CN110302397A - The coating mesoporous silica drug of pH responsiveness stannic oxide/graphene nano piece is double to carry composite nanoparticle and preparation method - Google Patents
The coating mesoporous silica drug of pH responsiveness stannic oxide/graphene nano piece is double to carry composite nanoparticle and preparation method Download PDFInfo
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Abstract
The present invention relates to a kind of double load composite nanoparticles of coating mesoporous silica drug of pH responsiveness stannic oxide/graphene nano piece and preparation methods, are made of mesoporous silicon dioxide nano particle, the cinnamic acid being loaded into inside mesoporous silicon dioxide nano particle, the stannic oxide/graphene nano piece for being coated on mesoporous silicon dioxide nano particle surface and the adriamycin being loaded into stannic oxide/graphene nano chip architecture.Preparation method is to obtain after amination mesoporous silicon dioxide nano particle and stannic oxide/graphene nano piece to be passed through to physics load and the pi-conjugated loading cinnamic acid of π-and adriamycin respectively by Electrostatic Absorption.Composite nanoparticle good biocompatibility prepared by the present invention, drugloading rate is high, it releases the drug in neutral pH range less, and surface coating is quickly sloughed by the variation of stannic oxide/graphene nano piece surface charge in low ph conditions in tumour cell, realize medicine response release, it is final to improve Intracellular drug accumulation, enhancing medication effect is played, while reducing the purpose of its toxic side effect.
Description
Technical field
The invention belongs to biological medicine field of material technology, are related to a kind of pH responsiveness stannic oxide/graphene nano piece cladding Jie
Hole silica drug is double to carry composite nanoparticle and preparation method.
Background technique
Tumour is to threaten one of the major disease of human health, is mainly at present hand for the treatment method of malignant tumour
Art is aided with the means such as chemotherapy and radiotherapy and carries out complex treatment.Chemotherapy (chemotherapy) is mainly pressed down using chemicals
Tumor proliferation processed, transfer simultaneously finally kill tumour.However, often there are many defects in clinical use in most chemotherapeutics,
Such as water-soluble and stability is poor, circulation time in vivo is short and lacks targeting, not only affects the treatment, and it is secondary also to cause serious poison
Effect, to bring additional pain to patient.
Nanotechnology is research structure size material properties and a kind of emerging technology of application within the scope of Nano grade.It receives
The rice unique physicochemical properties of material make it be used widely in biomedicine field.Nanoparticle can be by dividing drug
Son is loaded into its internal build pharmaceutical carrier, and is enabled and tumor surface specificity by connecting targeting molecule on surface
The receptor of expression combines, to realize the targeting drug delivery to tumour.Ideal nano-medicament carrier should have specific target tropism, medicine
Object discharges the properties such as controllability, good biological degradability and biocompatibility.
Mesoporous silicon dioxide nano particle (mesoporous silica nanoparticles, MSN) refers to aperture between 2-
A polyporous materials of 50nm, it has ordered mesopore structure, high specific surface area, the easy modification in surface, biocompatibility
The features such as good, therefore it is widely used in field of biomedicine.The meso-hole structure of MSN allows to receive more medicines in duct
Object molecule, and the multiple types drug such as from small molecule to high molecular weight protein can be loaded by changing pore size.Drug envelope
Loaded on its loss during transportation in MSN mesopore orbit, can be reduced, thus mitigate the toxic side effect of normal tissue, and
And the cellular structure of MSN plays certain slow releasing function to drug.By adjusting MSN mesoporous pore size size, biology can be hindered
The intrusion of enzyme, to reduce the possibility that drug is degraded.The surface MSN is rich in silanol group, therefore can be by chemically reacting accordingly
Functional modification is carried out to the surface MSN, meets different drug carrier demands.
Graphene oxide (graphene oxide, GO) is a kind of two-dimensional structure carbon nanosheet, has biggish specific surface
Long-pending and good biocompatibility can be used as bio-medical material use.The unique hexagon carbocyclic ring structure of GO can be with
The pi-conjugated effect of π-occurs for the aromatic ring structure in many drug molecules, therefore can efficiently load drug.It include a large amount of carboxylics in GO structure
The water solubility of GO can be improved in base, hydroxyl and epoxy group, circulate it can in fluid environment and keeps stable.At present
Existing research show functionalization GO can efficiently load a variety of anti-tumor drugs, and the Drug controlled release under condition of different pH,
Achieve preferable therapeutic effect [Journal of Materials Chemistry, 2011,21 (10): 3448-3454].
Cinnamic acid (cinnamicaldehyde, CA) is a kind of natural aldehyde extracted from the volatile oil of traditional Chinese medicine cortex cinnamomi
Class compound contains active michael acceptor pharmacophore, and good security, is ratified as food additives to make by FDA
With.Current study show that CA can by increase cell mitochondrial in active oxygen radical (reactive oxygen species,
ROS) horizontal mode inhibits tumor proliferation, and to normal cell toxicity it is smaller [Cancer Letter, 2003,196 (2),
143-152].However the aldehyde radical in CA structure is oxidizable, so that its bioavilability is lower.Adriamycin (doxorubicin,
DOX be) current clinically widely used anti-tumor drug, anticancer spectrum is wide, can by be directly embedded into DNA core base-pair it
Between, its transcription is interfered, the formation of mRNA is prevented to play antitumor action.However DOX during clinical use there is also
Such as bone marrow suppression, cardiac toxic toxicity.Therefore, CA is loaded using the hole of MSN, utilizes the anthracene in GO and DOX structure
Ring π-πconjugation generates mutual absorption can be respectively by two kinds of Drug loadings in above two carrier, then passes through Electrostatic Absorption
The composite nanoparticle of preparation while two kinds of drugs of load, can not only reduce the degree of oxidation of CA structure, can also pass through targeting
Property raising reduce DOX toxic side effect, finally improve therapeutic effect.Therefore, which has preferable research
Value and application prospect.
Summary of the invention
Technical problems to be solved
In order to avoid the shortcomings of the prior art, the present invention proposes a kind of pH responsiveness stannic oxide/graphene nano piece cladding
Mesoporous silicon oxide drug is double to carry composite nanoparticle and preparation method, to reach raising chemotherapy effect while reduce toxic side effect
Purpose.
Technical solution
A kind of coating mesoporous silica drug of pH responsiveness stannic oxide/graphene nano piece is double to carry composite nanoparticle, spy
Sign is to include mesoporous silicon dioxide nano particle, cinnamic acid, stannic oxide/graphene nano piece and doxorubicin hydrochloride；Cinnamic acid is loaded into
Inside mesoporous silicon dioxide nano particle, stannic oxide/graphene nano piece is coated on mesoporous silicon dioxide nano particle surface, hydrochloric acid Ah mould
White, quiet clothes are loaded in stannic oxide/graphene nano chip architecture.
The lamella diameter of the stannic oxide/graphene nano piece is 100~200nm.
A kind of double systems for carrying composite nanoparticle of the coating mesoporous silica drug of pH responsiveness stannic oxide/graphene nano piece
Preparation Method, it is characterised in that steps are as follows:
Step 1, preparation load the stannic oxide/graphene nano piece of adriamycin: by stannic oxide/graphene nano piece and doxorubicin hydrochloride
It is configured to mixed aqueous solution for the ratio of 1:1~1:8 in mass ratio, 12~48h is stirred at room temperature, is obtained after washing, centrifugation, freeze-drying
Load the stannic oxide/graphene nano piece of adriamycin；The stannic oxide/graphene nano piece diameter is 100~200nm；
Step 2, preparation load the mesoporous silicon dioxide nano particle of cinnamic acid:
Prepare the mesoporous silicon dioxide nano particle of surface amination:
(1) cetyl trimethylammonium bromide, dehydrated alcohol and triethanolamine are added to the water heating to be mixed, then plus
Enter tetraethyl orthosilicate, carries out heating reaction at a temperature of 20~80 DEG C；Washed, be centrifuged repeatedly, be dried in vacuo after contained
The mesoporous silicon dioxide nano particle of template；The cetyl trimethylammonium bromide: dehydrated alcohol: triethanolamine: positive silicic acid
The molar ratio of tetra-ethyl ester are as follows: 0.14:21:1.8:2.1~1.14:21:1.8:2.1；
(2) it disperses the mesoporous silicon dioxide nano particle containing template in hydrochloric acid ethanol solution, 60~
At a temperature of 80 DEG C carry out 24~48h of heating reflux reaction, washed, be centrifuged repeatedly, be dried in vacuo after obtain template agent removing
Mesoporous silicon dioxide nano particle；The hydrochloric acid ethanol solution accounts for the 10%~15% of total solution volume, unit v/
v；The concentration of concentrated hydrochloric acid is 36~38% in the acid ethanol solution, unit w/w；
(3) mesoporous silicon dioxide nano particle of template agent removing will be gone to be added in isopropanol, adds three ethoxy of 3- aminopropyl
Base silane, at a temperature of 60~80 DEG C carry out 24~48h of heating reflux reaction, washed, be centrifuged repeatedly, be dried in vacuo after obtain
The mesoporous silicon dioxide nano particle of surface amination；The mesoporous silicon dioxide nano particle for removing template agent removing: 3- aminopropyl three
The ratio of Ethoxysilane and isopropanol is 1:20:1000~1:20:1500, unit m/v/v；
Preparation load cinnamic acid mesoporous silicon dioxide nano particle: by the mesoporous silicon dioxide nano particle of surface amination with
Cinnamic acid is configured to mixed ethanol solution according to the ratio that mass ratio is 5:1~10:1, is stirred at room temperature 12~for 24 hours, washing, from
Obtain loading the mesoporous silicon dioxide nano particle of cinnamic acid after the heart, vacuum drying；
Step 3, the double load composite nano-granules of the preparation coating mesoporous silica drug of pH responsiveness stannic oxide/graphene nano piece
Son: by concentration be 0.05~0.1g/mL loadings cinnamic acid mesoporous silicon dioxide nano particle aqueous solution and concentration be 0.05~
It after the stannic oxide/graphene nano piece aqueous solution mixing of the loading adriamycin of 0.1g/mL, is stirred at room temperature, washs, is centrifuged, vacuum is done
The double load composite nanoparticles of the coating mesoporous silica drug of pH responsiveness stannic oxide/graphene nano piece are obtained after dry；The loading
The volume ratio of the stannic oxide/graphene nano piece aqueous solution of the mesoporous silicon dioxide nano particle aqueous solution and loading adriamycin of cinnamic acid
For 1:1~1:3；The concentration of the mesoporous silicon dioxide nano particle aqueous solution for loading cinnamic acid is with mesoporous silicon dioxide nano particle
Mass Calculation；The concentration of the stannic oxide/graphene nano piece aqueous solution for loading adriamycin is with stannic oxide/graphene nano tablet quality
It calculates.
The stannic oxide/graphene nano piece: by single-layer graphene oxide according to mass volume ratio, that is, m/v be 1:1000~1:
5000 ratio prepares graphene oxide water solution, and stannic oxide/graphene nano piece is obtained after ultrasonication.
The single-layer graphene oxide with a thickness of 0.335~1nm, lamella diameter is 0.5~5 μm.
The partial size of the mesoporous silicon dioxide nano particle is 60~100nm, and Zeta potential is between 20-30mV.
A kind of coating mesoporous silica drug of pH responsiveness stannic oxide/graphene nano piece is double to carry composite nanoparticle
Application method, it is characterised in that: for medicine controlled releasing discharge field.
Beneficial effect
A kind of double loads of coating mesoporous silica drug of pH responsiveness stannic oxide/graphene nano piece proposed by the present invention are compound
Nanoparticle and preparation method, by mesoporous silicon dioxide nano particle, the cinnamic acid being loaded into inside mesoporous silicon dioxide nano particle,
It is coated on the stannic oxide/graphene nano piece on mesoporous silicon dioxide nano particle surface and is loaded into stannic oxide/graphene nano chip architecture
Adriamycin constitute.Preparation method is that amination mesoporous silicon dioxide nano particle and stannic oxide/graphene nano piece are passed through object respectively
It is obtained after reason load and the pi-conjugated loading cinnamic acid of π-and adriamycin by Electrostatic Absorption.Composite nanoparticle prepared by the present invention
Good biocompatibility, drugloading rate is high, releases the drug in neutral pH range less, and passes through oxidation in low ph conditions in tumour cell
Surface coating is quickly sloughed in the variation of graphene nanometer sheet surface charge, realizes medicine response release, is finally improved intracellular
Drug accumulation plays enhancing medication effect, while reducing the purpose of its toxic side effect.
Compared with prior art, the beneficial effects of the present invention are:
1, composite nanoparticle, good biocompatibility, small toxicity are prepared using the MSN of good biocompatibility and GO-ns.
2, GO-ns is coated on the surface MSN, can play the role of blocking MSN surface void, controls it and loads releasing for drug
It puts.
3, MSN and GO-ns only needs simple whipping process i.e. to the preparation of the loading and final composite nanoparticle of drug
It can be achieved, it is simple, convenient.
4, prepared composite nanoparticle can be shelled in acidic environment by the change responsiveness of GO-ns surface charge
From to realize the pH responsiveness release of loaded drug.
Detailed description of the invention
Fig. 1 is partial size, potentiometric detection result and the transmission electron microscope picture of MSN
Fig. 2 is MSN-NH2Partial size, potentiometric detection result and transmission electron microscope picture
Fig. 3 is MSNCATransmission electron microscope picture
Fig. 4 is the transmission electron microscope picture of GO (a) and GO-ns (b)
Fig. 5 is the partial size of GO (a) and GO-ns (b), potentiometric detection result
Fig. 6 is GODOXTransmission electron microscope picture
Fig. 7 is MSNCA@GODOXComposite nanoparticle transmission electron microscope and X-ray energy spectrum analyze result
Fig. 8 is MSNCA@GODOXComposite nanoparticle release in vitro is as a result, (a) figure is the releasing trend of CA, and (b) figure is DOX
Releasing trend
Specific embodiment
Now in conjunction with embodiment, attached drawing, the invention will be further described:
Embodiment:
1, the preparation of mesoporous silicon dioxide nano particle (MSN):
Precision weighing cetyl trimethylammonium bromide (CTAB) 2.1g is added in 100mL round-bottomed flask, adds into flask
Enter 52mL distilled water, magnetic agitation (600rpm) is to transparence solution in 60 DEG C of water-baths.It is kept stirring state, to above-mentioned mixing
Continue to be added dropwise to 12mL dehydrated alcohol and 2.8g triethanolamine in solution, continues to be slowly added to 4.7mL's dropwise after stirring 15min
Tetraethyl orthosilicate continues to stir 2h under 60 DEG C of water-baths.To which solution is cooled to room temperature after the reaction was completed, centrifugation (10,
000rpm, 5min) supernatant liquor is discarded, white solid is collected, is washed repeatedly with distilled water and dehydrated alcohol.By cleaned samples plus
Enter into the 200mL ethanol solution containing 10% concentrated hydrochloric acid (36%), flows back for 24 hours in 80 DEG C of water-baths.It is cooled to solution
It is centrifuged the MSN that (10,000rpm, 5min) collects removing template after room temperature, is washed repeatedly with distilled water and dehydrated alcohol, 60 DEG C true
Sky drying obtains MSN for 24 hours.
Another embodiment changes the additional amount of cetyl trimethylammonium bromide, mole of four substances under this technique
Than are as follows: 0.14:21:1.8:2.1；
Another embodiment changes the additional amount of cetyl trimethylammonium bromide, mole of four substances under this technique
Than are as follows: 1.14:21:1.8:2.1；
2, amination mesoporous silicon dioxide nano particle (MSN-NH2) preparation:
It weighs MSN 200mg obtained to evenly spread in 200mL isopropanol, three ethoxy of 2mL 3- aminopropyl is then added
Base silane (APTES) solution, flows back for 24 hours in 80 DEG C of water-baths.(10,000rpm, 5min) is centrifuged after solution is cooled to room temperature
Collect MSN-NH2, washed repeatedly with distilled water and dehydrated alcohol, 60 DEG C of vacuum drying obtain MSN-NH for 24 hours2。
Another embodiment changes three substance mesoporous silicon dioxide nano particles: 3- aminopropyl-triethoxy under this technique
Silane: the molar ratio of isopropanol are as follows: 1:20:1000；
Another embodiment changes three substance mesoporous silicon dioxide nano particles: 3- aminopropyl-triethoxy under this technique
Silane: the molar ratio of isopropanol are as follows: 1:20:1500, unit m/v/v；
3、MSN-NH2To the loading of cinnamic acid (cinnamaldehyde, CA)
Precision weighing 50mg CA, being added after appropriate dehydrated alcohol dissolution with 50mL volumetric flask constant volume to concentration is 1mg/mL.
Precision weighing 0.2g MSN-NH2, the CA ethanol solution 20mL of 1mg/mL is added, stirs 12h (400rpm) under room temperature, it
Faint yellow solid is collected in centrifugation (10,000rpm, 5min) afterwards, is washed repeatedly with distilled water and ethyl alcohol, and 60 DEG C of vacuum drying obtain for 24 hours
To the MSN-NH for loading CA2(MSNCA)。
Another embodiment changes the mesoporous silicon dioxide nano particle of surface amination and the matter of cinnamic acid under this technique
Amount is than being 10:1；
3, the preparation of stannic oxide/graphene nano piece (graphene oxide nanosheets, GO-ns):
The untreated GO of precision weighing 0.2g is evenly spread in 20mL distilled water, using cell crushing instrument in condition of ice bath
Lower continual ultrasonic 2h, obtains GO-ns.
4, loading of the GO-ns to doxorubicin hydrochloride (DOXHCl):
Precision weighing 10mg DOXHCl is dissolved with appropriate distilled water, is settled to concentration with 10mL brown volumetric flask and is
1mg/mL.GO-ns solution and DOXHCl are hybridly prepared into mixed solution according to GO-ns and DOXHCl mass ratio for 1:2,
(400rpm) for 24 hours is stirred at room temperature, is centrifuged (10,000rpm, 5min) later and collects precipitating, be freeze-dried after being washed with distilled water,
Obtain loading the stannic oxide/graphene nano piece (GO of adriamycinDOX)。
5, the double (MSN for carrying composite nanoparticle of the coating mesoporous silica drug of stannic oxide/graphene nano pieceCA@GODOX) system
It is standby:
Compound concentration is the GO of 0.1mg/mL respectivelyDOXAnd MSNCAAqueous solution mixes the two with the ratio of 1:2 (v/v),
12h (rpm) is stirred under room temperature, (10,000rpm, 5min) is centrifuged later and collects precipitating, is freezed after being washed with distilled water dry
It is dry, obtain MSNCA@GODOX。
Another embodiment, changes GO under this techniqueDOXAnd MSNCAThe volume ratio of aqueous solution is 1:1；Or change GODOXWith
MSNCAThe volume ratio of aqueous solution is 1:3；
MSNCA@GODOXRelease in vitro
In the present embodiment, MSN is investigated using dialysisCA@GODOXTablets in vitro behavior.Intension is simulated with pH5.0PBS
Body/lysosomal pH environment, with pH environment in pH7.4PBS simulation blood circulation.Precision weighing 10mg MSNCA@GODOXRetention is added
Molecular weight is then 2mL pH5.0PBS and pH7.4PBS to be separately added into bag in the bag filter of 3.5kDa.Bag filter is sealed
8mL is immersed in afterwards to correspond in the PBS solution of pH.It is placed in shaking table under the conditions of 100rpm, 37 DEG C and carries out release experiment, selecting
It fixes time and acquires the outer complete soln of bag filter, while supplementing isometric release liquid, ultraviolet specrophotometer and efficiently is respectively adopted
Liquid chromatograph is measured, and calculates preparation, draws cumulative release curve.
Experimental result is shown, in 48h, MSNCA@GODOXIn pH5.0PBS can quick release CA and DOX, and accumulate
Release rate is higher (89% and 81%), and in pH7.4PBS, MSNCA@GODOXOnly release 66% CA and 24% DOX.Knot
Fruit shows MSNCA@GODOXChanged in low ph conditions in tumour cell in lysosome/endosome by GO surface charge so that
Electrostatic attraction weakens, and so as to be rapidly separated GO, and accelerates the release of CA.Protonation of the DOX in acidic environment simultaneously makes it
It can be detached from the pi-conjugated effect of π-of GO, therefore also accelerate the release of DOX.This release characteristics can effectively improve drug in tumour
Intracellular accumulation, and toxicity caused by reducing it due to the release in advance in blood circulation, finally improve therapeutic effect.
Claims (7)
1. a kind of coating mesoporous silica drug of pH responsiveness stannic oxide/graphene nano piece is double to carry composite nanoparticle, feature
It is to include mesoporous silicon dioxide nano particle, cinnamic acid, stannic oxide/graphene nano piece and doxorubicin hydrochloride；Cinnamic acid is loaded into Jie
Inside the silica dioxide nano particle of hole, stannic oxide/graphene nano piece is coated on mesoporous silicon dioxide nano particle surface, doxorubicin hydrochloride
It is loaded into stannic oxide/graphene nano chip architecture.
2. the coating mesoporous silica drug of pH responsiveness stannic oxide/graphene nano piece is double according to claim 1 carries compound receive
Rice corpuscles, it is characterised in that: the lamella diameter of the stannic oxide/graphene nano piece is 100~200nm.
3. the coating mesoporous silica drug of pH responsiveness stannic oxide/graphene nano piece described in a kind of claim 1 is double to carry compound receive
The preparation method of rice corpuscles, it is characterised in that steps are as follows:
Step 1, preparation load the stannic oxide/graphene nano piece of adriamycin: stannic oxide/graphene nano piece and doxorubicin hydrochloride are pressed matter
Amount is stirred at room temperature 12~48h, is loaded after washing, centrifugation, freeze-drying than being that the ratio of 1:1~1:8 is configured to mixed aqueous solution
The stannic oxide/graphene nano piece of adriamycin；The stannic oxide/graphene nano piece diameter is 100~200nm；
Step 2, preparation load the mesoporous silicon dioxide nano particle of cinnamic acid:
Prepare the mesoporous silicon dioxide nano particle of surface amination:
(1) cetyl trimethylammonium bromide, dehydrated alcohol and triethanolamine are added to the water heating to be mixed, are added just
Tetraethyl orthosilicate carries out heating reaction at a temperature of 20~80 DEG C；Washed, be centrifuged repeatedly, be dried in vacuo after obtain containing template
The mesoporous silicon dioxide nano particle of agent；The cetyl trimethylammonium bromide: dehydrated alcohol: triethanolamine: positive silicic acid tetrem
The molar ratio of ester are as follows: 0.14:21:1.8:2.1~1.14:21:1.8:2.1；
(2) it disperses the mesoporous silicon dioxide nano particle containing template in hydrochloric acid ethanol solution, at 60~80 DEG C
At a temperature of carry out 24~48h of heating reflux reaction, washed, be centrifuged repeatedly, be dried in vacuo after obtain the mesoporous of template agent removing
Silica dioxide nano particle；The hydrochloric acid ethanol solution accounts for the 10%~15% of total solution volume, unit v/v；Institute
The concentration for stating concentrated hydrochloric acid in acid ethanol solution is 36~38%, unit w/w；
(3) mesoporous silicon dioxide nano particle of template agent removing will be gone to be added in isopropanol, adds 3- aminopropyl-triethoxy silicon
Alkane, at a temperature of 60~80 DEG C carry out 24~48h of heating reflux reaction, washed, be centrifuged repeatedly, be dried in vacuo after obtain surface
Amidized mesoporous silicon dioxide nano particle；The mesoporous silicon dioxide nano particle for removing template agent removing: three ethoxy of 3- aminopropyl
The ratio of base silane and isopropanol is 1:20:1000~1:20:1500, unit m/v/v；
Preparation loads the mesoporous silicon dioxide nano particle of cinnamic acid: by the mesoporous silicon dioxide nano particle of surface amination and cortex cinnamomi
Aldehyde is configured to mixed ethanol solution according to the ratio that mass ratio is 5:1~10:1, is stirred at room temperature 12~for 24 hours, washing, centrifugation, true
Obtain loading the mesoporous silicon dioxide nano particle of cinnamic acid after sky is dry；
Step 3, the double load composite nanoparticles of the preparation coating mesoporous silica drug of pH responsiveness stannic oxide/graphene nano piece: will
The mesoporous silicon dioxide nano particle aqueous solution and concentration for the loading cinnamic acid that concentration is 0.05~0.1g/mL are 0.05~0.1g/
After the stannic oxide/graphene nano piece aqueous solution mixing of the loading adriamycin of mL, it is stirred at room temperature, after washing, be centrifuged, being dried in vacuo
Obtain the double load composite nanoparticles of the coating mesoporous silica drug of pH responsiveness stannic oxide/graphene nano piece；The loading cortex cinnamomi
The mesoporous silicon dioxide nano particle aqueous solution of aldehyde and the volume ratio for loading the stannic oxide/graphene nano piece aqueous solution of adriamycin are 1:1
~1:3；The concentration of the mesoporous silicon dioxide nano particle aqueous solution for loading cinnamic acid is with the matter of mesoporous silicon dioxide nano particle
Amount calculates；The concentration of the stannic oxide/graphene nano piece aqueous solution for loading adriamycin is in terms of stannic oxide/graphene nano tablet quality
It calculates.
4. according to the method described in claim 3, it is characterized by: the stannic oxide/graphene nano piece: by mono-layer graphite oxide
Alkene prepares graphene oxide water solution according to the ratio that mass volume ratio, that is, m/v is 1:1000~1:5000, after ultrasonication
Obtain stannic oxide/graphene nano piece.
5. according to the method described in claim 3, it is characterized by: the single-layer graphene oxide with a thickness of 0.335~
1nm, lamella diameter are 0.5~5 μm.
6. according to the method described in claim 3, it is characterized by: the partial size of the mesoporous silicon dioxide nano particle be 60~
100nm, Zeta potential is between 20-30mV.
7. the coating mesoporous silica drug of pH responsiveness stannic oxide/graphene nano piece described in a kind of claim 1 is double to carry compound receive
The application method of rice corpuscles, it is characterised in that: discharge field for medicine controlled releasing.
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