CN116652193A - Water-soluble tantalum nanoparticle and preparation method and application thereof - Google Patents
Water-soluble tantalum nanoparticle and preparation method and application thereof Download PDFInfo
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- CN116652193A CN116652193A CN202310367255.0A CN202310367255A CN116652193A CN 116652193 A CN116652193 A CN 116652193A CN 202310367255 A CN202310367255 A CN 202310367255A CN 116652193 A CN116652193 A CN 116652193A
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- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 title claims abstract description 209
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 162
- 229910052715 tantalum Inorganic materials 0.000 title claims abstract description 159
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 238000000498 ball milling Methods 0.000 claims abstract description 82
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 55
- 125000005341 metaphosphate group Chemical group 0.000 claims abstract description 40
- 239000000203 mixture Substances 0.000 claims abstract description 35
- 238000000034 method Methods 0.000 claims abstract description 32
- 238000002156 mixing Methods 0.000 claims abstract description 8
- 238000009210 therapy by ultrasound Methods 0.000 claims abstract description 8
- 238000004140 cleaning Methods 0.000 claims abstract description 6
- 239000000463 material Substances 0.000 claims description 41
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 10
- 239000004626 polylactic acid Substances 0.000 claims description 10
- GCLGEJMYGQKIIW-UHFFFAOYSA-H sodium hexametaphosphate Chemical compound [Na]OP1(=O)OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])O1 GCLGEJMYGQKIIW-UHFFFAOYSA-H 0.000 claims description 10
- 235000019982 sodium hexametaphosphate Nutrition 0.000 claims description 10
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 claims description 10
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 8
- 238000005119 centrifugation Methods 0.000 claims description 7
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 5
- 229940057838 polyethylene glycol 4000 Drugs 0.000 claims description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 5
- UGTZMIPZNRIWHX-UHFFFAOYSA-K sodium trimetaphosphate Chemical compound [Na+].[Na+].[Na+].[O-]P1(=O)OP([O-])(=O)OP([O-])(=O)O1 UGTZMIPZNRIWHX-UHFFFAOYSA-K 0.000 claims description 5
- UDEJEOLNSNYQSX-UHFFFAOYSA-J tetrasodium;2,4,6,8-tetraoxido-1,3,5,7,2$l^{5},4$l^{5},6$l^{5},8$l^{5}-tetraoxatetraphosphocane 2,4,6,8-tetraoxide Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P1(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])(=O)O1 UDEJEOLNSNYQSX-UHFFFAOYSA-J 0.000 claims description 5
- 229920001661 Chitosan Polymers 0.000 claims description 4
- 150000003904 phospholipids Chemical class 0.000 claims description 4
- 229960003237 betaine Drugs 0.000 claims description 3
- 229930182478 glucoside Natural products 0.000 claims description 3
- 150000008131 glucosides Chemical class 0.000 claims description 3
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 3
- 229920000136 polysorbate Polymers 0.000 claims description 3
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000002534 radiation-sensitizing agent Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 abstract description 31
- 239000007864 aqueous solution Substances 0.000 abstract description 8
- 230000000694 effects Effects 0.000 description 11
- 239000010410 layer Substances 0.000 description 11
- 239000002245 particle Substances 0.000 description 10
- 239000011248 coating agent Substances 0.000 description 9
- 238000000576 coating method Methods 0.000 description 9
- 238000001959 radiotherapy Methods 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- 230000008901 benefit Effects 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- BPUBBGLMJRNUCC-UHFFFAOYSA-N oxygen(2-);tantalum(5+) Chemical compound [O-2].[O-2].[O-2].[O-2].[O-2].[Ta+5].[Ta+5] BPUBBGLMJRNUCC-UHFFFAOYSA-N 0.000 description 7
- 229910001936 tantalum oxide Inorganic materials 0.000 description 7
- 238000001228 spectrum Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 5
- 238000003917 TEM image Methods 0.000 description 5
- 239000007853 buffer solution Substances 0.000 description 5
- 239000000084 colloidal system Substances 0.000 description 5
- 238000001027 hydrothermal synthesis Methods 0.000 description 5
- 238000003384 imaging method Methods 0.000 description 5
- 239000006087 Silane Coupling Agent Substances 0.000 description 4
- 229920002385 Sodium hyaluronate Polymers 0.000 description 4
- 238000005054 agglomeration Methods 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 238000000713 high-energy ball milling Methods 0.000 description 4
- 238000000464 low-speed centrifugation Methods 0.000 description 4
- 238000000593 microemulsion method Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 229940010747 sodium hyaluronate Drugs 0.000 description 4
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 4
- 238000001238 wet grinding Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 206010070834 Sensitisation Diseases 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
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- 230000002829 reductive effect Effects 0.000 description 3
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- 230000008313 sensitization Effects 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 238000001132 ultrasonic dispersion Methods 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
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- 239000000872 buffer Substances 0.000 description 2
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- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 239000002344 surface layer Substances 0.000 description 2
- 229910021524 transition metal nanoparticle Inorganic materials 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 229920001007 Nylon 4 Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
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- 238000011161 development Methods 0.000 description 1
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- 230000003670 easy-to-clean Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
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- 230000036541 health Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
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- 230000031700 light absorption Effects 0.000 description 1
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- 239000004530 micro-emulsion Substances 0.000 description 1
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- 229920001223 polyethylene glycol Polymers 0.000 description 1
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- 238000007669 thermal treatment Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0038—Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B22—CASTING; POWDER METALLURGY
- B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
- B22F1/00—Metallic powder; Treatment of metallic powder, e.g. to facilitate working or to improve properties
- B22F1/05—Metallic powder characterised by the size or surface area of the particles
- B22F1/054—Nanosized particles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B22—CASTING; POWDER METALLURGY
- B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
- B22F9/00—Making metallic powder or suspensions thereof
- B22F9/02—Making metallic powder or suspensions thereof using physical processes
- B22F9/04—Making metallic powder or suspensions thereof using physical processes starting from solid material, e.g. by crushing, grinding or milling
-
- 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
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B22—CASTING; POWDER METALLURGY
- B22F—WORKING METALLIC POWDER; MANUFACTURE OF ARTICLES FROM METALLIC POWDER; MAKING METALLIC POWDER; APPARATUS OR DEVICES SPECIALLY ADAPTED FOR METALLIC POWDER
- B22F9/00—Making metallic powder or suspensions thereof
- B22F9/02—Making metallic powder or suspensions thereof using physical processes
- B22F9/04—Making metallic powder or suspensions thereof using physical processes starting from solid material, e.g. by crushing, grinding or milling
- B22F2009/043—Making metallic powder or suspensions thereof using physical processes starting from solid material, e.g. by crushing, grinding or milling by ball milling
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention relates to a water-soluble tantalum nanoparticle and a preparation method and application thereof, belongs to the technical field of tantalum nanoparticles, and solves the problem that the tantalum nanoparticle prepared by the existing method has poor stability in high-concentration solution, and the preparation method of the water-soluble tantalum nanoparticle comprises the following steps: dissolving tantalum powder in water, performing ultrasonic treatment, and centrifuging to obtain refined tantalum powder; mixing the refined tantalum powder with metaphosphate to obtain a first mixture; subjecting the first mixture to first stage ballsGrinding to obtain a first mixture of ball milling in a first stage; adding proper amount of water into the first mixture after ball milling treatment, and adding proper amount of NaH 2 PO 4 And performing second-stage ball milling treatment on the solution, centrifuging and cleaning to obtain the water-soluble tantalum nano particles. The water-soluble tantalum nano particles prepared by the method have spherical shape, good water solubility and stable time in 60mg/mL aqueous solution for at least 48 hours.
Description
Technical Field
The invention relates to the technical field of tantalum nano materials, in particular to a water-soluble tantalum nano particle and a preparation method and application thereof.
Background
Cancer is the first killer of human health, many people lose life due to cancer every year, and the current cancer treatment mode mainly comprises radiotherapy and chemotherapy, because the hypoxic environment of tumor cells can lead to a great discount on the effect of radiotherapy, so a nanomaterial capable of enriching X-rays is needed to sensitize the effect of radiotherapy. Meanwhile, in order to accurately treat the tumor part, the tumor needs to be positioned by means of various imaging means. Computed tomography is a minimally invasive, safe, reliable imaging technique that can quickly and accurately reflect the state of a patient, and which typically requires contrast agents to enhance imaging. Iodine formulations are currently the most commonly used contrast agents, but due to their high osmotic pressure and viscosity, often cause adverse reactions, and further due to their short circulation time in the body, their ability to image for long periods of time is limited. Along with the development of nano technology, the transition metal nano particles can be designed in size, shape and function, and due to the nano size effect, the nano can prolong the internal circulation time, thereby providing a solution way for solving the problems of short internal circulation time and poor imaging effect of the iodine preparation, and meanwhile, the transition metal nano material also has high X-ray attenuation coefficient and can play a role in radiotherapy sensitization.
The transition metal nanoparticle tantalum has good biocompatibility and high radiation attenuation coefficient, and can provide better imaging effect while improving the radiotherapy sensitization effect. However, the existing water-soluble tantalum nano particles are mainly prepared by a microemulsion method and a hydrothermal method, the preparation method is complex and long in time, and toxic reagents are introduced in the preparation process. In addition, tantalum nanoparticles synthesized by the microemulsion method and the hydrothermal method cannot maintain stability for a long time at a high molar concentration, and the prepared morphology is mostly irregular.
The application field of the inorganic metal tantalum nano particles can be greatly improved by carrying out water-soluble treatment on the inorganic metal tantalum nano particles, and a plurality of methods for carrying out surface modification on the tantalum nano particles are available, and currently, the common methods are a hydrothermal synthesis method, a microemulsion method and a mechanochemical method. The surface active agents used for modifying the tantalum nano particles mainly comprise two types, namely silane coupling agents, the surface modification method through the silane coupling agents is carried out in a micro-emulsion environment or a hydrothermal environment, the synthesis process of a hydrothermal method and the micro-emulsion method is complex, the product contains partial toxic agents and is not easy to clean, and the water-soluble tantalum nano particles synthesized by the hydrothermal synthesis method also need to be subjected to additional surface treatment, so that the time consumption is long. Meanwhile, the silane coupling agent is not listed in the list of medical auxiliary materials, which also limits the biological application of the tantalum nano particles modified by the silane coupling agent. The other type is modified by a single medical adhesive, such as polypyrrolidone, polyethylene glycol, chitosan, polylactic acid, hydrophilic phospholipid and the like, and the tantalum nano particles modified by the method do not have high solution concentration stability and cannot be kept stable for a long time.
Disclosure of Invention
In view of the above analysis, the present invention provides a water-soluble tantalum nanoparticle, and a preparation method and application thereof, so as to solve the problem that the water-soluble tantalum nanoparticle prepared by the existing method has poor stability in a high-concentration solution.
In one aspect, the invention provides a method for preparing water-soluble tantalum nanoparticles, comprising the steps of:
(1) Dissolving tantalum powder in water, performing ultrasonic treatment, and centrifuging to obtain refined tantalum powder;
(2) Mixing the refined tantalum powder with metaphosphate to obtain a first mixture;
(3) Performing first-stage ball milling on the first mixture to obtain a first mixture subjected to first-stage ball milling;
(4) Adding a proper amount of water into the first mixture subjected to the first-stage ball milling treatment in the step (3), and then adding NaH 2 PO 4 And (3) performing ball milling treatment at the second stage until the pH value of the solution is 5.5-6.5, centrifuging and cleaning to obtain the water-soluble tantalum nano particles.
Further, the metaphosphate in the step (2) is one or more of sodium trimetaphosphate, sodium tetrametaphosphate and sodium hexametaphosphate.
Further, the mass ratio of the metaphosphate to the refined tantalum powder in the step (2) is 0.1-1.2.
Further, the ball milling rotating speed in the ball milling treatment of the first stage in the step (3) is 100-600r/min, and the ball milling time is 1-3h.
Furthermore, medical auxiliary materials are added into the water in the step (4).
Further, the medical auxiliary material is one or more of polyvinylpyrrolidone, polyethylene glycol 4000, polyethylene glycol 6000, betaine, glucoside, polylactic acid, chitosan, phospholipids or tween.
Further, the concentration of the medical auxiliary material in water is 0.5-1g/mL, and the mass ratio of the medical auxiliary material to the refined tantalum powder is 0.5-1.2.
Further, the ball milling rotating speed in the second stage ball milling treatment in the step (4) is 100-600r/min, and the ball milling time is 2-6h;
the centrifugation specifically comprises: centrifuging at 2000-3000r/min for 4-6min, and centrifuging at 10000-11000r/min for 10-15min.
In a second aspect, the invention provides a water-soluble tantalum nanoparticle prepared by the method, wherein the water-soluble tantalum nanoparticle is spherical and has a diameter of 30-60nm.
Further, the water-soluble tantalum nano particles are coated with a layer of hydrophilic film, and the thickness of the hydrophilic film is 4-6nm.
In a third aspect, the invention provides an application of the water-soluble tantalum nanoparticle in preparing a radiotherapy sensitizer.
Compared with the prior art, the invention has at least one of the following beneficial effects:
(1) According to the preparation method, metaphosphate is added into the water-soluble tantalum nano particles, and under the combined action of metaphosphate and high-energy ball milling in the first ball milling stage, the covalent bond of tantalum oxide on the surface of tantalum powder is broken to form tantalate, so that the surface charge of the tantalate is improved, and the solubility of the tantalate is improved; adding a proper amount of water in the second ball milling stage for wet milling treatment, so that the crushing efficiency of ball milling on large-particle tantalum is improved, meanwhile, metaphosphate can form a colloid state after absorbing water and is coated on the surface of tantalum nano particles, the stability of the tantalum nano particles in a high-water solution is improved, and the stability time in the water solution with the concentration of 60mg/mL is at least 48 hours;
(2) The method of the invention makes the prepared water-soluble tantalum nano particles present a monodisperse state, the tantalum nano particles are dispersed into tantalum nano particles with small particles by ball milling treatment, medical auxiliary materials are added to coat the tantalum nano particles, the medical auxiliary materials are in a macromolecular chain shape, and the chain-shaped macromolecules are vigorously mixed in the ball milling process to form a crossed and staggered reticular structure, so that the reticular structure has two advantages, firstly, more medical auxiliary materials can be coated on the surface of the tantalum nano particles, the biocompatibility is improved, secondly, metaphosphate loading can be carried out by using the reticular structure, and the solution stability is improved;
(3) By adding a proper amount of NaH 2 PO 4 The pH value of the reaction mixture is regulated to 5.5-6.5 by the solution, and the acidic inorganic salt solution can inhibit the hydrolysis of metaphosphate, improve the utilization rate of metaphosphate and increase the electric charge on the surface of the water-soluble tantalum nano particles;
(4) According to the method, through two-stage ball milling treatment, the mixture of tantalum nano particles and metaphosphate in a cross existing mode is promoted by the first-stage ball milling treatment, meanwhile, the surface of the material is activated by the high-energy ball milling treatment mode, the reaction of phosphate groups and the tantalum oxide film on the surface of the tantalum nano particles is promoted, covalent bonds of the tantalum oxide film on the surface of the water-soluble tantalum nano particles are broken to form tantalate, the surface charge of the tantalate is improved, and the solubility of the tantalate is improved; adding a proper amount of NaH 2 PO 4 The solution is subjected to second-stage ball milling treatment, wet milling treatment is adopted in the second stage, the crushing efficiency of ball milling on large-particle tantalum is improved, meanwhile, metaphosphate can form a colloid state after absorbing water and presents a long-chain state, the long chain is coated on the surface layer of tantalum nano particles to form a hydrophilic film, the hydrophilic film is negatively charged, and the agglomeration phenomenon is reduced through the repulsive action of electrostatic force, so that the solution is improvedStability of high water-solubility tantalum nanoparticles;
(5) The medical auxiliary materials are added into the preparation method, so that the synthesized water-soluble tantalum nano particles can keep good dispersibility and stability in organisms, the medical auxiliary materials and metaphosphate are coated on the surfaces of the tantalum nano particles, and the medical auxiliary materials exist in a mixed coating mode instead of a layer-by-layer coating mode, and the coating mode has the advantages of various surfactants, improves the surface charge repulsive force, has good biocompatibility and can keep better stability in human body environment;
(6) The water-soluble tantalum nano particles prepared by the invention can be coated with a hydrophilic film with the thickness of 4-6nm, the hydrophilic film is a mixed complex of metaphosphate and medical auxiliary materials or a metaphosphate single complex, the complex can improve the biostability of the water-soluble tantalum nano particles, and meanwhile, more metaphosphate long chains can be coupled, so that the surface charge of the water-soluble tantalum nano particles is improved.
In the invention, the technical schemes can be mutually combined to realize more preferable combination schemes. Additional features and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objectives and other advantages of the invention may be realized and attained by the structure particularly pointed out in the written description and drawings.
Drawings
The drawings are only for purposes of illustrating particular embodiments and are not to be construed as limiting the invention, like reference numerals being used to refer to like parts throughout the several views.
FIG. 1 is a TEM image of water-soluble tantalum nanoparticles prepared in example 1 of the present invention;
FIG. 2 is a UV diagram of water-soluble tantalum nanoparticles prepared in examples 1 and 4 of the present invention;
FIG. 3 is an XRD pattern of water-soluble tantalum nano particles prepared in example 1 and example 4 according to the invention;
FIG. 4 is an XPS electron energy spectrum of the tantalum nanoparticle obtained in example 1;
FIG. 5 is an XPS electron energy spectrum of the tantalum nanoparticle obtained in example 4;
FIG. 6 is an infrared spectrum of the tantalum powder as a raw material, the water-soluble tantalum nano particles prepared in test example 1 and sodium hexametaphosphate;
FIG. 7 is a TEM image of water-soluble tantalum nanoparticles prepared at 300r/min for both the first and second ball milling speeds;
FIG. 8 is a TEM image of water-soluble tantalum nanoparticles prepared at 600r/min for both the first and second ball milling speeds.
Detailed Description
The following detailed description of preferred embodiments of the invention is made in connection with the accompanying drawings, which form a part hereof, and together with the description of the embodiments of the invention, are used to explain the principles of the invention and are not intended to limit the scope of the invention.
The invention discloses a preparation method of water-soluble tantalum nano particles, which comprises the following steps:
(1) Dissolving tantalum powder in water, performing ultrasonic treatment, and centrifuging to obtain refined tantalum powder;
(2) Mixing the refined tantalum powder with metaphosphate to obtain a first mixture;
(3) Performing first-stage ball milling on the first mixture to obtain a first mixture subjected to first-stage ball milling;
(4) Adding a proper amount of water into the first mixture subjected to the first-stage ball milling treatment in the step (3), and then adding NaH 2 PO 4 And (3) performing ball milling treatment at the second stage until the pH value of the solution is 5.5-6.5, centrifuging and cleaning to obtain the water-soluble tantalum nano particles.
Compared with the prior art, the preparation method of the water-soluble tantalum nano particles is provided with metaphosphate, and the covalent bond of the tantalum oxide on the surface of the water-soluble tantalum powder is broken to form tantalate under the combined action of metaphosphate and high-energy ball milling in the first ball milling stage, so that the surface charge of the tantalate is improved, and the solubility of the tantalate is increased; and water is added in the second ball milling stage for wet milling treatment, so that the crushing efficiency of ball milling on large-particle tantalum is improved, meanwhile, metaphosphate can form a colloid state after absorbing water and is coated on the surface of tantalum nano particles, the stability of the tantalum nano particles in a high-water solution is improved, and the stability time in the water solution with the concentration of 60mg/mL is at least 48 hours.
In the invention, the purchased commercial tantalum powder is subjected to ultrasonic pretreatment, so that the particle diameter of the tantalum powder is thinned, and the dispersibility of the water-soluble tantalum nano particles is improved. Adopting low-speed 2000-4000r/min centrifugal screening to remove tantalum powder with larger particle size, and then carrying out high-speed 10000-11000r/min centrifugal collection of refined tantalum powder, wherein the particle size of the refined tantalum powder is less than 190nm.
Specifically, naH 2 PO 4 The concentration of the solution is 0.02-0.1g/ml.
Specifically, the ultrasonic time is 1-2h, such as 1.2h, 1.4h, 1.6h, 1.8h, 2.0h, and the ultrasonic power is 280-320W, such as 280W, 290W, 300W, 310W, 320W.
Specifically, the metaphosphate in the step (2) is one or more of sodium trimetaphosphate, sodium tetrametaphosphate and sodium hexametaphosphate.
In the step (2), the first mixture may be directly mixed with the refined tantalum powder, or may be prepared by dissolving the metaphosphate in a proper amount of secondary water and mixing with the refined tantalum powder.
Specifically, the mass ratio of the metaphosphate to the refined tantalum powder in the step (2) is 0.1-1.2.
Exemplary mass ratios of metaphosphate to refined tantalum powder are 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2.
It should be noted that, through a great deal of experiments, the inventors found that when the mass ratio of metaphosphate to refined tantalum powder is lower than 0.1, the modification effect is not obvious, the stability in aqueous solution is relatively poor, the modification effect is firstly increased and then reduced within the range of 0.1-1.2, and the modification effect is 1: the peak is reached at 1, and the modification effect is better at more than 1.2, but the mass ratio is selected comprehensively to be 0.1-1.2 unlike the previous range.
Specifically, the ball milling rotating speed in the ball milling treatment of the first stage in the step (3) is 100-600r/min, and the ball milling time is 1-3h.
Illustratively, the ball milling speeds in the first stage ball milling treatment are 100r/min, 200r/min, 300r/min, 400r/min, 500r/min, 600r/min, and the ball milling times are 1h, 1.5h, 2h, 2.5h, 3h.
Under the first stage ball milling treatment condition, the extrusion force of the ball milling beads promotes the tantalum nano particles and the metaphosphate to form a mixture in a cross existence mode, and meanwhile, the high-energy ball milling treatment mode activates the surface of the material, promotes the reaction of phosphate groups and the tantalum oxide film on the surface of the tantalum nano particles, so that the covalent bond of the tantalum oxide film on the surface of the water-soluble tantalum nano particles is broken to form tantalate, the surface charge of the tantalate is improved, and the solubility of the tantalate is improved.
Specifically, medical auxiliary materials are also added into the water in the step (4).
Specifically, the medical auxiliary material is one or more of polyvinylpyrrolidone, polyethylene glycol 4000, polyethylene glycol 6000, betaine, glucoside, polylactic acid, chitosan, phospholipids or tween.
The biocompatible medical auxiliary material enables the synthesized water-soluble tantalum nano particles to keep good dispersibility and stability in organisms, the medical auxiliary material and metaphosphate are coated on the surfaces of the tantalum nano particles, when the medical auxiliary material is selected to be various, the medical auxiliary material exists in a mixed coating mode instead of a one-layer coating mode, and the coating mode has the advantages of various medical auxiliary materials at the same time, and has good biocompatibility while improving the repulsive force of surface charges.
Specifically, the concentration of the medical auxiliary material in water in the step (4) is 0.5-1g/mL, and the mass ratio of the medical auxiliary material to the refined tantalum powder is 0.5-1.2.
Illustratively, the concentration of the medical auxiliary material in the second mixture is 0.5g/mL, 0.6g/mL, 0.7g/mL, 0.8g/mL, 0.9g/mL, 1.0g/mL, and the mass ratio of the medical auxiliary material to the refined tantalum powder is 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2.
A large number of experiments show that the addition of the medical auxiliary materials can improve the stability of the tantalum nano particles in the PBS buffer solution, and the tantalum nano particles can stably exist in the PBS buffer solution for at least 8 hours, and the inventor discovers that when the addition of the medical auxiliary materials is too small, the stability effect of the tantalum nano particles in the PBS solution is not obvious, when the addition is too large, the agglomeration phenomenon can be accelerated, and the concentration of the medical auxiliary materials in water is 0.5-1g/mL.
Specifically, the ball milling rotating speed in the second stage ball milling treatment in the step (4) is 100-600r/min, and the ball milling time is 2-6h.
Illustratively, the ball milling rotational speed in the second stage ball milling treatment is 100r/min, 200r/min, 300r/min, 400r/min, 500r/min, 600r/min, and the ball milling time is 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h.
In the step (4), a proper amount of water is added to fully infiltrate the first mixture subjected to the ball milling in the first stage. Under the condition of the second stage ball milling treatment of the invention, the method comprises the steps of adding a proper amount of inorganic salt solution (NaH 2 PO 4 Solution) to pH 5.5-6.5, can inhibit the hydrolysis of metaphosphate, improve the utilization rate of metaphosphate, reduce the agglomeration phenomenon, improve the stability of the solution, increase the electric charge on the surface of water-soluble tantalum nano particles, and the biocompatible medical auxiliary material is in a macromolecular chain shape, and the chain macromolecules are vigorously mixed in the ball milling process to form a crossed and staggered network structure.
The mesh structure has two advantages, namely more medical auxiliary materials can be coated on the tantalum nano particles, and the biocompatibility is improved; secondly, the loading of metaphosphate can be carried out through a reticular structure, so that the solution stability is improved. Through wet milling treatment in the second stage, the crushing efficiency of ball milling on large-particle tantalum is improved, meanwhile, metaphosphate can form a colloid state after absorbing water, a long chain state is presented, the long chain is coated on the surface layer of tantalum nano particles to form a hydrophilic film, the hydrophilic film is negatively charged, the agglomeration phenomenon is reduced through the repulsive interaction of electrostatic force, and the stability of water-soluble tantalum nano particles is improved.
Specifically, the centrifugation in step (4) is specifically: centrifuging at 2000-3000r/min for 4-6min, and centrifuging at 10000-11000r/min for 10-15min.
The unstable large-particle water-soluble tantalum nanoparticles are removed by low-speed centrifugation, and then unmodified medical auxiliary materials or metaphosphate are removed by high-speed centrifugation.
Specifically, the tantalum nanoparticle storage method provided by the invention comprises the steps of adding a proper amount of sodium hyaluronate, and freeze-drying for later use.
In another embodiment of the invention, a water-soluble tantalum nanoparticle prepared by the method is provided, wherein the water-soluble tantalum nanoparticle is spherical and has a diameter of 30-60nm.
The water-soluble tantalum nano particles prepared by the method are spherical under the nanoscale, have the size of 30-60nm and are in a monodisperse state.
Specifically, the water-soluble tantalum nano particles are coated with a layer of hydrophilic film, and the thickness of the hydrophilic film is 4-6nm.
It should be noted that the hydrophilic membrane is a mixed complex of metaphosphate and medical auxiliary material or a metaphosphate single complex, and the complex can improve the biostability of the water-soluble tantalum nano-particles, and can be coupled with more metaphosphate long chains to improve the surface charge of the water-soluble tantalum nano-particles.
In another embodiment of the invention, the application of the water-soluble tantalum nano particles in preparing a radiotherapy sensitizer is provided.
The water-soluble tantalum nanoparticles of the present invention can be stable in aqueous solution for at least 48 hours and in PBS buffer for at least 8 hours. The water-soluble tantalum nano particles have better biocompatibility and high X-ray attenuation coefficient, and can play a role in radiotherapy sensitization.
Example 1
The preparation method of the water-soluble tantalum nano particles of the embodiment comprises the following steps:
(1) Dissolving 5g of commercial tantalum powder in 500mL of water, performing ultrasonic dispersion for 1h to obtain a tantalum powder solution, adding 0.5L of water into the tantalum powder solution, performing ultrasonic treatment, performing low-speed centrifugation at the ultrasonic power of 300W for 1h at 2000-4000r/min to remove large-particle-size tantalum nano particles, and performing high-speed centrifugation at 10000-11000r/min to obtain refined tantalum powder;
(2) Mixing 2.5g of refined tantalum powder and 1.0g of sodium hexametaphosphate to obtain a first mixture;
(3) Placing the first mixture into an agate tank, and ball milling for 1h at 600r/min to obtain a first mixture subjected to ball milling treatment in a first stage;
(4) Adding 4mL of secondary water to the first mixture subjected to the first-stage ball milling in the step (3), and adding an appropriate amount of 0.1g/mL NaH 2 PO 4 And (3) adjusting the pH value of the solution to 5.5-6.5, ball milling for 3 hours at 600r/min, centrifuging at 2000r/min for 6min at a low speed to remove unstable water-soluble tantalum nano particles, centrifuging at 10000r/min for 15min at a high speed to clean, dissolving in secondary water after cleaning for 3-4 times, and cross-cleaning by using water and alcohol in the centrifuging process to ensure that impurities are cleaned cleanly, thereby obtaining the water-soluble tantalum nano particles.
The water-soluble nano particles prepared in the embodiment are dissolved in a proper amount of water, are uniformly dispersed by 300W ultrasonic waves, are added with a proper amount of sodium hyaluronate, are uniformly mixed by ultrasonic waves and are freeze-dried to obtain the freeze-dried powder of the water-soluble nano particles, and are placed in a constant-temperature moisturizing cabinet for standby.
The TEM image of the water-soluble tantalum nanoparticle prepared in this example is shown in fig. 1, and it can be seen from the image that the water-soluble tantalum nanoparticle prepared in this example is spherical, has a size of 30-60nm, and exhibits a monodisperse state. The water-soluble tantalum nano particles of the embodiment are coated with a layer of hydrophilic film, and the thickness of the hydrophilic film is 4-6nm.
Example 2
The preparation method of the water-soluble tantalum nano particles of the embodiment comprises the following steps:
(1) Dissolving commercial tantalum powder in water, performing ultrasonic dispersion for 1.5 hours, centrifuging at a low speed with ultrasonic power of 320W and 2000-4000r/min to remove large-particle-size tantalum nano particles, and centrifuging at a high speed of 10000-11000r/min to obtain refined tantalum powder;
(2) Mixing refined tantalum powder and sodium tetrametaphosphate, wherein the mass ratio of the sodium tetrametaphosphate to the refined tantalum powder is 0.1, so as to obtain a first mixture;
(3) Placing the first mixture into an agate tank, and ball milling for 3 hours at 100r/min to obtain a first mixture subjected to ball milling treatment in a first stage;
(4) Adding 4mL of secondary water to the first mixture subjected to the first-stage ball milling in the step (3), and adding an appropriate amount of 0.05g/mL NaH 2 PO 4 The pH of the solution is regulated to 5.5-6.5, ball milling is carried out for 6 hours at 100r/min, firstly, unstable water-soluble tantalum nano particles are removed by low-speed centrifugation at 2500r/min for 5min, washing is carried out by centrifugation at 10500r/min for 13min, the washing is carried out for 3-4 times and then the washing is carried out in secondary water, water and alcohol are used for cross washing in the centrifugation process, and impurities are ensured to be washed cleanly, thus obtaining the water-soluble tantalum nano particles.
The water-soluble nano particles prepared in the embodiment are dissolved in a proper amount of water, are uniformly dispersed by 300W ultrasonic waves, are added with a proper amount of sodium hyaluronate, are uniformly mixed by ultrasonic waves and are freeze-dried to obtain the freeze-dried powder of the water-soluble nano particles, and are placed in a constant-temperature moisturizing cabinet for standby.
The water-soluble tantalum nano particles prepared in the embodiment are spherical, have the size of 30-60nm and are in a monodisperse state. The water-soluble tantalum nano particles of the embodiment are coated with a layer of hydrophilic film, and the thickness of the hydrophilic film is 4-6nm.
Example 3
The preparation method of the water-soluble tantalum nano particles of the embodiment comprises the following steps:
(1) Dissolving commercial tantalum powder in water, performing ultrasonic dispersion for 2 hours, centrifuging at a low speed with ultrasonic power of 280W and 2000-4000r/min to remove large-particle-size tantalum nano particles, and centrifuging at a high speed of 10000-11000r/min to obtain refined tantalum powder;
(2) Mixing refined tantalum powder and sodium trimetaphosphate, wherein the mass ratio of the sodium trimetaphosphate to the refined tantalum powder is 0.6, so as to obtain a first mixture;
(3) Placing the first mixture into an agate tank, and ball milling for 2 hours at 350r/min to obtain a first mixture subjected to ball milling treatment in a first stage;
(4) Adding 4mL of secondary water to the first mixture subjected to the first-stage ball milling in the step (3), and adding an appropriate amount of 0.02g/mNaH of l 2 PO 4 The pH of the solution is regulated to 5.5-6.5, ball milling is carried out for 4 hours at 350r/min, firstly, unstable water-soluble tantalum nano particles are removed by low-speed centrifugation at 3000r/min for 4min, washing is carried out by centrifugation at 11000r/min for 10min, the washing is carried out for 3-4 times and then the washing is carried out in secondary water, water and alcohol are used for cross washing in the centrifugation process, and impurities are ensured to be washed cleanly, thus obtaining the water-soluble tantalum nano particles.
The water-soluble nano particles prepared in the embodiment are dissolved in a proper amount of water, are uniformly dispersed by 300W ultrasonic waves, are added with a proper amount of sodium hyaluronate, are uniformly mixed by ultrasonic waves and are freeze-dried to obtain the freeze-dried powder of the water-soluble nano particles, and are placed in a constant-temperature moisturizing cabinet for standby.
The water-soluble tantalum nano particles prepared in the embodiment are spherical, have the size of 30-60nm and are in a monodisperse state. The water-soluble tantalum nano particles of the embodiment are coated with a layer of hydrophilic film, and the thickness of the hydrophilic film is 4-6nm.
Example 4
The water-soluble nanoparticle of this example was prepared in the same manner as in example 1, except that polyvinylpyrrolidone was added to the secondary water in step (4), specifically, 2g of polyvinylpyrrolidone was added to 4mL of secondary water, and after 300W of ultrasonic treatment was performed until complete dissolution, naH was added 2 PO 4 Solution.
The water-soluble tantalum nano particles prepared in the embodiment are spherical, have the size of 30-60nm and are in a monodisperse state. The water-soluble tantalum nano particles of the embodiment are coated with a layer of hydrophilic film, and the thickness of the hydrophilic film is 4-6nm.
Example 5
The water-soluble nanoparticle of this example is the same as the preparation method of example 1, except that polylactic acid is added into the secondary water in step (4), specifically, the concentration of polylactic acid in water is 1g/mL, the mass ratio of polylactic acid to refined tantalum powder is 1.2, and NaH is added after the ultrasonic treatment of 300W until the polylactic acid is completely dissolved 2 PO 4 Solution.
The water-soluble tantalum nano particles prepared in the embodiment are spherical, have the size of 30-60nm and are in a monodisperse state. The water-soluble tantalum nano particles of the embodiment are coated with a layer of hydrophilic film, and the thickness of the hydrophilic film is 4-6nm.
Example 6
The preparation method of the water-soluble nanoparticle of the embodiment is the same as that of the embodiment 1, except that polyethylene glycol 4000 is added into the secondary water in the step (4), specifically, the concentration of the polyethylene glycol 4000 in the water is 0.5g/mL, the mass ratio of polylactic acid to refined tantalum powder is 0.5, and NaH is added after the ultrasonic treatment of 300W until the polylactic acid and the refined tantalum powder are completely dissolved 2 PO 4 Solution.
The water-soluble tantalum nano particles prepared in the embodiment are spherical, have the size of 30-60nm and are in a monodisperse state. The water-soluble tantalum nano particles of the embodiment are coated with a layer of hydrophilic film, and the thickness of the hydrophilic film is 4-6nm.
Comparative example 1
The tantalum nanoparticle of this comparative example was prepared in the same manner as in example 1, except that the first mixture and water were directly mixed in step (4), and only one ball milling treatment, i.e., ball milling at 600r/min for 1 hour was performed, without performing the second stage ball milling treatment.
Test example 1
1. The UV images of the water-soluble tantalum nanoparticles prepared in example 1 and example 4 are shown in fig. 2, and it can be seen from fig. 2 that the infrared light absorption of the tantalum nanoparticles after adding PVP is better than that of the tantalum nanoparticles modified by single modification, and the absorbance of the tantalum nanoparticles modified by PVP in the infrared region is about 1.5 times that of the tantalum nanoparticles modified by single modification, so that the tantalum nanoparticles have better photo-thermal conversion capability, that is, better photo-thermal treatment effect can be obtained after adding PVP.
2. XRD of the water-soluble tantalum nanoparticles prepared in example 1 and example 4 and the raw tantalum powder are shown in figure 3, and XRD analysis shows that the components and structures of the water-soluble nanoparticles are not obviously changed compared with those of the original nanoparticles, so that the original components and structures are maintained, and the method disclosed by the invention cannot change the components and structures of the tantalum nanoparticles.
3. FIG. 4 shows XPS electron spectrum of the tantalum nano-particles obtained in example 1Fig. 5 is an XPS electron energy spectrum of the tantalum nanoparticle obtained in example 4. XPS electron spectrum is to analyze the surface component of the material, ta4f is one peak most commonly used in XPS analysis, ta4f5/2 and Ta4f7/2 are two split peaks of Ta4f, the valence state and component of tantalum element are judged by the combination energy of the positions of the split peaks, and the results in FIGS. 4 and 5 show that the component is Ta 2 O 5 And TaO 3 - The chemical bond change on the surface of the tantalum nano particle is shown, and the surface tantalum oxide reacts with sodium hexametaphosphate, so that the water solubility is improved.
4. The infrared spectra of the tantalum powder as a raw material, the prepared water-soluble tantalum nanoparticle and sodium hexametaphosphate in test example 1 are shown in fig. 6. The figure shows that the spectrogram of the tantalum nano particles after ball milling has the characteristics of the spectrogram of tantalum before ball milling and the spectrogram of sodium hexametaphosphate, and the change of the external spectrum of the water-soluble tantalum nano particles obtained by the method shows that sodium hexametaphosphate is successfully modified on the tantalum nano particles.
Test example 2
The water-soluble tantalum nanoparticles prepared in examples 1 to 6 and comparative example 1 were prepared into solutions with a concentration of 60mg/mL by adding water and PBS buffer, respectively, and the changes in the concentrations with time were observed, and when the concentrations were rapidly decreased, the stability of the solutions was decreased, the time for stabilizing the solutions was determined, and the stability time of each group was examined, and the results are shown in Table 1.
TABLE 1
As can be seen from Table 1, the water-soluble tantalum nanoparticles prepared by the method have better stability in high concentrations of aqueous solution and PBS buffer solution, and the stability time of comparative example 1 is obviously lower than that of example 1, because the secondary ball milling improves the crushing efficiency of ball milling on large-particle tantalum, and the metaphosphate can form a colloid state after absorbing water and is coated on the surface of the tantalum nanoparticles, thereby improving the stability of the aqueous solution of the tantalum nanoparticles.
In addition, examples 4-5 do not differ much in the stabilization time of the tantalum nanoparticles in aqueous solution compared to example 1, indicating that the stability of the tantalum nanoparticles in water is not affected by the addition ratio of the medical auxiliary material in the present invention. However, compared with examples 1-3, the stability time of the tantalum nanoparticles in the PBS buffer solution is obviously improved, because the addition of the medical auxiliary material can ensure that the synthesized water-soluble tantalum nanoparticles can keep good dispersibility and stability in organisms, the medical auxiliary material and the metaphosphate are coated on the surfaces of the tantalum nanoparticles together, and the medical auxiliary material exists in a mixed coating mode instead of a one-layer coating mode, and the coating mode has the advantages of various surfactants, improves the surface charge repulsion and has good biocompatibility, so that the requirement of using the water-soluble tantalum nanoparticles in the PBS buffer solution can be met.
Test example 3
Only the rotational speed of the first ball milling and the rotational speed of the second ball milling are changed, the mass ratio of the refined tantalum powder to the sodium hexametaphosphate is 1:1, and the water-soluble tantalum nano particles are prepared in the same way as in the example 1.
The stability time of the water-soluble tantalum nanoparticles in an aqueous solution was measured as in test example 2 by preparing the tantalum nanoparticles into a 60mg/mL aqueous solution, and the results are shown in Table 2.
TABLE 2
As can be seen from table 2, the stability increases with increasing rotation speed, however, TEM images of water-soluble tantalum nanoparticles prepared at 300r/min and 600r/min are shown in fig. 7 and 8, respectively, and as can be seen from fig. 7 and 8, the ratio of the nanoparticles decreases with increasing rotation speed, and the first ball milling rotation speed and the second ball milling rotation speed in the present invention are selected to be optimal at 300r/min in consideration of the stability and the spherical ratio.
The present invention is not limited to the above-mentioned embodiments, and any changes or substitutions that can be easily understood by those skilled in the art within the technical scope of the present invention are intended to be included in the scope of the present invention.
Claims (10)
1. A method for preparing water-soluble tantalum nano particles, which is characterized by comprising the following steps:
(1) Dissolving tantalum powder in water, performing ultrasonic treatment, and centrifuging to obtain refined tantalum powder;
(2) Mixing the refined tantalum powder with metaphosphate to obtain a first mixture;
(3) Performing first-stage ball milling on the first mixture to obtain a first mixture subjected to first-stage ball milling;
(4) Adding a proper amount of water into the first mixture subjected to the first-stage ball milling treatment in the step (3), and then adding NaH 2 PO 4 And (3) performing ball milling treatment at the second stage until the pH value of the solution is 5.5-6.5, centrifuging and cleaning to obtain the water-soluble tantalum nano particles.
2. The method for preparing water-soluble tantalum nano-particles according to claim 1, wherein said metaphosphate in said step (2) is one or more of sodium trimetaphosphate, sodium tetrametaphosphate and sodium hexametaphosphate.
3. The method for producing water-soluble tantalum nanoparticles according to claim 1 or 2, wherein the mass ratio of metaphosphate to refined tantalum powder in step (2) is 0.1 to 1.2.
4. The method for preparing water-soluble tantalum nanoparticles according to claim 1, wherein the ball milling speed in the first stage ball milling treatment in step (3) is 100-600r/min and the ball milling time is 1-3h.
5. The method for preparing water-soluble tantalum nano particles according to claim 1, wherein medical auxiliary materials are added into the water in the step (4), and preferably, the medical auxiliary materials are one or more of polyvinylpyrrolidone, polyethylene glycol 4000, polyethylene glycol 6000, betaine, glucoside, polylactic acid, chitosan, phospholipids or tween.
6. The method for preparing water-soluble tantalum nano particles according to claim 5, wherein the concentration of the medical auxiliary material in water is 0.5-1g/mL, and the mass ratio of the medical auxiliary material to the refined tantalum powder is 0.5-1.2.
7. The method for preparing water-soluble tantalum nano particles according to claim 1, wherein the ball milling rotation speed in the second stage ball milling treatment in the step (4) is 100-600r/min, and the ball milling time is 2-6h;
the centrifugation specifically comprises: centrifuging at 2000-3000r/min for 4-6min, and centrifuging at 10000-11000r/min for 10-15min.
8. A water-soluble tantalum nanoparticle prepared by the method of any one of claims 1-7, wherein said water-soluble tantalum nanoparticle is spherical and has a diameter of 30-60nm.
9. The water-soluble tantalum nanoparticle according to claim 8, wherein said water-soluble tantalum nanoparticle is coated with a hydrophilic film having a thickness of 4-6nm.
10. Use of water-soluble tantalum nanoparticles prepared by the method of any one of claims 1-7 in the preparation of a radiosensitizer.
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