CN105288743A - Radionuclide-labeled mesoporous bioglass nanoparticle and its preparation method and application - Google Patents
Radionuclide-labeled mesoporous bioglass nanoparticle and its preparation method and application Download PDFInfo
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- CN105288743A CN105288743A CN201410353907.6A CN201410353907A CN105288743A CN 105288743 A CN105288743 A CN 105288743A CN 201410353907 A CN201410353907 A CN 201410353907A CN 105288743 A CN105288743 A CN 105288743A
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- mesoporous bioglass
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Abstract
The invention discloses a mesoporous bioglass nanoparticle radionuclide-labeled product and its preparation method and application. This product may be prepared in following steps: preparing a sol solution containing radionuclide 45Ca; preparing a mesoporous bioglass nanoparticle containing the radionuclide 45Ca; subjecting the mesoporous bioglass nanoparticle containing the radionuclide 45Ca to amination surface modification by using a silane coupling agent. The radionuclide 45Ca has a suitable half-time: 163.5 days. The radionuclide-labeled mesoporous bioglass nanoparticle provided by the invention has the advantages that the effect in labeling mesoporous bioglass nanoparticles can be given, the in-vivo distribution and accumulation condition of the mesoporous bioglass nanoparticles can be quantitatively and visually detected, and this nanoparticle is suitable for use in the study on the in-vino absorption and biological distribution of bioglass stents.
Description
Technical field
The present invention relates to a kind of mesoporous bioglass nano-particle, mesoporous bioglass nano-particle particularly relating to a kind of radioisotope labeling and preparation method thereof and application.
Background technology
Mesoporous bioglass (mesoporousbioactiveglass, MBG) nano-particle is with SiO
2-CaO-P
2o
5based on constituent, there is the novel nano-material of the mesoporous channel design of high-sequential.At present, by adding different surfactants (as cetab in evaporation-induced self-assembly course of reaction, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer etc.) the mesoporous bioglass nano-particle of mesopore size within the scope of 2-10nm can be prepared, the scope of its specific surface area is at 300-1040m
2/ g, pore volume can reach 0.36-1.54cm
3/ g is the decades of times of traditional biological glass.Mesoporous bioglass nano-particle has the special performance of nano material, shows good characteristic and the new functions such as size is little, specific surface area is large, surface activity is high, high adsorption capacity, and can act on particular tissues and cell selectively.Therefore, have research using mesoporous bioglass nano-particle as carrier, be applied to the research and development of slow releasing pharmaceutical; Also research is had by mesoporous bioglass nano-particle for the diagnosis and treatment of various tumor.In addition, mesoporous bioglass nano-particle not only has good biocompatibility and biological activity, also has small-size effect and the skin effect of nano material uniqueness.After mesoporous bioglass nano-particle is implanted in osseous tissue, firmly chemical bonds can be formed with osseous tissue, and there is osteoinductive.This nano material is also one of the emphasis and focus of bone renovating material research at present.
Along with the development of nanotechnology, nano material will be increasingly extensive in the application of biomedical sector, and the biosafety issues about nano material also will be valued by the people gradually.And study the biological safety of nano material, with regard to being necessary, spike is carried out to the application of nano material in body, to study the biodistribution of nano material metabolism in body and to evaluate nano material to the impact of body function.The important method that radioisotope labeling is biodistribution in research nano material body is carried out to nano material.In addition, by the radioisotope labeling to mesoporous bioglass nano-particle, basis can be provided for exploitation with medicine, bone renovating material etc. that mesoporous bioglass nano-particle is carrier.
The technology of preparing setting up a kind of mesoporous bioglass nano-particle of radioisotope labeling is key and the prerequisite of research work.Mesoporous bioglass nano-particle is main constituent with calcium-silicon matrix, and the isotope element of conventional silicon (
31si) half-life is 170 minutes, relatively short; And calcium isotope (
45ca) half-life is then 163.5 days.In addition, Calcium compounds is constituent important in MBG, and this mainly can regulate the radius of curvature of surperficial activity gel bundle due to the change of Calcium compounds, thus affects the meso-hole structure of mesoporous bioglass.Therefore, select
45ca effectively can avoid from labeled in situ synthesis MBG support the problem destroying meso-hole structure because adopting the introducing of exogenous nucleic.Meanwhile,
45ca discharges β ray, and its energy is 0.26MeV, possesses more stable organizational standard curve and the response rate, adopts homogeneous liquid scintillation technique can carry out Accurate Determining to its radioactivity.Therefore, selection is only had
45ca carries out labeled in situ as radionuclide to mesoporous bioglass nano-particle, is just expected to reach disclose degradation characteristic and chorologic expection object in alloy granular solids.
Silane coupler is kind of a low molecule silanes with special construction, is also kind of an important inorganic nanoparticles surface modifying material.The general formula of silane coupler is that RSiX3, R represent the groups such as amino, sulfydryl, vinyl, epoxy radicals, cyano group and methyl-prop ethylene acyloxy, and X represents the group that can be hydrolyzed, as halogen, alkoxyl, acyloxy etc.Silane coupler is mainly realized by formation chemical bond the surface modification of inorganic nano material.There is hydroxyl in mesoporous bioglass nano grain surface, it can form chemical bonds with groups such as the alkoxyl in silane coupler, acyloxy, thus more stable marked product can be obtained, in further mesoporous bioglass alloy granular solids, video picture and biodistribution research provide investigative technique support.
Summary of the invention
The invention provides a kind of mesoporous bioglass nano-particle of radioisotope labeling, wherein, adopt radionuclide to carry out labelling to mesoporous bioglass nano-particle, described radionuclide is
31si,
32p,
45any one or a few combination in Ca.
Preferably, described radionuclide is
45ca.
Preferably, the composition of the mesoporous bioglass porous support of described radioisotope labeling comprises CaO, SiO
2and P
2o
5, wherein, the mol ratio of Ca, Si and P is (1-30): (50-100): (1-10).
Preferably, the mol ratio of Ca, Si and P is 15:80:5.
Preferably, described mesoporous bioglass nano-particle size dimension is the spherical of 50-100nm.
Preferably, the mesoporous size of described mesoporous bioglass nano-particle is 2.5nm.
Present invention also offers a kind of preparation method of mesoporous bioglass nano-particle of above-mentioned radioisotope labeling, comprise the following steps:
Step a, prepares precursor sol liquid: by silicon source, calcium source, phosphorus source and surfactant dissolves in a solvent, stirs and joins in politef reactor after 12 hours, under 80 DEG C of conditions, carry out hydration reaction 48h under alkali condition.Wherein, in described calcium source, silicon source and phosphorus source, the mol ratio of Ca, Si and P is 15:80:5, wherein:
The silicon source containing radionuclide of at least trace quantity is contained in described silicon source, and/or
The calcium source containing radionuclide of at least trace quantity is contained in described calcium source, and/or
The phosphorus source containing radionuclide of at least trace quantity is contained in described phosphorus source;
Step b, sinters 5 hours by the 550 DEG C of temperature of the precursor liquid after step b process, obtains the mesoporous bioglass nano-particle of described radioisotope labeling.
Step c, obtains after being sintered by step b
45the mesoporous bioglass nano-particle of Ca labelling joins silane coupler dilute solution, makes its silane amination.
Preferably, described silicon source is positive silicate class.
Preferably, described silicon source is selected from least one in ethyl orthosilicate, methyl silicate and positive silicic acid propyl ester;
Preferably, described calcium source is inorganic calcium.
Preferably, described calcium source is selected from least one in lime nitrate, calcium acetate and its hydrate.
Preferably, described phosphorus source is organophosphorus compounds.
Preferably, described phosphorus source is selected from least one in trimethyl phosphate and triethyl phosphate.
Preferably, described surfactant is cationic surfactant.
Preferably, described cationic surfactant is selected from CTAB.
The present invention, owing to have employed above technical scheme, has significant technique effect:
The mesoporous bioglass nano-particle of radioisotope labeling provided by the invention, effectively can carry out labelling to mesoporous bioglass nano-particle, quantitatively and intuitively can detect distribution in vivo and the accumulation situation of mesoporous bioglass nano-particle, may be used for the body absorption of bio-vitric support and chorologic research.
Accompanying drawing explanation
Fig. 1 is the qualification result figure of silica gel thin-layer paper chromatography (ITLC/SG method) marked product of embodiment 1 gained mesoporous bioglass nano-particle;
Fig. 2 is transmission electron microscope (TEM) figure of embodiment 1 gained mesoporous bioglass nano-particle;
Fig. 3 is FTIR spectrum (FTIR) figure of embodiment 1 gained mesoporous bioglass nano-particle;
Fig. 4 is scanning electron microscope (SEM) figure of embodiment 1 gained mesoporous bioglass nano-particle.
Detailed description of the invention
Radioisotope labeling tracer technique utilizes the compound of radionuclide or its labelling as tracer, application ray detects the distribution of tracer, and the method for qualitative, quantitative observation analysis is carried out in conjunction with autoradiography, microscopic examination counting, liquid scintillation counter etc., have highly sensitive, method is easy, positioning and quantitative feature accurately, therefore, adopt radioisotope labeling tracer technique to carry out labelling mesoporous bioglass nano-particle, important technological means can be provided for the bio distribution of nano-particle and in-vivo imaging research.
Mesoporous bioglass nano-particle is main constituent with calcium-silicon matrix, and the isotope element of conventional silicon (
31si) half-life is 170 minutes, relatively short; And calcium isotope (
45ca) half-life is then 163.5 days, and
45ca discharges β ray, and its energy is 0.26MeV, possesses more stable organizational standard curve and the response rate, adopts homogeneous liquid scintillation technique can carry out Accurate Determining to its radioactivity.Therefore, select
45ca carries out labeled in situ as radionuclide to mesoporous bioglass nano-particle, is the key problem in technology effectively disclosing bio distribution and accumulation situation in alloy granular solids.
1-4 with reference to the accompanying drawings, the present invention is described in more detail with the following Examples, to understand the present invention better.
Embodiment 1
(1) containing radionuclide
45the preparation of Ca sol solutions
First Chile saltpeter is utilized, containing trace quantity
45caCl
2calcium chloride change into containing trace quantity
45ca (NO
3)
24H
2the calcium nitrate tetrahydrate of O, then add surplus calcium nitrate tetrahydrate, make the total amount of calcium nitrate tetrahydrate be 1.1g.Then 0.56g triethyl phosphate (TEP), 5.22g ethyl orthosilicate (TEOS), 0.46g sodium hydroxide, the cetyl trimethyl ammonium bromide (CTAB) of 1.4g and the polyvinylpyrrolidone (PVP) of 1g is added respectively, stirring and dissolving is (in solution, the mol ratio of Si, Ca and P is 80:15:5) in the deionized water of 120ml, room temperature reaction joins after 12 hours in politef reactor, carries out hydration reaction 48 hours at 80 DEG C.
Wherein, reagent calcium nitrate tetrahydrate, triethyl phosphate, ethyl orthosilicate, cetyl trimethyl ammonium bromide and polyvinylpyrrolidone are all purchased from Sigma.
(2) containing radionuclide
45the preparation of the mesoporous bioglass nano-particle of Ca
Sinter under air ambient after the product ethanol obtained after hydration reaction washes 3 times, sintering temperature is 550 DEG C, and sintering time is 5 hours, and sintering heating rate is 5 DEG C of min
-1.After cooling, namely obtain with
45the mesoporous bioglass nano-particle of Ca labelling.
(3) containing radionuclide
45the silane amination of the mesoporous bioglass nano-particle of Ca
Will containing radionuclide
45the mesoporous bioglass nano-particle of Ca is placed in ethanol solution, ultrasonic 30min under 59KHz frequency, repeatedly cleans rear for subsequent use with dehydrated alcohol.Take out 90mL alcoholic solution and (include 200mg radionuclide
45the mesoporous bioglass nano-particle of Ca labelling), and add 10mL
(molecular formula is (3-aminopropyl) triethoxysilane: H
2n (CH
2)
3si (OC
2h
5)
3) solution (coupling agent: ethanol=1:5, V/V), the stirred in water bath of 60 DEG C reacts 4 hours, and keeps reacting solution pH value to be 8.After reaction terminates, by washing with alcohol, vacuum drying obtains amino modified containing radionuclide
45the mesoporous bioglass nano-particle of Ca.
Silica gel thin-layer paper chromatography (ITLC/SG method) is adopted to identify to the qualification of gained mesoporous bioglass nanoparticle label product.With Flash silica thin layer chromatography paper (ITLC/SG) for carrier, launch with normal saline, then every bar chromatographic paper is cut into the equidistant little paper slip of 1cm, puts into radiometry test tube and measure.Result as shown in Figure 1,
45ca-Rf value is all in 0.80 ~ 1.00 scope, and the mesoporous bioglass nano-particle Rf value of labelling is 0.00, motionless at paper chromatography bar initial point.Through marked product radio-chemical purity >=95% obtained by above method qualification.
Carry out tem observation to gained mesoporous bioglass nano-particle, as shown in Figure 2, visible nanochannel structure, granular size is of a size of 50-100nm to result.FTIR observes gained mesoporous bioglass nano-particle, result as shown in Figure 3, the infrared curve 2979.4cm of modified nano-particle
-1having there is the characteristic absorption peak of coupling agent in place, illustrates that coupling agent receives nano grain surface.It is spherical in shape that SEM observes visible mesoporous bioglass nano-particle, the meso-hole structure that surface is certain as seen.
The present embodiment selects radionuclide
45ca, it has the suitable half-life, is 163.5 days, may be used for mesoporous bioglass nano-particle and absorbs in vivo and chorologic research.Radioactive pollution is easy to control and process.Pass through radionuclide
45ca quantitatively and intuitively can detect the vivo degradation situation of mesoporous bioglass nano-particle.Utilize
45the characteristic of Ca, can pass through tissue digestion, carry out biodistribution research in body by liquid scintillation technology to mesoporous bioglass nano-particle.
The mesoporous bioglass nano-particle of radioisotope labeling provided by the invention, effectively can carry out labelling to mesoporous bioglass nano-particle, quantitatively and intuitively can detect distribution in vivo and the accumulation situation of mesoporous bioglass nano-particle, may be used for the body absorption of bio-vitric support and chorologic research.
Be described in detail specific embodiments of the invention above, but it is just as example, the present invention is not restricted to specific embodiment described above.To those skilled in the art, any equivalent modifications that the present invention is carried out and substituting also all among category of the present invention.Therefore, equalization conversion done without departing from the spirit and scope of the invention and amendment, all should contain within the scope of the invention.
Claims (12)
1. a mesoporous bioglass nano-particle for radioisotope labeling, is characterized in that: described mesoporous bioglass nano-particle is marked with radionuclide, and described radionuclide is
31si,
32p,
45any one or a few combination in Ca.
2. the mesoporous bioglass nano-particle of radioisotope labeling according to claim 1, is characterized in that: described radionuclide is
45ca.
3. the mesoporous bioglass nano-particle of radioisotope labeling according to claim 1, is characterized in that: the composition of the mesoporous bioglass nano-particle of described radioisotope labeling comprises CaO, SiO
2and P
2o
5; Wherein, wherein, the mol ratio of Ca, Si and P is (1-30): (50-100): (1-10).
4. the mesoporous bioglass nano-particle of radioisotope labeling according to claim 1, is characterized in that: described mesoporous bioglass nanoparticle size is 50-100nm, and has meso-hole structure.
5. a preparation method for the mesoporous bioglass nano-particle of radioisotope labeling as described in as arbitrary in claim 1-4, is characterized in that, comprise the following steps:
Step a: prepare precursor sol liquid: by silicon source, calcium source, phosphorus source and surfactant dissolves in a solvent, stirs under alkali condition and joins in politef reactor after 12 hours, under 80 DEG C of conditions, carry out hydration reaction 48h; Wherein, in described calcium source, silicon source and phosphorus source, the mol ratio of Ca, Si and P is (1-30): (50-100): (1-10), wherein:
The silicon source containing radionuclide of at least trace quantity is contained in described silicon source, and/or
The calcium source containing radionuclide of at least trace quantity is contained in described calcium source, and/or
The phosphorus source containing radionuclide of at least trace quantity is contained in described phosphorus source;
Step b: the precursor liquid after step a process is sintered 5 hours at 550 DEG C of temperature, obtains the mesoporous bioglass nano-particle of described radioisotope labeling;
Step c: obtain after step b is sintered
45the mesoporous bioglass nano-particle of Ca labelling joins silane coupler dilute solution, makes its silane amination.
6. preparation method according to claim 5, is characterized in that: in step a, and described silicon source is positive silicate class; Described calcium source is inorganic calcium; Described phosphorus source is organophosphorus compounds.
7. preparation method according to claim 6, is characterized in that: described silicon source is selected from least one in ethyl orthosilicate, methyl silicate and positive silicic acid propyl ester; Described calcium source is selected from least one in lime nitrate, calcium acetate and its hydrate; Described phosphorus source is selected from least one in trimethyl phosphate and triethyl phosphate.
8. the preparation method according to claim 5,6 or 7, is characterized in that: described calcium source is calcium nitrate tetrahydrate, containing at least trace quantity
45ca (NO
3)
24H
2o.
9. preparation method according to claim 8, is characterized in that: the preparation method in described calcium source is as follows: utilize Chile saltpeter, containing trace quantity
45caCl
2calcium chloride change into containing trace quantity
45ca (NO
3)
24H
2the calcium nitrate tetrahydrate of O, then add surplus calcium nitrate tetrahydrate, both described calcium source.
10. preparation method according to claim 5, is characterized in that: in described step c, silane coupler is (3-aminopropyl) triethoxysilane.
11. preparation methoies according to claim 5, is characterized in that: in described step c, in silane coupler dilute solution, constituent proportioning is, coupling agent: ethanol=1:5V/V.
12. according to the application of mesoporous bioglass nano-particle in pharmaceutical carrier, bone filler and/or biological coating of the arbitrary described radioisotope labeling of claim 1-4.
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Cited By (2)
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|---|---|---|---|---|
| CN106316108A (en) * | 2016-08-19 | 2017-01-11 | 上海交通大学医学院附属第九人民医院 | Mesoporous bioglass nanosphere with radial pore channels and preparation method of mesoporous bioglass nanosphere with radial pore channels |
| CN110168669A (en) * | 2016-10-10 | 2019-08-23 | 肿瘤贝塔股份有限公司 | The preparation of RE-188/186 particle |
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Cited By (3)
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| CN106316108A (en) * | 2016-08-19 | 2017-01-11 | 上海交通大学医学院附属第九人民医院 | Mesoporous bioglass nanosphere with radial pore channels and preparation method of mesoporous bioglass nanosphere with radial pore channels |
| CN110168669A (en) * | 2016-10-10 | 2019-08-23 | 肿瘤贝塔股份有限公司 | The preparation of RE-188/186 particle |
| CN110168669B (en) * | 2016-10-10 | 2023-10-27 | 肿瘤贝塔股份有限公司 | Preparation of RE-188/186 particles |
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