CN105381466A - Photo-magnetic and temperature-sensitive nano-composite drug carrier and preparation method thereof - Google Patents
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Abstract
The invention provides a photo-magnetic and temperature-sensitive nano-composite drug carrier and a preparation method thereof, belongs to the field of drug carriers, and provides a preparation method to solve the problems that the prior art is relatively poor in fluorescence, magnetic property and thermosensitivity in preparation of the photo-magnetic and temperature-sensitive nano-composite drug carrier, and the preparation steps are adverse to industrial production. The method comprises the following steps: with n-isopropylacrylamide, tetraethoxysilane, ZnS:Mn<2+> quantum dots and Fe3O4 quantum dots as main raw materials, firstly, carrying out surface modification on the Fe3O4 quantum dots by oleinic acid; secondly, simultaneously embedding the ZnS:Mn<2+> quantum dots and the Fe3O4 quantum dots into SiO2; thirdly, modifying double bonds on the SiO2 surface by a silane coupling agent; and finally coating a polymer PNIPAAm through free radical polymerization, and achieving preparation of ZnS:Mn<2+> quantum dots/Fe3O4 quantum dots/SiO2/PNIPAAm of the photo-magnetic and temperature-sensitive nano-composite drug carrier.
Description
Technical field
The invention belongs to pharmaceutical carrier field, be specifically related to a kind of luminescence, magnetic, temperature sensitive complex drug carrier material and preparation method thereof.
Background technology
In Current cancer therapeutic process, ubiquitous problem is cancer therapy drug that is oral or injection is all Formulations for systemic administration, and medicine, not only to cancer cell, also can implement drug effect to healthy cell, and patients immune system is worsened further.Therefore, be badly in need of the nano combined pharmaceutical carrier of design Novel non-toxic, allow drug specificity aim at cancerous cell and not damaging adjacent healthy cell, thus improve the therapeutic efficiency to cancer, and significantly reduce the infringement to human body.
Temperature sensitive type poly compound PNIPAAm (PNIPAM) has good biocompatibility, biodegradability, and temperature switch characteristic, and preparation method is simple, good stability.In recent years, utilize PNIPAAm and there is light, the inorganic composite materials of magnetic property builds the extensive concern that nano combined pharmaceutical carrier obtains people, utilize photoluminescent property can realize its in-vivo imaging and medicine tracking, utilize magnetic orientation technology to be led by pharmaceutical carrier tumor tissues, utilize the Thermo-sensitive of polymer to realize the controllable release of medicine.Although be very promising medical carrier by PNIPAAm and inorganic nano material compound, preparation process also needs to overcome an a lot of difficult problem.A main difficult problem has two, and one is the fluorescent quenching problem of magnetic material to fluorescent material, and one is the connectivity problem of inorganic material and polymer P NIPAAm.Directly affects the magnetic of product, fluorescence and temperature sensitivity.In addition existing preparation method step is restive, and prepared complex character heterogeneity, not easily realizes industrialization.
Summary of the invention
In order to solve above-mentioned difficulties, optomagnetic temperature-sensitive nano combination drug carrier provided by the present invention, with ZnS:Mn
2+quantum dot as fluorescence source, with Fe
3o
4quantum dot, as magnetic source and with after oleic acid finishing, distinguishes coated Si O
2, re-use silane coupler to SiO
2carry out finishing, finally coated PNIPAM again, form ZnS:Mn
2+quantum dot/Fe
3o
4quantum dot/SiO
2/ PNIPAM structure.
The preparation method of described optomagnetic temperature-sensitive nano combination drug carrier is as follows:
One, by 300 ~ 600mgFe
3o
4quantum dot is scattered in 5 ~ 20ml water, adds the oleic acid of water volume 15 ~ 50%, reacts 1 ~ 6h, obtain the Fe of oleic acid modified under 20 ~ 60 DEG C of conditions
3o
4quantum dot.
Two, by the Fe after oleic acid modified
3o
4quantum dot washing, dry, pulverize after be scattered in cyclohexane extraction, obtain Fe
3o
4quantum dot ring hexane solution.
Three, by ZnS:Mn
2+quantum dot is scattered in cyclohexane extraction, obtains ZnS:Mn
2+quantum dot ring hexane solution.
Four, by polyoxyethylenes (5) nonylplenyl ether, branching (IgepalCO-520) is scattered in cyclohexane extraction, and IgepalCO-520 is 0.06 ~ 0.07:1 with the ratio of the addition of cyclohexane extraction, adds ZnS:Mn
2+the cyclohexane solution of quantum dot and Fe
3o
4quantum dot ring hexane solution, is dispersed to evenly, and add ammonia and regulate pH to alkalescence, add the ethyl orthosilicate (TEOS) of cyclohexane extraction cumulative volume 0.15% ~ 0.8%, reaction 10 ~ 40h, obtains ZnS:Mn
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano-complex, carries out washing after reaction terminates, dried; Wherein, the ZnS:Mn added
2+quantum dot ring hexane solution and Fe
3o
4znS:Mn in quantum dot ring hexane solution
2+quantum dot and Fe
3o
4the mass ratio of quantum dot is between 3:1 ~ 6:1.
Five, by ZnS:Mn
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano-complex is dispersed in the aqueous hydrochloric acid solution of pH=3 ~ 5, and 75 ~ 85 DEG C of heating 1 ~ 2h, obtain the ZnS:Mn of surface hydroxylation
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano-complex.
Six, configure the alcohol-water mixed solution (volume ratio of alcohol to water is 3 ~ 5:1) of pH=3 ~ 5.5, add silane coupler KH570, after silane coupler KH570 is hydrolyzed, add the ZnS:Mn of surface hydroxylation
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano-complex carries out finishing to it, under 70 ~ 85 DEG C of conditions, react 6 ~ 7h.Wherein the addition of silane coupler KH570 is 0.25% ~ 0.5% of alcohol-water mixed solution cumulative volume.
Seven, silane coupler is modified ZnS:Mn
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano-complex is scattered in water, add monomer NIPA (NIPAAm), acrylamide (AAm) and N-N-methylene-bisacrylamide (BIS), in removing reaction system after oxygen at 70 ~ 80 DEG C, adding the initiator for reaction time is namely obtain ZnS:Mn after 4 ~ 6h
2+quantum dot/Fe
3o
4quantum dot/SiO
2/ PNIPAAm nano-complex.Wherein, quality is than NIPA (NIPAAm): acrylamide (AAm): N,N methylene bis acrylamide (BIS): silane coupler modifies ZnS:Mn
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano-complex=4.5 ~ 5.5:0.3 ~ 0.35:0.4 ~ 0.6:1.Described initiator is potassium peroxydisulfate (KPS).
Eight, after washing, drying, pure ZnS:Mn is obtained
2+quantum dot/Fe
3o
4quantum dot/SiO
2/ PNIPAM nano-complex.
In step 6, under 70 ~ 85 DEG C of conditions, react 6 ~ 7h be two sections and carry out: first under 70 DEG C of conditions, react 5h, then temperature is brought up to 80 ~ 85 DEG C, continue reaction 1 ~ 2h and can obtain better effect.
Beneficial effect of the present invention:
1. the present invention adopts the method for reverse micro emulsion by ZnS:Mn
2+quantum dot and Fe
3o
4quantum dot is coated on SiO simultaneously
2in, prepare the silicon ball having fluorescence and magnetic concurrently.Size uniform, size is controlled, good dispersion.
2. the inventive method has carried out finishing by KH570 silane coupler to silicon ball, substantially increases the percent grafting of surface double-bond, and then significantly improves the percent grafting of polymer on silicon ball.
3. the present invention adopts traditional radical polymerization, the silica spheres with fluorescence and magnetic is just added in preparation process, one step obtains has fluorescence, magnetic and thermally sensitive polymer based nanocomposites, method is simple, favorable repeatability, can control SiO by adjustment TEOS addition
2the thickness of clad, passes through ZnS:Mn
2+quantum dot and Fe
3o
4the additional proportion adjustment of quantum dot can control the intensity of its fluorescence and magnetic.
4. the present invention is not only simple to operate, step is clear and definite, there is environmental protection, economy, convenient, simple operation and other advantages, be easy to realize large-scale production, the simultaneously polymer nanocomposites even size distribution prepared of the method, have fluorescence, magnetic and temperature sensitivity concurrently, can use as medical carrier.
5, target product of the present invention has higher fluorescence efficiency, stronger superparamagnetism and the temperature-sensitive higher than human body temperature, accommodates very much as bio-pharmaceutical carrier.
Accompanying drawing explanation
Fig. 1 target product transmission electron microscope photo of the present invention;
Fig. 2 target product light transmittance of the present invention varies with temperature curve chart;
Fig. 3 target product fluorescence emission spectrum of the present invention;
Fig. 4 a target product aqueous dispersion of the present invention photo;
Fig. 4 b target product ultraviolet excitation of the present invention photo;
Fig. 5 hysteresis curve of the present invention (in figure, M is the sample intensity of magnetization, and H is magnetic field intensity);
Under Fig. 6 external magnetic field, target product assembles photo.
Detailed description of the invention
In the mode of specific embodiment technical solution of the present invention be further explained below and illustrate.The non-specified otherwise of following examples is carried out all at normal temperatures and pressures.
In the embodiment of the present invention use reagent as follows:
Zinc acetate (Zn (CH
3cOO)
22H
2o, Shenyang Chemical Reagent Co., Ltd., Sinopharm Group, analytical pure);
Manganese acetate (Mn (CH
3cOO)
24H
2o, Aladdin reagent, analytical pure);
Oleic acid (C
18h
34o, Shenyang Chemical Reagent Co., Ltd., Sinopharm Group, analytical pure);
Enuatrol (C
18h
33naO
2, Shenyang Chemical Reagent Co., Ltd., Sinopharm Group, chemical pure);
Ethanol (C
2h
6o, Shenyang Chemical Reagent Co., Ltd., Sinopharm Group) be analytical pure;
Nine hydrated sodium sulfide (Na
2s9H
2o, Shenyang Chemical Reagent Co., Ltd., Sinopharm Group, analytical pure);
Ferric chloride (FeCl
36H
2o, Shenyang Chemical Reagent Co., Ltd., Sinopharm Group, analytical pure);
Ferrous chloride (FeCl
24H
2o, Shenyang Chemical Reagent Co., Ltd., Sinopharm Group, analytical pure);
Ammonia (NH
3h
2o, Beijing Chemical Plant, analytical pure);
Macrogol 4000 (PEG4000) (H (OGH
2cH
2)
noH, Shenyang Chemical Reagent Co., Ltd., Sinopharm Group, analytical pure);
Ethyl orthosilicate (TEOS) (C
8h
20o
4si, Shenyang Chemical Reagent Co., Ltd., Sinopharm Group, analytical pure);
Cyclohexane extraction (C
6h
12, Shenyang Chemical Reagent Co., Ltd., Sinopharm Group, analytical pure);
γ-(methacryloxypropyl) propyl trimethoxy silicane (silane coupler KH570, CH
2=C (CH
3) COOC
3h
6si (OCH
3)
3, Sigma-Aldrich, biological reagent);
NIPA (NIPAAm) (C
6h
11nO, Aladdin reagent, analytical pure);
Acrylamide (AAm) (C
3h
5nO, Aladdin reagent, top grade is pure);
Potassium peroxydisulfate (KPS) (K
2s
2o
8, Aladdin reagent, Metal Substrate (metalsbasis));
N-N-methylene-bisacrylamide (BIS) (C
7h
10n
2o
2, Aladdin reagent, electronic grade reagents);
Polyoxyethylenes (5) nonylplenyl ether, branching (IgepalCO-520) (C
2h
4o)
nc
15h
24o, n ~ 5, Aladdin reagent).
Embodiment 1
(1) solvent thermal is prepared zinc sulfide and is mixed manganese quantum dot: take 0.8561gZn (CH
3cOO)
22H
2o and 0.0097gMn (CH
3cOO)
24H
2o, is poured into and is equipped with in the 250ml beaker of 7ml deionized water, and magnetic agitation 10min is to dissolving.Then in above-mentioned solution, 9.75ml oleic acid, 1.3g enuatrol, 16ml ethanol is added successively, and magnetic agitation 1h, form latex A.By 0.937gNa
2s9H
2o pours into and is equipped with in the 250ml beaker of 7ml deionized water, and magnetic agitation 10min, to dissolving, obtains sodium sulfide solution.Sodium sulfide solution is joined in latex A, and magnetic agitation 2h obtains solution B, B solution is transferred in the reactor of 50ml, reactor is put in drying baker, and the temperature arranging drying baker is 190 DEG C, reaction 12h.The product ethanol be obtained by reacting: the solution centrifugal of cyclohexane extraction=1:1 washs three times.60 DEG C of dry 5h obtain ZnS:Mn
2+quantum dot.
(2) ferroso-ferric oxide quantum dot is prepared in co-precipitation: take 2.703gFeCl
36H
2o, 1.192gFeCl
24H
2o and 10gPEG4000 joins and fills in the 500ml three-neck flask of 150ml deionized water, and mechanical agitation is to dissolving.Solution temperature is warming up to 90 DEG C, adds 100mlNH
3h
2o, stirs 2h.Products therefrom is centrifugal, wash 3 times respectively with ethanol and deionized water.By sample dispersion in aqueous, Fe is obtained
3o
4quantum dot aqueous solution.
(3) oleic acid modified ferroso-ferric oxide quantum dot: by the Fe of preparation in 300mg step (2)
3o
4quantum dot, ultrasonic 20min is dispersed in and fills in the 100ml conical flask of 20ml deionized water, then in conical flask, adds 5ml oleic acid, is placed in shaking table after continuing ultrasonic 30min, arrange shaking table temperature 60 C, rotating speed 100rpm, and the response time is 6h.After having reacted, utilize the oleic acid that washing with alcohol three removings are unnecessary, then vacuum drying 12h at 60 DEG C, pulverizes stand-by, obtains the Fe of oleic acid modified
3o
4quantum dot.By 10mgFe
3o
4quantum dot is dispersed in 10ml cyclohexane extraction, is made into the Fe that concentration is 1mg/ml
3o
4quantum dot ring hexane solution.
(4) coated silica: measure 3.7mlIgepalCO-520, by its ultrasonic disperse in the cyclohexane extraction of 60ml, then by 2mlZnS:Mn
2+the cyclohexane solution (5mg/ml) of QDs and 2mlFe
3o
4cyclohexane solution (1mg/ml) join in above-mentioned solution simultaneously, stirring 30min makes it be uniformly dispersed, after 0.5ml ammonia (25%) is added fast, stir after 1h in system, add 250 μ lTEOS, room temperature reaction 15-20h obtains ZnS:Mn
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano composite material.End product ethanol, product for several times, then disperses preservation or 60 DEG C of dry 6h in ethanol to obtain grey-brown powder, obtains ZnS:Mn by deionized water wash
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano composite material.
(5) silane coupler finishing: take 30mgZnS:Mn
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano composite material is dispersed in the aqueous hydrochloric acid solution of 40mlPH=4, and ultrasonic 20min makes it be uniformly dispersed, and then dispersion liquid is added 85 DEG C of heating 1-2h in the three-neck flask of 250ml, obtains the ZnS:Mn of surface hydroxylation after the centrifugal 5min of 10000rpm
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano composite material.2. measure the mixed solution (ethanol: water=4:1) of 40mlPH=4, add 0.2mlKH570, be placed on magnetic stirring apparatus and stir hydrolysis 2h.Add the ZnS:Mn of surface hydroxylation
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano composite material, joins in the three-neck flask of 250ml by solution after ultrasonic disperse 30min, is placed on by three-neck flask in water-bath, at 70 DEG C, stir 5h, then water-bath temperature is brought up to 80-85 DEG C, continues to stir 1-2h.Carry out centrifugal to solution, utilize washing with alcohol 6 times, centrifugal products therefrom is dispersed in alcoholic solution to be preserved, and obtains the ZnS:Mn of KH570 surface modification
2+quantum dot/Fe
3o
4quantum dot/SiO
2alcoholic solution.
(6) surface grafting polymerization thing: the ZnS:Mn that KH570 step (5) synthesized modifies
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano composite material deionized water wash three times, and be dispersed in 100ml deionized water for ultrasonic 20min, then joined in the four neck flasks of 250ml, and be placed in water-bath, add 0.150gNIPAAm wherein, the BIS of 9.4mgAAm and 0.015g, stirs at 200 rpm with mechanical agitation rod, and logical nitrogen deoxidation 0.5h.Then water-bath is warming up to 70 DEG C, adds KPS1.5ml (4mg/ml), the response time is 4h.Centrifugal and utilize deionized water wash three times, be then placed in the dry 24h of vacuum freeze drier and obtain target product ZnS:Mn
2+quantum dot/Fe
3o
4quantum dot/SiO
2/ PNIPAAm.
Embodiment 2
Embodiment 1 is optimal way of the present invention, except embodiment 1 except the method step that describes, micromodification of the addition of raw material and reaction condition being run business into particular one becomes, with reference to existing method with according to reaction principle analysis, disclosed in summary of the invention of the present invention, reaction condition changes the material alterations that all can not cause the inventive method, all can realize the present invention.As: in the embodiment of the present invention 1 when utilizing oleic acid to modify ferroso-ferric oxide surface, add the oleic acid of deionized water volume 15% ~ 50%, 20 ~ 60 DEG C of reactions 1 ~ 6 hour during reaction.The concrete steps of coated silica can with reference to prior art, and when further hydroxylating process, under the condition of pH=3 ~ 5,75 ~ 85 DEG C of heating 1 ~ 2h can realize the hydroxylating of surface silica dioxide.When heating uses silane coupler effects on surface to modify, the addition of KH570 is 0.1 ~ 0.2mL/40mL alcohol-water solution, and needs to carry out under the condition of PH=3 ~ 5.5.The present invention is ZnS:Mn in preparation process
2+quantum dot and Fe
3o
4the mass ratio of quantum dot better can ensure the effect of magnetic and fluorescence at 3:1 ~ 6:1.Add using and being controlled to be coated with extraordinary effect for silicon dioxide between 0.06 ~ 0.07:1 of surfactant IgepalCO-520, improve technique effect of the present invention.
Embodiment 3
Structure and fuction characterizes
The present invention characterizes from 26S Proteasome Structure and Function target product respectively, characterizes with the structure of transmission electron microscope mode to target product, and as shown in Figure 1, black region is ZnS:Mn
2+quantum dot or Fe
3o
4quantum dot, its surperficial dark gray areas is surface coated SiO
2, outermost layer light gray areas is PNIPAAm.
Functional characterization of the present invention is divided into temperature-sensing property sign, magnetic characterization and the characteristics of luminescence to characterize.
The present invention varies with temperature curve by light transmittance and characterizes its temperature-sensing property.As shown in Figure 2, the phase transition temperature of target product is 41.1 DEG C, is greater than the body temperature 37 DEG C of human body, therefore can be realized the controllable release of medicine by the temperature controlling carrier.
Fig. 3 is target product ZnS:Mn of the present invention
2+quantum dot/Fe
3o
4quantum dot/SiO
2the fluorescence emission spectrum of/PNIPAAm, as can be seen from Figure 3, the glow peak of target product is positioned at 592.7nm.The target sample aqueous solution of the present invention's brown under 365nm ultraviolet excitation condition sends glassy yellow fluorescence (as shown in figures 4 a and 4b).Target product ZnS:Mn is described
2+quantum dot/Fe
3o
4quantum dot/SiO
2/ PNIPAAm can as fluorescent marker application in vivo.
Can be seen by Fig. 5, target product of the present invention has superparamagnetism.Utilize Magnet to carry out targeting experiment (as shown in Figure 6) to solution, find that target product ZnS:Mn is assembled in solution side
2+quantum dot/Fe
3o
4quantum dot/SiO
2/ PNIPAAm, solution colour becomes milky by brown, and target product ZnS:Mn is described
2+quantum dot/Fe
3o
4quantum dot/SiO
2/ PNIPAAm can realize targeting and move under the effect of external magnetic field, realizes the location release of medicine.
Claims (6)
1. an optomagnetic temperature-sensitive nano combination drug carrier, is characterized in that: have SiO at Surface coating
2znS:Mn
2+quantum dot and Surface coating have SiO
2fe
3o
4the skin of quantum dot, is coated with PNIPAM, forms nano-complex.
2. a preparation method for optomagnetic temperature-sensitive nano combination drug carrier according to claim 1, concrete steps are as follows:
One, by Fe
3o
4quantum dot is scattered in water, Fe
3o
4the mass volume ratio of quantum dot and water is 15 ~ 120mg/ml, adds the oleic acid of water volume 15% ~ 50%, reacts 1 ~ 6h, obtain the Fe of oleic acid modified under 20 ~ 60 DEG C of conditions
3o
4quantum dot;
Two, by the Fe after oleic acid modified
3o
4quantum dot washing, dry, pulverize after be scattered in cyclohexane extraction, obtain Fe
3o
4quantum dot ring hexane solution;
Three, by ZnS:Mn
2+quantum dot is scattered in cyclohexane extraction, obtains ZnS:Mn
2+quantum dot ring hexane solution;
Four, by polyoxyethylenes (5) nonylplenyl ether, branching is scattered in cyclohexane extraction, polyoxyethylenes (5) nonylplenyl ether, and the addition volume ratio of branching and cyclohexane extraction is 0.06 ~ 0.07:1, adds ZnS:Mn
2+the cyclohexane solution of quantum dot and Fe
3o
4quantum dot ring hexane solution, is dispersed to evenly, and add ammonia and regulate pH to alkalescence, add the ethyl orthosilicate of cyclohexane extraction cumulative volume 0.15% ~ 0.8%, reaction 10 ~ 40h, obtains ZnS:Mn
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano-complex, carries out washing after reaction terminates, dried; Wherein, the ZnS:Mn added
2+quantum dot ring hexane solution and Fe
3o
4znS:Mn in quantum dot ring hexane solution
2+quantum dot and Fe
3o
4the mass ratio of quantum dot is between 3:1 ~ 6:1;
Five, by ZnS:Mn
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano-complex is dispersed in the aqueous hydrochloric acid solution of pH=3 ~ 5, and 75 ~ 85 DEG C of heating 1 ~ 2h, obtain the ZnS:Mn of surface hydroxylation
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano-complex;
Six, configure the alcohol-water mixed solution of pH=3 ~ 5.5, add silane coupler KH570, after silane coupler KH570 is hydrolyzed, add the ZnS:Mn of surface hydroxylation
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano-complex carries out finishing to it, under 70 ~ 85 DEG C of conditions, react 6 ~ 7h; Wherein, the addition of silane coupler KH570 is 0.25% ~ 0.5% of alcohol-water mixed solution cumulative volume; In described alcohol-water mixed solution, the volume ratio of second alcohol and water is 3 ~ 5:1;
Seven, silane coupler is modified ZnS:Mn
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano-complex is scattered in water, adds monomer NIPA, acrylamide and N-N-methylene-bisacrylamide, in removing reaction system after oxygen at 70 ~ 80 DEG C, adding the initiator for reaction time is namely obtain ZnS:Mn after 4 ~ 6h
2+quantum dot/Fe
3o
4quantum dot/SiO
2/ PNIPAM nano-complex; Wherein, NIPA in mass ratio: acrylamide: N,N methylene bis acrylamide: silane coupler modifies ZnS:Mn
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano-complex=4.5 ~ 5.5:0.3 ~ 0.35:0.4 ~ 0.6:1.
3. the preparation method of optomagnetic temperature-sensitive nano combination drug carrier according to claim 2, is characterized in that: after washing, drying, obtain pure ZnS:Mn after step 7 completes
2+quantum dot/Fe
3o
4quantum dot/SiO
2/ PNIPAM nano-complex.
4. the preparation method of optomagnetic temperature-sensitive nano combination drug carrier according to claim 2, is characterized in that: described initiator is potassium peroxydisulfate.
5. the preparation method of optomagnetic temperature-sensitive nano combination drug carrier according to claim 2, it is characterized in that: in step 6, under 70 ~ 85 DEG C of conditions, react 6 ~ 7h be two sections and carry out: first under 70 DEG C of conditions, react 5h, then temperature is brought up to 80 ~ 85 DEG C, continue reaction 1 ~ 2h.
6. the preparation method of optomagnetic temperature-sensitive nano combination drug carrier according to claim 2, is characterized in that: NIPA in step 7: acrylamide: N,N methylene bis acrylamide: silane coupler modifies ZnS:Mn
2+quantum dot/Fe
3o
4quantum dot/SiO
2nano-complex=5:0.31:0.5:1.
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Cited By (4)
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|---|---|---|---|---|
| CN109277079A (en) * | 2018-12-01 | 2019-01-29 | 浙江海洋大学 | A kind of preparation method of the composite material of light sensitivity |
| CN109277091A (en) * | 2018-12-01 | 2019-01-29 | 浙江海洋大学 | A kind of preparation method of the composite material of Thermo-sensitive |
| CN110129025A (en) * | 2019-05-14 | 2019-08-16 | 上海大学 | The preparation method of simple Silica-coated quantum dot |
| CN115159587A (en) * | 2022-07-21 | 2022-10-11 | 江苏先丰纳米材料科技有限公司 | Preparation method of molybdenum trioxide nanosheet loaded ferroferric oxide magnetic nanoparticle |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102675565A (en) * | 2012-05-09 | 2012-09-19 | 天津大学 | Carbon quantum dot-poly N-isopropylacrylamide composite material and preparation method thereof |
| CN103204972A (en) * | 2013-04-23 | 2013-07-17 | 上海师范大学 | Thermo-sensitive fluorescent carbon nano composite material and preparation method thereof |
| CN103239410A (en) * | 2013-05-02 | 2013-08-14 | 上海交通大学 | Preparation method of fluorescence and heat/pH sensitive organic-inorganic composite microsphere carrier |
| CN103386135A (en) * | 2013-07-24 | 2013-11-13 | 上海交通大学 | Preparation method of multifunctional medicine carrier integrating magnetism, fluorescence and thermosensitivity |
-
2015
- 2015-11-18 CN CN201510793864.8A patent/CN105381466B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102675565A (en) * | 2012-05-09 | 2012-09-19 | 天津大学 | Carbon quantum dot-poly N-isopropylacrylamide composite material and preparation method thereof |
| CN103204972A (en) * | 2013-04-23 | 2013-07-17 | 上海师范大学 | Thermo-sensitive fluorescent carbon nano composite material and preparation method thereof |
| CN103239410A (en) * | 2013-05-02 | 2013-08-14 | 上海交通大学 | Preparation method of fluorescence and heat/pH sensitive organic-inorganic composite microsphere carrier |
| CN103386135A (en) * | 2013-07-24 | 2013-11-13 | 上海交通大学 | Preparation method of multifunctional medicine carrier integrating magnetism, fluorescence and thermosensitivity |
Non-Patent Citations (3)
| Title |
|---|
| GE LIU等: "Multifunctional PNIPAM/Fe3O4–ZnS hybrid hollow spheres: Synthesis, characterization, and properties", 《JOURNAL OF COLLOID AND INTERFACE SCIENCE》 * |
| JIAN CAO等: "Effects of surface modification and SiO2 thickness on the optical and superparamagnetic properties of the water-soluble ZnS:Mn2+ nanowires/Fe3O4 quantum dots/SiO2 heterostructures", 《CRYSTENGCOMM》 * |
| SUBRAMANIAN TAMIL SELVAN等: "Functional and Multifunctional Nanoparticles for Bioimaging and Biosensing", 《LANGMUIR》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109277079A (en) * | 2018-12-01 | 2019-01-29 | 浙江海洋大学 | A kind of preparation method of the composite material of light sensitivity |
| CN109277091A (en) * | 2018-12-01 | 2019-01-29 | 浙江海洋大学 | A kind of preparation method of the composite material of Thermo-sensitive |
| CN110129025A (en) * | 2019-05-14 | 2019-08-16 | 上海大学 | The preparation method of simple Silica-coated quantum dot |
| CN115159587A (en) * | 2022-07-21 | 2022-10-11 | 江苏先丰纳米材料科技有限公司 | Preparation method of molybdenum trioxide nanosheet loaded ferroferric oxide magnetic nanoparticle |
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