CN113663139A - Multi-spine nano-gold memory alloy stent with radiotherapy sensitization function and preparation method and application thereof - Google Patents
Multi-spine nano-gold memory alloy stent with radiotherapy sensitization function and preparation method and application thereof Download PDFInfo
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
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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
- A61L31/08—Materials for coatings
- A61L31/082—Inorganic materials
- A61L31/088—Other specific inorganic materials not covered by A61L31/084 or A61L31/086
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- 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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
- A61F2002/044—Oesophagi or esophagi or gullets
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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
- A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
- A61L2300/102—Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
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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
- A61L2300/606—Coatings
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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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
- A61N2005/1092—Details
- A61N2005/1098—Enhancing the effect of the particle by an injected agent or implanted device
Abstract
The invention provides a multi-spine nanogold memory alloy stent with a radiotherapy sensitization function, and a preparation method and application thereof, and relates to the technical field of medical instruments. The invention provides a multi-thorn nano-gold memory alloy bracket with a radiotherapy sensitization function, which comprises a bracket and a multi-thorn nano-gold layer covering the surface of the bracket; the multi-spine nano gold layer consists of a plurality of spine-shaped nano gold particles; the stent is a columnar latticed stent woven by nickel-titanium alloy wires. The multi-spine nano-gold memory alloy stent provided by the invention not only has the physical supporting treatment effect of a common stent, but also has the radiotherapy sensitization effect; the multi-spine nano-gold memory alloy stent can be used for repeated radiotherapy irradiation for multiple times, so that a stable radiotherapy sensitization effect is kept.
Description
Technical Field
The invention relates to the technical field of medical instruments, in particular to a multi-spine nano-gold memory alloy stent with a radiotherapy sensitization function, and a preparation method and application thereof.
Background
Surgery, radiotherapy and chemotherapy are three major clinical means for treating esophageal cancer, however, 60% of esophageal cancer patients are in the middle and advanced stage of cancer at the time of treatment, and basically lose the chance of surgical treatment, and the patients in the advanced stage often cannot bear systemic chemotherapy with high side effects due to weakness. With the development of the technology, radiotherapy which takes X-rays as a main means can gradually achieve higher penetration depth, higher three-dimensional treatment precision, stronger treatment effect and lower treatment side effect, and becomes one of the main treatment means of esophageal cancer. However, some patients with esophageal cancer are not sensitive to radiotherapy, and the tolerance of the radiotherapy is displayed, so that the treatment effect is low. In addition, the malignant stenosis caused by the invasive growth of the esophageal cancer can cause dysphagia of patients and further cause long-term nutrient intake disorder, and the patients are easy to have complications such as hypoproteinemia and electrolyte flocculation, and have extremely low life quality and poor treatment prognosis. Therefore, aiming at the patients who can not carry out operation chemotherapy and are insensitive to radiotherapy while solving the problem of esophageal stenosis of the patients, the improvement of the sensitivity of the radiotherapy is the basis for improving the basic symptoms of the patients, improving the life quality of the patients, prolonging the lives of the patients and maintaining the subsequent life.
Endoscopic stenting is the simplest and most effective palliative treatment currently addressing eating difficulties. However, the current self-expandable stent used clinically can only treat esophageal stenosis by relying on physical expansion, cannot treat tumors, and cannot fundamentally solve the problem of restenosis caused by tumor regrowth.
Disclosure of Invention
The invention aims to provide a multi-spine nanogold memory alloy stent with a radiotherapy sensitization function, and a preparation method and application thereof; the multi-spine nano-gold memory alloy stent can be used for repeated radiotherapy irradiation for multiple times, so that a stable radiotherapy sensitization effect is kept.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a multi-thorn nano-gold memory alloy bracket with a radiotherapy sensitization function, which comprises a bracket and a multi-thorn nano-gold layer covered on the surface of the bracket; the multi-spine nano gold layer consists of a plurality of spine-shaped nano gold particles; the stent is a columnar latticed stent woven by nickel-titanium alloy wires.
Preferably, the particle size of the spiky nano gold particles is 50-150 nm independently; the size of the spikes of the spiky-shaped gold nanoparticles is independently 30-50 nm.
Preferably, the thickness of the multi-spine nano gold layer is 0.5-3 μm.
Preferably, the diameter of the support is 16-20 mm, the length of the support is 50-120 mm, and the supporting force is 60-80 g/mm.
The invention provides a preparation method of the multi-spine nano-gold memory alloy stent in the technical scheme, which comprises the following steps:
mixing the stent and dopamine in a Tris buffer solution to obtain a polydopamine coating stent;
mixing the polydopamine coating stent and a chloroplatinic acid solution, and carrying out a thermal decomposition reaction to obtain a platinum coating stent;
and mixing the platinum coating stent with an ascorbic acid solution and a chloroauric acid solution, and carrying out in-situ reduction reaction to obtain the multi-spine nano-gold memory alloy stent.
Preferably, the concentration of the ascorbic acid solution is 80-200 mmol/L; the concentration of the chloroauric acid solution is 10-30 mg/mL.
Preferably, the temperature of the in-situ reduction reaction is room temperature; the time of the in-situ reduction reaction is 0.5-3 h.
Preferably, the temperature of the thermal decomposition reaction is 110-150 ℃; the time of the thermal decomposition reaction is 0.5-3 h.
The invention provides an application of the thorny nano-gold memory alloy stent in the technical scheme or the thorny nano-gold memory alloy stent prepared by the preparation method in the technical scheme in preparation of an anti-esophageal cancer product.
Preferably, the method of applying comprises: and irradiating the multi-spine nano-gold memory alloy stent by adopting X rays.
The invention provides a multi-thorn nano-gold memory alloy bracket with a radiotherapy sensitization function, which comprises a bracket and a multi-thorn nano-gold layer covered on the surface of the bracket; the multi-spine nano gold layer consists of a plurality of spine-shaped nano gold particles; the stent is a columnar latticed stent woven by nickel-titanium alloy wires. In the invention, the spiky-shaped gold nanoparticles are based on physicochemical properties, namely high atomic number (79) and high electron density (25 to 26 orders of magnitude per cubic meter), and the spikes which grow specifically in the morphology are used as electron distribution cores, so that the average action section and absorption coefficient of tissues and rays are effectively increased, and the transfer and deposition of physical dose of the rays in irradiated cells are improved. Meanwhile, under the irradiation of rays, the spiky-shaped gold nanoparticles are excited to generate secondary electrons which can initiate the free radical effect, so that the indirect damage of DNA is caused by attacking bases, ribose, oligonucleotide and the like, or the direct damage of biological membranes and proteins is caused by lipid peroxidation, thereby improving the radiotherapy effect and killing cancer cells. The multi-spine nanogold memory alloy stent provided by the invention has the double effects of physical support and radiotherapy sensitization, and the radiotherapy sensitization capability is stable, so that repeated ray irradiation does not damage the stent, and the stent can achieve the effect of long-term treatment.
In the invention, the radiotherapy sensitization refers to the cell ray sensitization generated after the spiky nano-gold particles on the surface of the multi-spiky nano-gold memory alloy stent are irradiated by radiotherapy rays and the generation of active oxygen species selectively kills tumor cells.
The multi-spine nanogold memory alloy stent provided by the invention has higher flexibility and is easy to reprocess and shape.
The invention also provides a preparation method of the multi-spine nano-gold memory alloy stent in the technical scheme. The invention adopts a unique in-situ multi-thorn nano-gold particle growth technology, and the nano-gold material is safe and nontoxic and has simple and rapid growth process. The method can ensure the stable existence of the spiky-shaped nano gold particles on the nickel-titanium alloy wire by growing the spiky-shaped nano gold particles in situ, has high oxidation resistance, corrosion resistance and stability, is not easy to fall off, can carry out repeated radiotherapy irradiation for many times, and keeps stable radiotherapy sensitization effect.
Different from the radiotherapy bracket and the drug eluting bracket which are clinically used at present, the bracket improves the radiotherapy precision and the treatment effect by utilizing the radiotherapy sensitization effect of the thorny nano-gold, and can efficiently treat partial radiotherapy insensitive tubular cancers. The multi-spine nanogold memory alloy stent prepared by the invention is safe, has good sensitization effect, simple preparation process, repeated use and convenient treatment process. The multi-spine nano-gold memory alloy stent prepared by the invention can be used for nickel-titanium alloy stents of all types and sizes, and has the advantages of high preparation speed and simple method.
Drawings
FIG. 1 is a scanning electron microscope image of a nickel-titanium alloy stent wire grown from untreated thorny nano-gold;
FIG. 2 is a scanning electron micrograph of a multi-thorn nanogold memory alloy stent wire prepared in example 1;
FIG. 3 is an enlarged scanning electron micrograph of the multi-thorn nanogold memory alloy stent prepared in example 1;
FIG. 4 is a partially enlarged view of the multi-thorn nano-Au memory alloy stent prepared in example 2;
FIG. 5 is an element scan of a SEM of a multi-spine nano-Au memory alloy stent prepared in example 3;
FIG. 6 is a scanning electron microscope image of a spherical nanogold film-coated stent prepared in comparative example 1;
FIG. 7 is a scanning electron micrograph of the multi-thorn nanogold memory alloy stent prepared in example 1 after multiple X-ray irradiations;
FIG. 8 is an electron spin resonance spectrum measured after the multi-spine nanogold memory alloy stent prepared in example 1 is placed in an aqueous solution and irradiated with X-rays for 5 minutes;
FIG. 9 is a graph showing the generation of reactive oxygen species in cells after incubation of cancer cells with the multi-thorn nanogold memory alloy stent prepared in example 1 for 8h, with and without irradiation of X-rays.
Detailed Description
The invention provides a multi-thorn nano-gold memory alloy bracket with a radiotherapy sensitization function, which comprises a bracket and a multi-thorn nano-gold layer covered on the surface of the bracket; the multi-spine nano gold layer consists of a plurality of spine-shaped nano gold particles; the stent is a columnar latticed stent woven by nickel-titanium alloy wires.
The multi-spine nano-gold memory alloy stent provided by the invention comprises a stent. In the invention, the stent is a columnar latticed stent woven by nickel-titanium alloy wires. The invention has no special requirements on the specific shape of the stent, and is suitable for various types of stents, such as esophageal stents, biliary stents, intestinal stents, urinary tract stents or tracheal stents.
In the invention, the diameter of the bracket is preferably 16-20 mm, the length is preferably 50-120 mm, and the supporting force is preferably 60-80 g/mm. The stent adopted by the invention is of a common specification (NT-SMA) approved for clinical use.
The multi-spine nano-gold memory alloy stent provided by the invention comprises a multi-spine nano-gold layer covering the surface of the stent. In the invention, the multi-spine nano gold layer consists of a plurality of spine-shaped nano gold particles. In the invention, the particle size of the spiky nano-gold particles is preferably 50-150 nm independently, and more preferably 80-100 nm; the size of the spikes of the spiky-shaped gold nanoparticles is preferably 30-50 nm independently.
In the invention, the thickness of the multi-spine nano gold layer is preferably 0.5-3 μm.
In the invention, a polydopamine coating is preferably further arranged between the stent and the multi-spine nano gold layer. The invention utilizes the polydopamine coating to improve the bonding strength of the multi-spine nano gold layer and the bracket.
The invention also provides a preparation method of the multi-spine nano-gold memory alloy stent in the technical scheme, which comprises the following steps:
mixing the stent and dopamine in a Tris buffer solution to obtain a polydopamine coating stent;
mixing the polydopamine coating stent and a chloroplatinic acid solution, and carrying out a thermal decomposition reaction to obtain a platinum coating stent;
and mixing the platinum coating stent with an ascorbic acid solution and a chloroauric acid solution, and carrying out in-situ reduction reaction to obtain the multi-spine nano-gold memory alloy stent.
In the present invention, unless otherwise specified, the starting materials for the preparation are all commercially available products well known to those skilled in the art.
The invention mixes the stent and dopamine in Tris buffer solution to obtain the polydopamine coating stent. In the present invention, the surface of the stent is preferably cleaned and then mixed with dopamine. The present invention does not require any particular method for cleaning the surface, and may be carried out by methods known to those skilled in the art.
In the present invention, the Tris Buffer preferably includes a Tris-HCl Buffer or a Tris-Buffer. In the invention, the pH value of the Tris buffer solution is preferably 6.5-11.0, and more preferably 8.5. In the invention, the concentration of the Tris buffer solution is preferably 1-15 mmol/L, and more preferably 8-10 mmol/L.
In the invention, the concentration of the dopamine in the Tris buffer solution is preferably 1-10 mg/mL, and more preferably 2-5 mg/mL.
In the present invention, the mixing of the scaffold and dopamine is preferably performed under light-shielding conditions; the mixing is preferably carried out under stirring conditions; the mixing time is preferably 8-15 h, and more preferably 12 h. In the mixing process, dopamine is polymerized on the surface of the stent to form a polydopamine coating.
According to the invention, preferably, after the mixing, the stent is taken out, and the stent is washed by deionized water for 3-5 times, so as to obtain the polydopamine coating stent. The polydopamine particles which are not adsorbed on the surface of the stent are completely removed by cleaning.
The polydopamine coating is deposited on the surface of the stent, so that the adsorption of the platinum coating is facilitated.
After the polydopamine coating stent is obtained, the polydopamine coating stent and chloroplatinic acid solution are mixed for thermal decomposition reaction to obtain the platinum coating stent. In the present invention, the polydopamine coated stent and the chloroplatinic acid solution are preferably mixed in a hydrophilic solvent. In the invention, the concentration of the chloroplatinic acid solution is preferably 10-15 mg/mL. In the present invention, the hydrophilic solvent is preferably ethylene glycol; the invention has no special requirement on the dosage of the hydrophilic solvent, and can be used on the surface of a polydopamine coated stent. In a specific embodiment of the invention, the volume of the ethylene glycol is 400-600 mL; the volume of the chloroplatinic acid solution is 1-5 mL, and more preferably 1.5-2 mL.
In the invention, the temperature of the thermal decomposition reaction is preferably 100-150 ℃, and more preferably 110 ℃; the time of the thermal decomposition reaction is preferably 0.5-3 h, and more preferably 1-2 h. In the thermal decomposition reaction process, chloroplatinic acid is thermally decomposed into platinum which is adsorbed on the surface of the polydopamine coating to form a platinum coating.
According to the invention, preferably, after the thermal decomposition reaction, the obtained stent is taken out, and the stent is washed by deionized water for 3-5 times to obtain the platinum coating stent.
After the platinum coating stent is obtained, the method mixes the platinum coating stent with ascorbic acid solution and chloroauric acid solution, and carries out in-situ reduction reaction to obtain the multi-spine nano-gold memory alloy stent. In the invention, the concentration of the ascorbic acid solution is preferably 80-200 mmol/L, and more preferably 100-150 mmol/L; the concentration of the chloroauric acid solution is preferably 10-30 mg/mL, and more preferably 20-25 mg/mL. In the invention, the ascorbic acid has higher biological safety and is an endogenous reducing agent for human bodies. According to the invention, a chloroauric acid solution with a higher concentration is adopted, and under the combined action of platinum and ascorbic acid, a large amount of nano-gold can be quickly reduced in a short time, so that nano-gold particles form a sharp point shape, and a multi-spine nano-gold layer is further obtained.
The platinum-coated stent is preferably immersed in an ascorbic acid solution and then the chloroauric acid solution is added under stirring. The dosage of the ascorbic acid solution is not specially required, and the surface of the platinum-coated stent can be omitted. In a specific embodiment of the invention, the volume of the ascorbic acid solution is 400 mL; the volume of the chloroauric acid solution is 1-5 mL, and more preferably 1.5-3 mL. In the present invention, the stirring speed is preferably 800 to 1200rpm, and more preferably 1000 to 1100 rpm.
In the present invention, the temperature of the in situ reduction reaction is preferably room temperature; the time of the in-situ reduction reaction is preferably 0.5-3 h, and more preferably 1-2 h. In the in-situ reduction reaction process, the coordination capacity of platinum and polydopamine is better, the adsorption is firmer, and the platinum and the polydopamine can perform a displacement reaction, so that the nano-gold obtained by displacement can be firmly adsorbed on the surface of a polydopamine coating, on the other hand, the platinum provides a nucleation site during the reduction reaction, and the ascorbic acid can rapidly reduce the chloroauric acid due to the limitation of local electrons to form the spine-shaped nano-gold particles.
According to the invention, preferably, after the in-situ reduction reaction, the obtained stent is washed by deionized water for 3-5 times, and the thorny nano-gold memory alloy stent is obtained after drying. In the present invention, the drying is preferably vacuum drying.
The invention also provides the application of the thorny nano-gold memory alloy stent in the technical scheme or the thorny nano-gold memory alloy stent prepared by the preparation method in the technical scheme in the preparation of anti-esophageal cancer products. In the present invention, the method of application preferably comprises: and irradiating the multi-spine nano-gold memory alloy stent by adopting X rays.
After the multi-spine nanogold memory alloy stent is irradiated by X rays, the spine nanogold particles with high atomic number and high tip electron density have higher radiotherapy sensitivity enhancing capability, can improve the transfer and deposition of physical dose of the X rays in irradiated cells, enhance the generation of ROS in the cells, improve the sensitivity of the cells to the rays, and kill cancer cells by oxidative stress, cell cycle retardation and DNA repair inhibition.
The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. 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
(1) Preparing a polydopamine coating stent: firstly, the surface of a nickel-titanium alloy stent is cleaned, and then the stent is immersed in 8mmol/L Tris-HCl buffer solution (pH 8.5); adding dopamine into the solution to make the final concentration of the dopamine be 2 mg/mL; quickly stirring for 8h in a dark place; and taking out the stent, and washing the polydopamine coating stent by using deionized water for three times.
(2) Preparing a platinum coating stent: immersing the polydopamine coated stent in 400mL of glycol, and adding 1.5mL of chloroplatinic acid solution of 10 mg/mL; then heating the solution to 110 ℃, and carrying out thermal decomposition reaction for 1 h; the stent was removed and the platinum coated stent was washed three times with deionized water.
(3) Preparing a multi-spine nano gold memory alloy stent: immersing the platinum coating stent in 400mL and 100mmol/L ascorbic acid solution, adding 1.5mL and 20mg/mL chloroauric acid solution at the stirring speed of 1000rpm, carrying out in-situ reduction reaction for 1h, washing the stent with deionized water for three times, and drying under a vacuum condition to obtain the multi-spine nano-gold memory alloy stent.
The multi-spine nano-gold memory alloy stent prepared in the embodiment consists of a nickel-titanium alloy stent and a multi-spine nano-gold layer covering the surface of the nickel-titanium alloy stent; the multi-spine nano gold layer consists of a plurality of spine-shaped nano gold particles; the average grain diameter of the spiky nano gold particles is 80 nm.
Example 2
(1) Preparing a polydopamine coating stent: firstly, the surface of a nickel-titanium alloy stent is cleaned, and then the stent is immersed in 10mmol/L Tris-HCl buffer solution (pH 8.5); adding dopamine into the solution to make the final concentration of the dopamine be 5 mg/mL; quickly stirring for 12h in dark; and taking out the stent, and washing the polydopamine coating stent by using deionized water for three times.
(2) Preparing a platinum coating stent: immersing the polydopamine coated stent in 400mL of glycol, and adding 2mL of chloroplatinic acid solution with the concentration of 15 mg/mL; then heating the solution to 110 ℃, and carrying out thermal decomposition reaction for 1 h; the stent was removed and the platinum coated stent was washed three times with deionized water.
(3) Preparing a multi-spine nano gold memory alloy stent: immersing the platinum coating stent in 400mL and 100mmol/L ascorbic acid solution, adding 1.5mL and 20mg/mL chloroauric acid solution at the stirring speed of 1000rpm, carrying out in-situ reduction reaction for 1h, washing the stent with deionized water for three times, and drying under a vacuum condition to obtain the multi-spine nano-gold memory alloy stent.
The multi-spine nano-gold memory alloy stent prepared in the embodiment consists of a nickel-titanium alloy stent and a multi-spine nano-gold layer covering the surface of the nickel-titanium alloy stent; the multi-spine nano gold layer consists of a plurality of spine-shaped nano gold particles; the average grain diameter of the spiky nano gold particles is 100 nm.
Example 3
(1) Preparing a polydopamine coating stent: firstly, the surface of a nickel-titanium alloy stent is cleaned, and then the stent is immersed in 15mmol/L Tris-HCl buffer solution (pH 8.5); adding dopamine into the solution to make the final concentration of the dopamine be 10 mg/mL; quickly stirring for 12h in dark; and taking out the stent, and washing the polydopamine coating stent for 5 times by using deionized water.
(2) Preparing a platinum coating stent: immersing the polydopamine coated stent in 600mL of glycol, and adding 5mL of chloroplatinic acid solution and 10mg/mL of chloroplatinic acid solution; then heating the solution to 110 ℃, and carrying out thermal decomposition reaction for 1 h; the stent was removed and the platinum coated stent was washed 5 times with deionized water.
(3) Preparing a multi-spine nano gold memory alloy stent: immersing the platinum coating stent in 400mL and 150mmol/L ascorbic acid solution, adding 3mL and 20mg/mL chloroauric acid solution at the stirring speed of 1000rpm, carrying out in-situ reduction reaction for 1h, washing the stent with deionized water for three times, and drying under a vacuum condition to obtain the multi-spine nano-gold memory alloy stent.
The multi-spine nano-gold memory alloy stent prepared in the embodiment consists of a nickel-titanium alloy stent and a multi-spine nano-gold layer covering the surface of the nickel-titanium alloy stent; the multi-spine nano gold layer consists of a plurality of spine-shaped nano gold particles; the average particle size of the spiky nano gold particles is 150 nm.
Comparative example 1
(1) Firstly, cleaning the surface of a nickel-titanium alloy stent, and then immersing the stent in 5mmol/L Tris-Buffer (pH 8.5); adding dopamine into the solution to make the final concentration of the dopamine be 1 mg/mL; quickly stirring for 8h in a dark place; and taking out the stent, and washing the polydopamine coating stent by using deionized water for 1 time to obtain the polydopamine coating stent.
(2) Immersing the polydopamine coating stent in 400mL and 50mmol/L ascorbic acid solution, adding 1mL and 20mg/mL chloroauric acid solution, quickly stirring, carrying out in-situ reduction reaction for 1h, then carrying out rinsing for three times with deionized water, and drying under a vacuum condition to obtain the stent coated with the spherical nano gold film. The nano gold film prepared in this comparative example is a planar gold film.
Test example 1
The scanning electron microscope image of the nitinol stent wire grown without treatment of the multi-thorn nano-gold is shown in fig. 1. The scanning electron micrograph of the multi-spine nanogold memory alloy stent wire prepared in example 1 is shown in fig. 2. As can be seen from a comparison of FIGS. 1-2. The multi-spine nano gold layer in the multi-spine nano gold memory alloy stent prepared by the invention is effectively coated on the surface of the nickel-titanium alloy stent.
An enlarged scanning electron micrograph of the multi-spine nanogold memory alloy scaffold prepared in example 1 is shown in fig. 3. As can be seen from FIG. 3, the spiky-shaped gold nanoparticles are uniformly distributed and have uniform size.
An enlarged view of a portion of the multi-spine nanogold memory alloy stent prepared in example 2 is shown in fig. 4, and it can be seen from fig. 4 that the nanogold particles are actually spiky.
An element scanning image of a scanning electron microscope of the multi-spine nanogold memory alloy stent prepared in example 3 is shown in fig. 5. In FIG. 5, N, Ni and Ti elements indicate that the stent selected before being coated is a nickel-titanium alloy stent which is clinically approved; the effectiveness of the method is verified by the Au element, which shows that the method can prepare the nano-gold particles by in-situ reduction growth.
The scanning electron microscope image of the spherical nanogold film-coated stent prepared in comparative example 1 is shown in fig. 6. As can be seen from FIG. 6, the coated nanogold spheres are extremely uneven, are mostly in an agglomerated shape, are extremely easy to fall off, and directly influence the subsequent application of the stent.
The scanning electron micrograph of the multi-spine nanogold memory alloy stent prepared in example 1 after multiple X-ray irradiations is shown in fig. 7. As can be seen from FIG. 7, the multi-thorn nano gold layer has stable properties, is effectively anchored on the surface of the stent, and can be undamaged by repeated X-ray irradiation, so that the stent can achieve the effect of long-term treatment.
The electron spin resonance spectrum of the multi-spine nanogold memory alloy stent prepared in example 1, which was placed in an aqueous solution and measured after 5 minutes of X-ray irradiation, is shown in fig. 8. The curve without X-ray irradiation shows that the stent has no function of generating active oxygen and is harmless to cells, and the spectrum of hydroxyl free radicals is obviously generated after X-ray irradiation, so that the thorny nano-gold memory alloy stent can be effectively used for ray sensitization and cancer cell killing.
The generation of reactive oxygen free radicals in cells after incubation of cancer cells with the multi-spine nanogold memory alloy stent prepared in example 1 for 8h with and without irradiation with X-rays is shown in fig. 9. As can be seen from FIG. 9, the green fluorescence in the cells indicates that the spiny gold nanoparticles can effectively promote cell ray sensitization and generate active oxygen free radicals, thereby having potential application value in killing tumor cells.
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 multi-spine nano-gold memory alloy stent with radiotherapy sensitization function comprises a stent and a multi-spine nano-gold layer covering the surface of the stent; the multi-spine nano gold layer consists of a plurality of spine-shaped nano gold particles; the stent is a columnar latticed stent woven by nickel-titanium alloy wires.
2. The multi-spine nanogold memory alloy stent according to claim 1, wherein the particle size of the spine nanogold particles is independently 50 to 150 nm; the size of the spikes of the spiky-shaped gold nanoparticles is independently 30-50 nm.
3. The multi-spine nanogold memory alloy stent according to claim 1 or 2, wherein the thickness of the multi-spine nanogold layer is 0.5 to 3 μm.
4. The multi-thorn nano-gold memory alloy stent as claimed in claim 1, wherein the stent has a diameter of 16 to 20mm, a length of 50 to 120mm, and a supporting force of 60 to 80 g/mm.
5. The preparation method of the multi-spine nano-gold memory alloy stent as claimed in any one of claims 1 to 4, comprising the following steps:
mixing the stent and dopamine in a Tris buffer solution to obtain a polydopamine coating stent;
mixing the polydopamine coating stent and a chloroplatinic acid solution, and carrying out a thermal decomposition reaction to obtain a platinum coating stent;
and mixing the platinum coating stent with an ascorbic acid solution and a chloroauric acid solution, and carrying out in-situ reduction reaction to obtain the multi-spine nano-gold memory alloy stent.
6. The method according to claim 5, wherein the concentration of the ascorbic acid solution is 80 to 200 mmol/L; the concentration of the chloroauric acid solution is 10-30 mg/mL.
7. The production method according to claim 5 or 6, wherein the temperature of the in-situ reduction reaction is room temperature; the time of the in-situ reduction reaction is 0.5-3 h.
8. The method according to claim 5, wherein the temperature of the thermal decomposition reaction is 110 to 150 ℃; the time of the thermal decomposition reaction is 0.5-3 h.
9. Use of the thorny nano-gold memory alloy stent of any one of claims 1 to 4 or the thorny nano-gold memory alloy stent prepared by the preparation method of any one of claims 5 to 8 in preparation of an anti-esophageal cancer product.
10. The application according to claim 9, wherein the method of applying comprises: and irradiating the multi-spine nano-gold memory alloy stent by adopting X rays.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105030393A (en) * | 2015-07-24 | 2015-11-11 | 汇澜生物工程（浙江）有限公司 | Nanogold film memory alloy esophageal stent and preparing method thereof |
| CN106041119A (en) * | 2016-06-17 | 2016-10-26 | 西安交通大学 | Preparation method of thorn-shaped or petal-shaped rough-surface gold-silver alloy nanometer material |
| CN109609935A (en) * | 2019-01-11 | 2019-04-12 | 东南大学 | A method of preparing high density single dispersion metal nano particle on the surface of the material |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105030393A (en) * | 2015-07-24 | 2015-11-11 | 汇澜生物工程（浙江）有限公司 | Nanogold film memory alloy esophageal stent and preparing method thereof |
| CN106041119A (en) * | 2016-06-17 | 2016-10-26 | 西安交通大学 | Preparation method of thorn-shaped or petal-shaped rough-surface gold-silver alloy nanometer material |
| CN109609935A (en) * | 2019-01-11 | 2019-04-12 | 东南大学 | A method of preparing high density single dispersion metal nano particle on the surface of the material |
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Application publication date: 20211119 |