CN1693416B - Fluorescent microball and process and application for preparing spray drying thereof - Google Patents
Fluorescent microball and process and application for preparing spray drying thereof Download PDFInfo
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- CN1693416B CN1693416B CN 200510025591 CN200510025591A CN1693416B CN 1693416 B CN1693416 B CN 1693416B CN 200510025591 CN200510025591 CN 200510025591 CN 200510025591 A CN200510025591 A CN 200510025591A CN 1693416 B CN1693416 B CN 1693416B
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Abstract
A fluorescent microsphere for treating tumor and biomedical marking is prepared from near-infrared fluorescent substance, magnetic nanoparticles, gold nanoparticles, anticancer medicine and high-molecular material through spray drying to include the first four components in the high-molecular microsphere, and linking the biologic moleculae with recognizing function to the surface of microsphere.
Description
Technical field
What the present invention relates to is a kind of fluorescent microsphere and preparation method thereof, in particular a kind of method by spray drying method for preparation magnetic near-infrared fluorescent microballoon and gold microsphere, and the fluorescent microsphere that obtains is used for belonging to nanotechnology, chemical and biomedical crossing domain in mark spike, medical diagnosis on disease and the treatment of biomedicine.
Background technology
The fluorescent mark tracer technique is a column technology of field of biology, and the material of energy emitting fluorescence also comprises the semiconductor-quantum-point nanoparticle except traditional organic fluorescent dye molecule and gold nano grain, in addition, also has rare-earth compound.They not only can be used as a kind of probe of fluorescent mark spike, can also be used for especially tumor treatment of disease.
Since the research group of the research group of Nie in 1998 and Alivisators was delivering the significant paper that quantum dot is used as the nano biological fluorescent probe in succession on " Science " since, quantum dot had caused in the world that in bio-medical applications investigators pay close attention to widely.Quantum dot is in bio-medical applications, can make people more in depth understand in the signal transduction, gene chip of mechanism of action, the cell of medicine the interaction between the protein and oncomolecularbiology mechanism etc., and can reduce the workload that people encode to Human genome.The quantum size effect of quantum dot makes the scientific research in fields such as its Clinics and Practices to disease, pharmacy, cytobiology, genomics, proteomics and molecular biology produce huge and far-reaching influence.
Near infrared fluorescence quantum point is meant the semiconductor nano crystallite at the near-infrared region emitting fluorescence, comprise the near infrared fluorescence quantum point nanoparticle of forming by single semiconductor material, with a kind of semi-conductor nano particles is nuclear, another kind of inorganic materials is the core-shell type near infrared fluorescence quantum point nano-complex particle of shell, and the nano-complex particle of near infrared fluorescence quantum point quantum well structure etc.The optical property of near infrared fluorescence quantum point is stable, the fluorescence quantum yield height.Under the exciting of near infrared light, the heat effect that near-infrared fluorescent produced of near infrared fluorescence quantum point emission is enough to the kill tumor cell.
The material that can produce near-infrared fluorescent also has the near-infrared fluorescent organic dye molecule, and it is a mark tracer material biologically commonly used, comprises rhodamine class dyestuff, the flower cyanine type dye, the sour cyanine type dye in side, thiazides and mouthful oxazines class dyestuff, phthalocyanines and complex compound dyestuff thereof, BODIPY class dyestuff etc.These near infrared organic dye have at the aspects such as early diagnosis of DNA sequencing by hybridization, immunodetection, gene recombination detection, tumour widely to be used, and the near-infrared fluorescent of these dye molecule emissions also can be used in the thermotherapy of tumour.
Gold nano grain is a fluorescent probe biologically commonly used, and golden nanometer particle itself can generate heat after absorbing near infrared light, can be used for the thermotherapy of tumour.
Tumor thermotherapy is a kind of physiatrics, and at home and abroad extremely people pay close attention to.The principle of thermotherapy method is the heat-resisting difference of utilizing between normal cell and the cancer cells, the cancer cells position is heated to about 43 ℃ and makes cancer cell death.The method of tumor thermotherapy comprises radio-frequency (RF) ablation thermotherapy between tissue, energy focusing ultrasonic-high, microwave heat therapeutic and by the whole body heating fervescence to 39.5 ℃～41.5 ℃ kept carried out thermotherapy in 2～4 hours, etc.In addition, studies show that the heat that can utilize magnetic nanoparticle to produce is come killing tumor cells under action of alternating magnetic field.
Recently, the researchists such as L.R.Hirsch of U.S. Rice University and University of Texas are adsorbed onto gold nano grain on the nano silicon particles, and the silicon that forms with 110 ± 10nm is nuclear, and the gold of 10nm thickness is the core-shell type nano composite particle of shell.They are with this nano particle injection experiments mouse tumor locus, and adopt near infrared light to excite, nano particle very fast generation heat after absorbing near infrared light as a result, within 4 to 6 minutes, tumour is just too high and deadly because of internal temperature, and the not impaired [L.R.Hirsch of health tissues around the tumour, etal.Nanoshell-mediated near-infrared thermal therapy oftumors under magnetic resonace guidance.PNAS, 2003,100 (23): 13549-13554].These studies show that nanotechnology can be used for the thermotherapy of tumour, but also thermotherapy method that may be more traditional has better superiority.
People's such as L.R.Hirsch method can make tumour cell and be organized in the very short time and be subjected to being subjected to kill and wound with regard to Yin Re, and normal cell and tissue can escape injury, this is nanotechnology and biomedical extraordinary the combination, is significant for tumor treatment.Yet the nano-complex particle of people such as L.R.Hirsch preparation does not possess the function of targeted therapy tumour.And exposed metal nanoparticle is the possibility release metal ions in vivo, to the organism toxigenicity.
Summary of the invention
At the deficiency that prior art exists, one of purpose of the present invention is to provide a kind of fluorescent microsphere;
Two of purpose of the present invention is to provide the preparation method of this fluorescent microsphere;
Three of purpose of the present invention is to provide the application of this fluorescent microsphere.
Goal of the invention of the present invention is achieved by the following technical solution:
A kind of fluorescent microsphere, form by polymer, near-infrared fluorescent material and magnetic particle or by polymer, gold nano grain and magnetic particle, a kind of in the organic molecule that described near-infrared fluorescent material is near infrared fluorescence quantum point or near-infrared fluorescent, when being near infrared fluorescence quantum point or gold nano grain, the composition of fluorescent microsphere and proportioning are: magnetic particle 0.1～40wt%, near infrared fluorescence quantum point or gold nano grain 1～50wt%, surplus is a polymer; When being the organic molecule of near-infrared fluorescent, the composition of fluorescent microsphere and proportioning are: magnetic particle 0.1～90wt%, and the organic molecule 0.01～5wt% of near-infrared fluorescent, surplus is a polymer.Above percentage ratio is weight percentage.
Can also in the mixing solutions of polymer, near-infrared fluorescent material and magnetic particle, add cancer therapy drug, perhaps in the mixing solutions of polymer, gold nano grain and magnetic particle, add cancer therapy drug.
Described microballoon is to preserve with the dried powder state, or directly is dispersed in aqueous phase that aqueous phase contains tensio-active agent, the polymer that strengthens the microballoon suspension stability, and these tensio-active agents or high molecular concentration are 0.05～5wt%; Described microballoon be shaped as sphere, elliposoidal, landing umbrella shape or other are irregularly shaped, particle diameter is 0.5～20 μ m.
Described microballoon, finishing have one or more the biomolecules in antibody, part, polypeptide, cytokine, nucleic acid or the semi-lactosi, act as absorption, chemical bonding between they and the microballoon.
Near-infrared fluorescent material of the present invention is meant near infrared fluorescence quantum point, refer in particular to elementary composition semiconductor nano crystallite at the near-infrared region emitting fluorescence by II-VI family or III-V family, comprise the near infrared fluorescence quantum point nanoparticle that single semiconductor material is formed, as InP, InAs, CdTe, HgS, HgSe, etc.; With a kind of semi-conductor nano particles is nuclear, and another kind of inorganic materials is the core-shell type near infrared fluorescence quantum point nano-complex particle of shell, as CdS/HgS, and HgS/CdS, CdTe/HgTe, CdSe/HgSe, InAs/ZnSe etc.; And the nano-complex particle of near infrared fluorescence quantum point quantum well structure such as CdSe/HgSe/CdSe, any one among the CdS/HgS/CdS etc. or several combination arbitrarily.The near infrared fluorescence quantum point granularity is 2～20nm.The near infrared fluorescence quantum point nanoparticle surface can be modified and can be strengthened particle stability or strengthen the particle wetting ability or the oil loving molecule of enhancing particle, as hydrophilic molecule, hydrophobic molecule, tensio-active agent etc.
Described near-infrared fluorescent material is meant that all can launch the organic molecule of near-infrared fluorescent under the exciting of light, comprise rhodamine class dyestuff, the flower cyanine type dye, the sour cyanine type dye in side, thiazides and mouthful oxazines class dyestuff, phthalocyanines and complex compound dyestuff thereof, BODIPY class dyestuff etc. can be launched any one or several combination arbitrarily in any class in the organic molecule of near-infrared fluorescent.
Described magnetic particle is meant martial ethiops, refers in particular to a kind of in Z 250 and the ferric oxide, and granularity is between 1nm～50nm.The magnetic particle modified surface can strengthen particle stability or strengthen the particle wetting ability or strengthen the oil loving molecule of particle, as hydrophilic molecule, hydrophobic molecule, tensio-active agent etc.
Described polymer is meant natural polymer, the combination of any one or a few in semi-synthetic polymer and the synthetic macromolecule.Described polymer refers in particular to human serum albumin, bovine serum albumin, calf casein, egg albumen, zein, starch, gelatin, gum arabic, alginates, chitosan, methylcellulose gum, ethyl cellulose, carboxymethyl cellulose, carboxylic third methylcellulose, cellulose acetate-phthalate, the d ritalinic acid Mierocrystalline cellulose, the succsinic acid cellulose acetate, polyamino acid, poly-carbon ester, polymethylmethacrylate, polyethyl methacrylate, polyacrylic resin, poly(lactic acid), the polylactic acid-polyglycol segmented copolymer, polymeric anhydride, Vicryl Rapide, 6-caprolactone rac-Lactide segmented copolymer, Sensor Chip CM 5, any one in the polystyrene or several combination arbitrarily.
Preparation method of the present invention is as follows:
The present invention obtains microballoon with the mixing solutions of polymer, near-infrared fluorescent material and magnetic particle by spray drying process, and forming with near-infrared fluorescent material and magnetic particle is core, and polymer is the composite particles of skeleton.
The present invention also obtains microballoon with the mixing solutions of polymer, gold nano grain and magnetic particle by spray drying process, and forming with gold nano grain and magnetic particle is core, and polymer is the composite particles of skeleton.
Describedly obtain microballoon by spray drying process, mixing solutions is to be atomized into drop by in pneumatic atomizer, pressure atomizer, rotary atomizer, the ultrasonic atomizer any one.The exsiccant mixing solutions concentration of waiting to spray is 0.1～60wt%, and input speed is 0.5～100mLmin
-1, inlet temperature is 10～200 ℃, air outlet temperature is regulated automatically by equipment.Carrier gas is rare gas element or air.Speed and the kind of spray-dired solution, the viscosity of solution that the present invention will fly by atomizing situation, drying temperature, the drop that changes spray-drying process wait pattern and the size-grade distribution of controlling microballoon.Spraying drying is a solvent with water or with the organic solvent, obtains sphere, elliposoidal, landing umbrella shape and other are irregularly shaped, and particle diameter is 0.5～20 μ m.
Describedly obtain microballoon, be meant that spray-dired mixing solutions is heated and makes solvent evaporates in the kiln internal cause, directly obtains water-fast microballoon by spray drying process.Or, further make the polymer (as protein) in the microballoon that sex change take place by heating by behind the spraying drying acquisition microballoon, obtain water-fast microballoon.Perhaps be meant in the exsiccant mixing solutions of waiting to spray to add glue crosslinking agent, then spraying drying.In the microballoon that obtains, embedded magnetic particle and near-infrared fluorescent material or embedded magnetic particle and gold nano grain simultaneously simultaneously.
During the preparation spray drying soln, can in the mixing solutions of polymer, near-infrared fluorescent material and magnetic particle, add cancer therapy drug, perhaps in the mixing solutions of polymer, gold nano grain and magnetic particle, add cancer therapy drug, carry out spraying drying by above-mentioned arbitrary method then.The microballoon that obtains can further be removed solvent residual in the microballoon by heat drying or lyophilize.
When described microballoon is used in biology or the human body, microballoon is sterilized, sterilization method is a kind of in heat sterilization or pressure sterilizing or Entkeimung or uv light irradiation or other aseptic techniques.
Described microballoon is used for tumor treatment.Utilize magnetic nanoparticle under the guiding in magnetic field, microballoon to be targeted to tumor locus or be fixed on tumor locus, place excitation light source at tumor locus, treat tumour under the exciting of exciting light by the heat effect that near-infrared fluorescent material or gold nano grain are produced; Or utilize the toxic action of cancer therapy drug and the heat effect of near-infrared fluorescent material or gold nano grain generation to treat tumour simultaneously.Described microballoon also is used for biomedical mark tracer study, as the imaging of immunodetection, DNA hybridization and order-checking, cell and histoorgan.
The present invention is embedded in near-infrared fluorescent material and magnetic particle in the polymer microsphere by spray drying process, and forming with near-infrared fluorescent material and magnetic particle is core, and polymer is the composite particles of skeleton.The present invention also obtains microballoon with the mixing solutions of polymer, gold nano grain and magnetic particle by spray drying process, and forming with gold nano grain and magnetic particle is core, and polymer is the composite particles of skeleton.All right further embedding cancer therapy drug in the composite particles, the surface can also connect the biomolecules with recognition function.Fluorescent microsphere provided by the invention has advantages such as magnetic target therapy, good biocompatibility, optical property be stable, can be used in the thermotherapy of mark spike in the biomedicine and tumour.In addition, the spray drying process that adopts of the present invention has the microballoon granularity and advantage such as pattern is easy to control, efficient is high, can produce in batches.In the diagnosis of biomedical mark spike, tumour and thermotherapy, have broad application prospects.
Embodiment
How further specify the present invention below in conjunction with specific embodiment realizes:
Embodiment 1:
Near infrared fluorescence quantum point CdTe, nanometer Fe with an amount of concentration
3O
4And bovine serum albumin (BSA) aqueous solution mixes, as spray-dired precursor solution.In this precursor solution, solute concentration is 30wt%.During spraying drying, input speed is 5mLmin
-1, inlet temperature is 60 ℃, 50 ± 2 ℃ of air outlet temperatures, atomizing disk rotating speed are 20000rmin
-1Carrier gas is an air.The powder that obtains continues dry down at 120 ℃, make the BSA sex change.
The result obtains the exsiccant powdered sample, and microscopic appearance is spherical, and granularity is 1～3 μ m, when BSA concentration is 1wt% in forerunner's liquid solution, acquisition be the more slick microballoon in surface of rule; When BSA concentration was 20wt% in forerunner's liquid solution, the part microsphere surface had depression and hole.All microballoons are all water insoluble, under fluorescent microscope red fluorescence arranged, and in test tube, available magnet attracts a side in test tube wall with powder.In addition, by adjusting CdTe and Fe
3O
4And the add-on of BSA, can obtain to contain the BSA microballoon of 0.1～40wt% magnetic particle, 1～50wt%CdTe easily.
Embodiment 2:
Near infrared fluorescence quantum point CdTe, nanometer Fe with an amount of concentration
3O
4And bovine serum albumin (BSA) aqueous solution mixes, as spray-dired precursor solution.In this precursor solution, solute concentration is 60wt%, and during spraying drying, input speed is 0.5mLmin
-1, inlet temperature is 60 ℃, 50 ± 2 ℃ of air outlet temperatures, atomizing disk rotary speed are 20000rmin
-1Carrier gas is an air.The powder that obtains continues dry down at 120 ℃, make the BSA sex change.
The result obtains the spheroidal particle that granularity is 5～20 μ m, its optical property, magnetic property and water-soluble etc. similar to the product of embodiment 1.
Embodiment 3:
Near infrared fluorescence quantum point CdTe, nanometer Fe with an amount of concentration
3O
4And bovine serum albumin (BSA) aqueous solution mixes, as spray-dired precursor solution.In this precursor solution, solute concentration is 0.1wt%, and during spraying drying, input speed is 100mLmin
-1, inlet temperature is 200 ℃, the atomizing disk rotary speed is 20000rmin
-1Carrier gas is an air.
The result obtains the particle that granularity mainly is distributed in 800nm～3 μ m, and individual particles only is 500nm.Most of microsphere surface has depression and hole, and microballoon is water insoluble.Its optical property, magnetic property and water-soluble etc. also similar to the product of embodiment 1.
Embodiment 4:
With gold nano grain solution and Fe
3O
4The nano particle aqueous solution and the BSA aqueous solution mix, and in the mixed solution, solute concentration is 4wt%, and wherein BSA accounts for 3wt%.Input speed is 5mLmin
-1, inlet temperature is 100 ℃, and air outlet temperature is 85 ℃, and the atomizing disk rotating speed is 20000rmin
-1Collect powder.
The result shows that the product overwhelming majority of acquisition is spherical, and granularity mainly is distributed in 3～10 μ m, and is rough.In test tube, available magnet attracts a side in test tube wall with powder.Under fluorescent microscope, red fluorescence is arranged.
Embodiment 5:
With the near infrared fluorescence quantum point CdTe solution of an amount of concentration of 20mL, the nanometer Fe of an amount of concentration of 20mL
3O
4Solution and 50mL concentration are mixed for the 0.1wt% chitosan, and adding glutaraldehyde or the formaldehyde that 1mL concentration is 0.1wt% then is linking agent, after the mixing, carries out spraying drying, and input speed is 5mLmin
-1, inlet temperature is 120 ℃, and air outlet temperature is 90 ~ 95 ℃, and the atomizing disk rotating speed is 20000rmin
-1
The result shows, acquisition be the spherical powder particle of 5～20 μ m, in test tube, also available magnet attracts a side in test tube wall with powder.Under fluorescent microscope, bright red fluorescence is arranged.
Embodiment 6:
With an amount of near infrared fluorescence quantum point CdTe powder and an amount of nanometer Fe
3O
4Powder joins in the ethanolic soln that 50mL concentration is the 1wt% ethyl cellulose and mixes, and ultrasonication 10 minutes is as spray-dired precursor solution.Input speed is 5mLmin during spraying drying
-1, inlet temperature is 10 ℃, the atomizing disk rotating speed is 20000rmin
-1To the product that obtains further at 80 ℃ of dry 1h.
The result shows, acquisition be exsiccant powder very, the product overwhelming majority is a sphere, small part is a hollow granule, granularity is 2～10 μ m.The magnetic of microballoon is similar to embodiment 1 with fluorescence.
Embodiment 7:
With the maximum emission wavelength is that 680nm silicon phthalocyanine derivative (LaJolla Blue) replaces the CdTe among the embodiment 1, presses embodiment 3 identical methods and prepares embedding LaJollaBlue and Fe simultaneously
3O
4Microballoon.
The pattern of the microballoon that the result obtains and size-grade distribution and embodiment 1 are approaching.Stronger fluorescence and magnetic are arranged.
Embodiment 8:
With an amount of Zorubicin, near infrared fluorescence quantum point CdTe powder and nanometer Fe
3O
4Powder joins in the ethanolic soln that 50mL concentration is the 1wt% ethyl cellulose and mixes, and ultrasonication 10 minutes is carried out spraying drying then, and input speed is 5mLmin
-1, inlet temperature is 50 ℃, the atomizing disk rotating speed is 20000rmin
-1The product that obtains is lyophilize 10h again, to remove residual ethanol.
The result obtains the incarnadine powder, and the granularity of product is similar to embodiment 1 to pattern, and available magnet is inhaled a side in test tube wall with powder.Under fluorescent microscope, powder particle has bright red fluorescence.
Embodiment 9:
Embedding CdTe and Fe in the time of with embodiment 1 preparation
3O
4BSA powder microballoon be raw material, they are scattered in respectively in the physiological saline that contains 0.2%Tween-80, be designated as microballoon 1; Embedding Zorubicin, CdTe and Fe in the time of in addition with embodiment 8 preparations
3O
4The ethyl cellulose microballoon be raw material, they are scattered in respectively in the physiological saline that contains 0.2%Tween-80, be designated as microballoon 2.
Get 20 of Balb/C mouse, body weight is 20 ± 2g, and is female.S180 cell on the left back shank kind of mouse, the tumour size is about 0.5～1cm behind the fortnight.Divide 5 groups at random with mouse, 4 every group.
To the 1st group of mouse: shave off the chaeta at mouse tumor position, get microballoon 1 suspension 0.3mL, carry out injecting in the knurl, above tumour, place a disc magnet, and adopt near infrared light to excite tumor locus.
To the 2nd group of mouse: shave off the chaeta at mouse tumor position, get microballoon 1 suspension 0.3mL, carry out injecting in the knurl, above tumour, place a disc magnet.
To the 3rd group of mouse: shave off the chaeta at mouse tumor position, get microballoon 2 suspension 0.3mL, carry out injecting in the knurl, above tumour, place the disc magnet that diameter is 1cm, and adopt near infrared light to excite tumor locus.
To the 4th group of mouse: shave off the chaeta at mouse tumor position, get microballoon 2 suspension 0.3mL, carry out injecting in the knurl, above tumour, place the disc magnet that diameter is 1cm.
To the 5th group of mouse: shave off the chaeta at mouse tumor position, then without any other processing.
Experiment through 7～10 found that, the 5th group of mouse of comparing, and the tumor growth of the 1st, 3,4 group of mouse obviously is suppressed, and wherein the tumour of the 3rd group of mouse is dwindled the most significantly.The growth of tumor of the 2nd group of mouse also has certain inhibition.
Embodiment 10:
Embedding CdTe and Fe in the time of with embodiment 1 preparation
3O
4BSA powder microballoon be scattered in the deionized water, mix to wherein adding an amount of semi-lactosi then, coupling is 3 hours under the room temperature.
The result has obtained the magnetic albumin fluorescent microsphere that finishing has semi-lactosi, this microballoon has initiatively and the function of passive dual-target (or location) treatment, can be used for receptor-mediated targeted therapy, also can be used as identification that fluorescent probe is used for cell and separate.
Claims (7)
1. the preparation method of a fluorescent microsphere, it is characterized in that: with water or organic solvent is solvent, obtain microballoon with the mixing solutions of polymer, near-infrared fluorescent material and magnetic particle or with the mixing solutions of polymer, gold nano grain and magnetic particle by spray drying process, formation is core with near-infrared fluorescent material or gold nano grain and magnetic particle, and polymer is the composite particles of skeleton; When being used in biology or the human body, microballoon is sterilized; Mixing solutions is atomized into drop by in pneumatic atomizer, pressure atomizer, rotary atomizer, the ultrasonic atomizer any one, and the exsiccant mixing solutions concentration of waiting to spray is 0.1～60wt%, and input speed is 0.5～100mLmin
-1, inlet temperature is 10～200 ℃, and air outlet temperature is regulated automatically by spray drying device, and carrier gas is rare gas element or air.
2. the preparation method of fluorescent microsphere according to claim 1 is characterized in that: describedly obtain microballoon by spray drying process, be meant that spray-dired mixing solutions is heated and makes solvent evaporates in the kiln internal cause, directly obtains water-fast microballoon; After perhaps mixing solutions obtains microballoon by spraying drying, further make polymer generation sex change in the microballoon, obtain water-fast microballoon by heating; Perhaps add the polymer crosslinking agent in the exsiccant mixing solutions of waiting to spray, spraying drying obtains water-fast microballoon then.
3. the fluorescent microsphere that obtains at the preparation method of claim 1 or 2, it is characterized in that: form by polymer, near-infrared fluorescent material and magnetic particle or by polymer, gold nano grain and magnetic particle, described near-infrared fluorescent material is the organic molecule of near-infrared fluorescent, when being gold nano grain, the composition of fluorescent microsphere and proportioning are: magnetic particle 0.1～40wt%, gold nano grain 1～50wt%, surplus is a polymer; When being the organic molecule of near-infrared fluorescent, the composition of fluorescent microsphere and proportioning are: magnetic particle 0.1～90wt%, organic molecule 0.01～the 5wt% of near-infrared fluorescent, surplus is a polymer, above percentage ratio is weight percentage, wherein, the organic molecule of described near-infrared fluorescent is that rhodamine class dyestuff, flower cyanine type dye, the sour cyanine type dye in side, thiazides are with any one or more than one the combination in oxazine class dyestuff, phthalocyanines and complex compound dyestuff thereof or the fluorine boron two pyroles dyestuffs.
4. a kind of fluorescent microsphere according to claim 3, it is characterized in that: in the microballoon that polymer, near-infrared fluorescent material and magnetic particle are formed, add cancer therapy drug, perhaps in the mixing solutions of polymer, gold nano grain and magnetic particle, add cancer therapy drug.
5. according to claim 3 or 4 described a kind of fluorescent microspheres, it is characterized in that: described microballoon, be to preserve with the dried powder state, or directly be dispersed in aqueous phase, aqueous phase contains the tensio-active agent that strengthens the microballoon suspension stability, and these tensio-active agents or high molecular concentration are 0.05～5wt%; Described microballoon be shaped as sphere, elliposoidal, landing umbrella shape or irregularly shaped in a kind of, particle diameter is 0.5～20 μ m.
6. according to claim 3 or 4 described a kind of fluorescent microspheres, it is characterized in that: described microballoon, finishing has one or more the biomolecules in part, polypeptide, nucleic acid or the semi-lactosi, act as absorption, chemical bonding between they and the microballoon.
7. according to claim 3 or 4 described a kind of fluorescent microspheres, it is characterized in that: described magnetic particle is a kind of in Z 250 or the ferric oxide, and granularity is between 1nm～50nm; The magnetic particle finishing can strengthen particle stability or strengthen the particle wetting ability or strengthen the oil loving molecule of particle.
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| CN101383212B (en) * | 2008-06-30 | 2011-05-25 | 上海师范大学 | Super paramagnetic/fluorescent nano particle, preparation and application thereof |
| CN101787163B (en) * | 2010-03-22 | 2011-06-08 | 天津大学 | Magnetic fluorescent microspheres and preparation method thereof |
| CN101870869B (en) * | 2010-06-29 | 2013-03-13 | 同济大学 | Preparation method of porous magnetic fluorescent nanosphere |
| CN102847493A (en) * | 2012-09-17 | 2013-01-02 | 北京科技大学 | Method for water-phase dispersion of metal magnetic nano particles |
| CN105175750B (en) * | 2015-09-10 | 2017-08-08 | 河南工业大学 | A kind of preparation method of hydrogel microsphere |
| CN110951833B (en) * | 2018-09-26 | 2022-03-29 | 中国农业大学 | Detection kit and detection method for simultaneously detecting drift or deposition of multiple spraying droplets |
| CN110951832B (en) * | 2018-09-26 | 2022-05-10 | 中国农业大学 | Kit and detection method for detecting spray droplet drifting or deposition characteristics by using magnetic nano-microspheres |
| CN111722419B (en) * | 2020-07-07 | 2021-11-02 | Tcl华星光电技术有限公司 | Nano composite particle and magnetic control display device |
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