly because condensed steam is evaporated from the surface. In the present embodiment, the ultrasonic power in each ultrasonic process is 150W.
2) Evaporating a Wude alloy film layer: the method comprises the steps of utilizing a resistor to generate heat energy, placing a glass substrate base plate in a vacuum evaporation cavity, setting the evaporation temperature of evaporation Wude alloy target material to be 250 ℃, the evaporation base temperature to be 50 ℃, the evaporation speed to be 2 crystal oscillation points/second and the vacuum degree of the evaporation cavity to be 5 multiplied by 10, wherein the evaporation Wude alloy target material comprises 50 wt% of bismuth (Bi), 25 wt% of lead (Pb), 12.5 wt% of tin (Sn) and 12.5 wt% of cadmium (Cd)-4Pa, setting the power of the evaporation plating to 3000W, and the thickness of the plated Wude alloy film layer to 80 nm.
3) Sputtering of a ferroferric oxide film layer: and plating a ferroferric oxide film layer on the Wude alloy film layer by adopting a vacuum magnetron sputtering method, wherein the thickness of the film layer is 100 nm.
4) Magnetic film separation: horizontally placing the multilayer composite material prepared in the step 3) in a flowing pure water fixing groove, heating the multilayer composite material to the temperature of 25 ℃ at the rate of 5 ℃/min in a heating groove, heating the multilayer composite material to the temperature of 75 ℃, then preserving heat until the Wude alloy film layer in the multilayer composite material is completely dissolved (approximately preserving heat for 5-10 min), and separating the ferroferric oxide film layer from the substrate after the Wude alloy film layer is completely dissolved.
5) Cutting the magnetic film layer: and (3) carrying out laser cutting on the ferroferric oxide film layer obtained in the step (4), wherein the scanning step of the laser cutting is 1000nm/s, the laser spot is 0.05 mu m, the energy of an electron beam is 200mJ, and the cutting precision is less than 100nm, so that cylindrical ferroferric oxide particles shown as a in the figure 2 are obtained, and the diameter of the ferroferric oxide particles is 200 nm.
6) Drying and sterilizing: putting the ferroferric oxide particles prepared in the step 5) into a vacuum environment below 50Pa for drying treatment, and then carrying out ultraviolet-ozone surface disinfection treatment.
7) Carrying out medicine loading: adding 10mg of paclitaxel into 50mL of acetone, completely dissolving by ultrasonic waves, placing the mixture into a centrifugal tube, adding 5mg of the ferroferric oxide particles treated in the step 6), centrifuging the mixture in an ultracentrifuge (Sigma company in Germany) at 9000r/min for 120min, removing supernatant, and placing the centrifugal tube into a vacuum drying oven to dry the mixture at 80 ℃ to constant weight (about 70min) to obtain the ferroferric oxide magnetic nano robot.
Comparative example 2
The magnesium alloy nano robot is prepared according to the following specific process route: cleaning → evaporating Wude alloy film → sputtering magnesium alloy magnetic film → separating magnetic film → cutting → drying and sterilizing.
1) Cleaning: the method comprises the steps of wiping a glass substrate with the size of 300mm multiplied by 400mm multiplied by 0.5mm with alcohol, then putting the glass substrate into an ultrasonic cleaning machine, carrying out ultra-washing with deionized water and alcohol, finally putting the glass substrate into alcohol steam for drying, and when the glass substrate is taken out of the steam, drying the glass substrate quickly because condensed steam is evaporated from the surface. In the present embodiment, the ultrasonic power in each ultrasonic process is 150W.
2) Evaporating a Wude alloy film layer: the method comprises the steps of utilizing a resistor to generate heat energy, placing a glass substrate base plate in a vacuum evaporation cavity, setting the evaporation temperature of evaporation Wude alloy target material to be 250 ℃, controlling the evaporation temperature of an evaporation substrate to be 50 ℃, controlling the evaporation speed of evaporation to be 2 crystal oscillation points/second, and evaporating the Wude alloy target material to be 250 ℃, wherein the evaporation Wude alloy target material comprises 50 wt% of bismuth (Bi), 25 wt% of lead (Pb), 12.5 wt% of tin (Sn) and 12.5 wt% of cadmium (Cd)The vacuum degree of the plating chamber is set to 5 x 10-4Pa, setting the power of the evaporation plating to 3000W, and the thickness of the plated Wude alloy film layer to 80 nm.
3) Sputtering a magnesium alloy magnetic film layer: plating a magnesium alloy film layer on the Wude alloy film layer by adopting a vacuum magnetron sputtering method; the sputtering rate is 7nm/s, the coating time is 80s, and the vacuum degree is 5 multiplied by 10-4Pa, 3000W of power, the substrate temperature at 90 ℃ and the thickness of the film layer at 100 nm.
3.1) the magnesium alloy target material used by the vacuum magnetron sputtering comprises the following components: mg 45 wt%, Zn 15 wt%, Ti 15 wt%, Si 15 wt%, Fe3O4 10wt％；
3.2) preparing the magnesium alloy target: firstly, putting a magnesium ingot into a crucible heating furnace, heating furnace materials to 700-800 ℃, after the magnesium ingot is completely melted, sequentially adding a zinc ingot, a titanium ingot, a silicon ingot and iron, and stirring to obtain a magnesium alloy melt with uniform components; keeping the temperature at 750 ℃ and preparing for casting; casting the magnesium alloy melt into a cast rod crystallizer, and solidifying the magnesium alloy to form a magnesium alloy rod material; finally, the magnesium alloy bar and the die are placed in a heating furnace to be heated to 540 ℃, and the temperature is reduced to 380 ℃ for extrusion, so as to obtain the magnesium alloy target.
4) Magnetic film separation: horizontally placing the multilayer composite material prepared in the step 3) in a flowing pure water fixing groove, heating the multilayer composite material to the temperature of 25 ℃, heating the multilayer composite material in a heating groove at the heating rate of 5 ℃/min to the temperature of 75 ℃, then preserving heat until the Wude alloy film layer in the multilayer composite material is completely dissolved (approximately preserving heat for 5-10 min), and separating the magnesium alloy magnetic film layer from the substrate after the Wude alloy film layer is completely dissolved.
5) Cutting the magnetic film layer: and (3) carrying out laser cutting on the magnesium alloy magnetic film layer obtained in the step (4), wherein the scanning step of the laser cutting is 1000nm/s, the laser spot is 0.05 mu m, the energy of an electron beam is 200mJ, and the cutting precision is less than 100nm, so that the cylindrical magnesium alloy magnetic nano robot shown as a in the figure 2 is obtained, and the diameter of the magnesium alloy magnetic nano robot is 200 nm.
6) Drying and sterilizing: putting the magnesium alloy magnetic nano robot prepared in the step 5) into a vacuum environment below 50Pa for drying treatment, and then performing ultraviolet-ozone surface disinfection treatment.
Performance testing
Diluting 1mg of nano robot into saline water, then injecting the saline water into a tumor area of a patient, and finally completely covering the tumor area with the magnesium alloy nano robot through an external magnetic control system; the range of the nano robot exceeds the tumor range by more than 5mm and is defined as complete coverage;
the tissue to be heated is placed between a pair of capacitance plates (the electrodes are not contacted with the human body), radio frequency voltage is applied between the electrodes (capacitance field method), when the thermotherapy is carried out, the tissue (nano robot) body between the capacitance plates absorbs electric field energy and converts the electric field energy into heat energy, thereby raising the temperature of the tissue. Generally, the radio frequency band is 13.56MHz, and the power is 0-800W.
And finally, recognizing the biocompatibility and degradation condition of the nano robot in vivo through CT images.
The heating principle is as follows: the nano magnetic fluid absorbs electromagnetic wave energy under the action of an alternating magnetic field to generate vibration motion, magnetic nano particles generate heat due to hysteresis loss, and tumor tissues accumulated by the heat transfer nano particles also generate heat. The tumor tissue has the advantages of distorted and expanded blood vessels, large blood resistance, unhealthy vascular receptors, poor temperature sensitivity, difficult heat dissipation under the action of high temperature, easy heat accumulation, quick temperature rise, huge heat storage reservoir formation and 5-10 ℃ temperature difference with normal tissue. If the temperature of the tumor tissue is brought to 43 ℃, the tumor cells are overheated and die.
The results of testing biocompatibility and degradation of the nano-robot are shown in table 1:
TABLE 1 biocompatibility and degradation of nanorobots of different examples and comparative examples
As can be seen from the table 1, the magnesium alloy nano robot prepared by the method can basically complete degradation within 4-6 months, and cannot cause local inflammatory reaction in the degradation process.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (10)
1. A preparation method of a magnesium alloy nano robot comprises the following steps:
a) plating a Wude alloy on the surface of the substrate to form a Wude alloy film layer;
b) plating a magnesium alloy magnetic material on the Wude alloy layer to form a magnesium alloy magnetic film layer;
c) heating the multilayer composite material obtained in the step b) until the Wude alloy film layer in the material is melted, and separating the magnesium alloy magnetic film layer from the substrate;
d) cutting and shaping the magnesium alloy magnetic film layer obtained by the separation in the step c) to obtain a magnesium alloy magnetic body;
e) and mixing the magnesium alloy magnetic body and the anti-inflammatory drug in a solvent, carrying out centrifugal separation, and discarding the supernatant to obtain the magnesium alloy nano robot.
2. The method according to claim 1, wherein in step b), the plating is performed by magnetron sputtering;
the sputtering rate of the magnetron sputtering is 5-10 nm/s; the magnetron sputtering time is 40-120 s; the vacuum degree of the magnetron sputtering is 5 multiplied by 10-4～3×10-4Pa; the substrate temperature of the magnetron sputtering is 80-100 ℃.
3. The preparation method according to claim 1, wherein in the step b), the components of the magnesium alloy magnetic film layer comprise magnesium, zinc, titanium, silicon and ferroferric oxide.
4. The preparation method according to claim 1, wherein in the step b), the thickness of the magnesium alloy magnetic film layer is 10-1000 nm.
5. The method of claim 1, wherein in step c), the multilayer composite is heated in water; the heating temperature is 75-80 ℃.
6. The method for preparing the composite material according to claim 1, wherein in the step d), the cutting shaping mode is laser cutting;
the scanning step of the laser cutting is 10-200 nm/s; the laser spot of the laser cutting is 0.05-0.1 mu m; the energy of the electron beam for laser cutting is 10-100 mJ.
7. The method of claim 1, wherein in step e), the anti-inflammatory drug comprises one or more of paclitaxel, rapamycin, arsenic trioxide, and everolimus.
8. The method according to claim 1, wherein in the step e), the mass ratio of the magnesium alloy magnetic body to the anti-inflammatory drug is 5: (5-20).
9. The method of claim 1, wherein the magnesium alloy magnetic body is dried and sterilized before being mixed with the anti-inflammatory agent in the step e).
10. The magnesium alloy nano robot prepared by the preparation method of any one of claims 1 to 9.
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