CN106916266A - A kind of preparation and its application of quadruple responsive nano compound - Google Patents
A kind of preparation and its application of quadruple responsive nano compound Download PDFInfo
- Publication number
- CN106916266A CN106916266A CN201710092318.0A CN201710092318A CN106916266A CN 106916266 A CN106916266 A CN 106916266A CN 201710092318 A CN201710092318 A CN 201710092318A CN 106916266 A CN106916266 A CN 106916266A
- Authority
- CN
- China
- Prior art keywords
- quadruple
- nano
- hours
- milliliters
- complex
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F292/00—Macromolecular compounds obtained by polymerising monomers on to inorganic materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Materials Engineering (AREA)
- Polymers & Plastics (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Carbon And Carbon Compounds (AREA)
Abstract
The present invention relates to a kind of quadruple responsive nano compound, the nano-complex is using the disulfide bond of reduction fracture as tie point, by atom transition free radical polymerization reaction in redox graphene mesoporous silicon oxide composite surface polymerized methacrylic acid dimethylaminoethyl.Nano-complex of the invention not only has temperature, pH and reduction response, is also responded near infrared light, can be had a wide range of applications in control release field.
Description
Technical field
The invention belongs to technical field of polymer materials, relate to a kind of near infrared light, temperature, pH and reduction quadruple sound
The preparation and its application of answering property nano-complex.
Background technology
In recent years, various nano-carriers achieve significant progress for control release, especially mesoporous dioxy
SiClx.With the release that mesoporous silicon oxide is used for guest molecule as carrier there is good biocompatibility, surface to be easy to modify, load
The advantages of measuring big, but simple Metaporous silicon dioxide material cannot meet the controllability requirement of guest molecule release, Yi Jicun
Loading the problem that guest molecule is revealed in advance.
In addition, most of nano-carrier currently used for control release is all single response, such as to pH, temperature, light is reduced
The sensitivities such as agent, and environment complicated and changeable is faced, the nano-carrier of single stimuli responsive cannot meet reality need, limit
Its application has been made, and the nano-carrier of multiple stimulation response can more preferably, more play the effect of control release.
The nano-complex of stimulating responsive has application well in the control release field of medicine.Due in organism
Complex environment, the nano-carrier of pH stimuli responsives has been obtained for being extensively studied.Disulfide bond is a Protein requirement three
The important covalent bond of dimension network, can degrade, typically in the presence of reducing agent (glutathione or dithiothreitol (DTT))
In the case of cancer cell show reproducibility, so obtaining numerous studies as bonding agent with disulfide bond.Comparatively, near infrared light
It is fewer that the nano-carrier of response is reported, because it is spatiotemporal well, biocompatibility is such that it is able to more accurately realize medicine
Thing control release.
The content of the invention
In order to solve the above problems, the invention provides a kind of quadruple near infrared light, temperature, pH and reduction response
The preparation method and application of the nano-complex of response.
In order to solve the above technical problems, the technical solution adopted by the present invention is as follows：
A kind of quadruple responsive nano compound, the nano-complex is using the disulfide bond of reduction fracture as connection
Point, by atom transition free radical polymerization reaction in redox graphene-mesoporous silicon oxide composite surface polymeric MAO
Dimethylaminoethyl acrylate.
The optimal technical scheme of quadruple responsive nano compound is that the nano-complex is with redox graphene
Inlay and the nano-carrier rGO@mSiO with sandwich structure are formed into mesoporous silicon oxide2, with double two sulphur of reduction fracture
Ether as the bonding agent between rGO@mSiO2 and temperature, pH sensitive polymethylacrylic acid dimethylaminoethyl (PDMAEMA),
Obtain the polymer wrapped rGO@mSiO with quadruple response2Nano-complex.
The optimal technical scheme of quadruple responsive nano compound is, the polymer wrapped rGO@of the quadruple response
mSiO2Nano-complex there is following structural formula：
The optimal technical scheme of quadruple responsive nano compound is, the redox graphene-mesoporous silicon oxide
Compound is that graphene oxide is reduced in buck, with cetyl trimethylammonium bromide as template, by tetraethyl orthosilicate
Hydrolyze to form graphite alkene-meso-porous titanium dioxide silicon compound.
The invention further relates to the preparation method of this quadruple responsive nano compound, comprise the following steps that：
1) redox graphene-meso-porous titanium dioxide silicon compound is prepared：By 40~60 milligrams of graphene oxides 500~
2~3h of ultrasound is smashed in the ultrasonic machine of 700W power；Broken graphene oxide is dispersed in the buck of pH=11~12,
75~85 DEG C of oil bath stirring 12h are reduced, and are subsequently adding 1.5~2.0 grams of cetyl trimethylammonium bromide and are adjusted pH
=11.8~12 stirrings 30 minutes, are eventually adding 850~900 microlitres of tetraethyl orthosilicates and continue to stir 24h in 75~85 DEG C of oil baths,
Redox graphene-meso-porous titanium dioxide silicon compound is obtained after centrifugation；
2) compound is surface-functionalized：By step 1) 230~270 milligrams of compounds obtaining are distributed in toluene,
Stirred under 75~85 DEG C of oil baths 30 minutes, 2~3 milliliters of isocyanatopropyl triethoxysilanes are then added dropwise and flow back 24 hours, from
The heart, cleaning, vacuum drying；The product that will be obtained is distributed in 25~30 milliliters of DMFs, and double (2- are then added dropwise
Hydroxyethyl) disulfide, oil bath is stirred 24~36 hours at 75~85 DEG C, centrifugation, cleaning, vacuum drying；By above-mentioned product
It is re-dispersed into 20 milliliters of anhydrous tetrahydro furans, ice bath, when temperature is cooled to 0 DEG C, adds 0.8~0.9 milliliter of three second
Amine and the bromo- 2- methyl propionyl bromides of 2-, after 0 DEG C is reacted 2~3 hours, are then transferred to react 24~36 hours, wherein isocyanide at room temperature
The mol ratio of sour propyl-triethoxysilicane, double (2- hydroxyethyls) disulfides and the bromo- 2- methyl propionyl bromides of 2- is 1:1:1~2；
3) removing template is removed：The product that step 2 is obtained is re-dispersed into the ethanol solution of 0.6wt% ammonium nitrate, 70~
80 DEG C flow back 2~3 hours, repeat this step 3 time be centrifuged afterwards, clean, be vacuum dried after it is standby；
4) by step 3) surface-functionalized 230~270 milligram redox graphene-mesoporous silicon oxide for obtaining is multiple
Compound, 6~6.8 milliliters of dimethylaminoethyl methacrylates and 25~28 milligrams of cuprous bromides, are distributed to dry 12 milliliters
In DMF, it is placed in Schlenk flask, with syringe by 52~57 microlitre of three (2- dimethylaminoethyls) amine
It is expelled in Schlenk flask, 48 is reacted in temperature is 75~85 DEG C of oil baths after " freezing-pumping-thaw " five to eight circulations
~60 hours, after being then centrifuged for, clean, being vacuum dried, obtain triple responsive nano compounds, wherein cuprous bromide, three (2-
Dimethylaminoethyl) mol ratio of amine and dimethylaminoethyl methacrylate is 1:1:175~200.
The optimal technical scheme of the nano-complex preparation method is, the step 1) in, the preparation of graphene oxide
Method is improved Hummer ' s methods：Sodium chloride of 1 gram of the natural graphite flakes with 60 grams grinds in being blended in grinding body, then with 1~2
Rise water and mix suction filtration after sodium dissolving to be chlorinated, the graphite that will be obtained is in 80~90 DEG C of dried in vacuum overnight；Dry graphite flake with
Stirred 8~12 hours under the H2SO2 mixed room temperatures of the 98% of 23 milliliters, 3 grams of potassium permanganate be slowly added under condition of ice bath,
Stirred 30 minutes in 38~42 DEG C of oil baths again, be heated to 70~80 DEG C and be incubated 45 minutes, be subsequently adding 3 milliliters of deionization
Water, 3 ml deionized waters are added after being heated to 100~105 DEG C of insulations 5 minutes, insulation added after 5 minutes 40 milliliters go from
Sub- water, maintains temperature at 100~105 DEG C, adds 140 ml deionized waters and 10 milliliter 30% of H2O2 to terminate anti-after 15 minutes
Should.Graphene oxide is obtained after centrifugation.
The invention further relates to the application of this quadruple responsive nano compound, nano-complex is dispersed in deionized water
In, concentration is 3~6mg/ml, while 50 milligrams of water miscible guest molecules are added, it is to be installed with magnetic stirrer 24 hours
After load process terminates, carry out what the dialysis most of unloaded of removal in 48~60 hours was entered with the bag filter of molecular cut off 3500
Guest molecule, is then repeatedly centrifuged untill the supernatant being centrifuged out does not have fluorescence, and freeze-drying obtains loading guest molecule
The nano-complex of son.
The optimal technical scheme of the quadruple responsive nano compound application is that the guest molecule is rhodamine B.
The optimal technical scheme of the quadruple responsive nano compound application is, the guest molecule near infrared light,
Temperature, pH and reduction quadruple response release are controllable.
The optimal technical scheme of the quadruple responsive nano compound application is, the controllable guest molecule of the insoluble drug release
Reducing agent dithiothreitol is added in son, the small molecule of loading is discharged from nano-complex.
The optimal technical scheme of the quadruple responsive nano compound application is that the controllable guest molecule of insoluble drug release exists
Under near infrared light, the heat energy that the graphene oxide of reduction is produced makes the polymer shrink of temperature-responsive open duct, object
Molecule discharges.
The preparation method of the nano-complex of above-mentioned quadruple response, its specific syntheti c route is as follows：
1)rGO@mSiO2Nano-carrier preparation
2) polymer rGO@mSiO2Surface-functionalized and polymer grafting
The present invention enters in mesoporous silicon oxide the redox graphene " inlaying " near infrared light fuel factor to be formed
Nano-carrier (rGO@mSiO with sandwich structure2), then using double (2- hydroxyethyls) disulfides of reduction fracture as
rGO@mSiO2And the bonding agent between the polymethylacrylic acid dimethylaminoethyl (PDMAEMA) responded with temperature, pH, obtain
To the polymer wrapped rGO@mSiO responded with quadruple2Nano-complex, after this nano-complex loads guest molecule
Can be used for control release.
The present invention is advantageous in that：The nano-complex that the present invention is prepared have near infrared light, temperature, pH and
Reduction quadruple stimuli responsive.Under near infrared light, the heat energy that the graphene oxide of reduction is produced makes the polymerization of temperature-responsive
Thing shrinks opens duct, while heat accelerates the guest molecule release that molecular diffusion rates promote to load.It is same by external heat
The polymer shrink of temperature-responsive can be made to open duct, promote the guest molecule for loading to release while heat accelerates molecular diffusion rates
Put.Under conditions of acidity, polymer proton positively charged is covered in electronegative redox graphene-mesoporous silicon oxide
Compound inhibits the release of guest molecule；Conversely, under alkalescence condition, polymer and the mesoporous silicon oxide point of deprotonation
From promoting release；The addition of reducing agent causes disulfide bonds, and the polymer P DMAEMA opening ducts that come off promote loading
Guest molecule release.The present invention has in fields such as drug controlled releases and widely applies.
Brief description of the drawings
Fig. 1 is the rGO@mSiO for preparing2Transmission electron microscope shape appearance figure；
Fig. 2 is the rGO@mSiO for preparing2Nitrogen adsorption with desorption accompanying drawing and mesoporous pore size size distribution figure；
Fig. 3 is the x-ray photoelectron energy spectrum diagram of the nano-complex for preparing；
Fig. 4 is the infrared spectrogram of nano-complex, and a is that GO, b are rGO@mSiO2, c be rGO@mSiO2- SS-Br, d are
rGO@mSiO2-SS-P；
Fig. 5 is the thermogravimetic analysis (TGA) figure of nano-complex, and a is rGO@mSiO2, b be rGO@mSiO2-SS-P；
Fig. 6 is graphite oxide olefinic base material (the 0.5mg ml for preparing-1) near infrared light (3W cm2) induction temperature become
Change figure；
Fig. 7 is bent to be loaded in burst size of the rhodamine B in nano-complex under the stimulation of pH or temperature in embodiment 1
Line；
Fig. 8 is released for the rhodamine B being loaded in nano-complex in embodiment 1 under the stimulation of the reducing agent of various concentrations
High-volume curve；
Fig. 9 is rhodamine B near infrared light (the 3W cm being loaded in embodiment 1 in nano-complex2) in special time
Point shines the burst size curve of 10 minutes；
Figure 10 be embodiment 1 in be loaded in the rhodamine B in nano-complex quadruple stimulate synergy under release
Amount curve.
Specific embodiment
Embodiment 1
A kind of preparation method of quadruple responsive nano compound is as follows：
Step 1. prepares redox graphene-meso-porous titanium dioxide silicon compound：Prepared using improved Hummer ' s methods
Graphene oxide：Sodium chloride of 1 gram of the natural graphite flakes with 60 grams grinds in being blended in grinding body, then mixes with 1~2 liter of water and treat chlorine
Change suction filtration after sodium dissolving, the graphite that will be obtained is in 80~90 DEG C of dried in vacuum overnight；Dry graphite flake and the 98% of 23 milliliters
H2SO2 mixed room temperatures under stir 8~12 hours, 3 grams of potassium permanganate is slowly added under condition of ice bath, then at 38~42 DEG C
Stirred 30 minutes in oil bath, be heated to 70~80 DEG C and be incubated 45 minutes, be subsequently adding 3 milliliters of deionized water, be heated to 100
~105 DEG C of insulations add 3 ml deionized waters after 5 minutes, and insulation adds 40 milliliters of deionized water after 5 minutes, maintain temperature
At 100~105 DEG C, 140 ml deionized waters and 10 milliliter 30% of H are added after 15 minutes2O2Terminating reaction.Obtained after centrifugation
Graphene oxide；The graphene oxide that will be obtained ultrasound 3h in the ultrasonic machine of 500W power is smashed；50mg is crushed
Graphene oxide is dispersed in 90 milliliters of bucks of pH=12, and 80 DEG C of oil bath stirring 12h are reduced, and are subsequently adding 1.8 grams
Cetyl trimethylammonium bromide simultaneously adjusts pH=12 stirrings 30 minutes, is eventually adding 900 microlitres 80 DEG C of oil of tetraethyl orthosilicate
Bath continues to stir 24 hours, and redox graphene-meso-porous titanium dioxide silicon compound is obtained after centrifugation；
Step 2. redox graphene-meso-porous titanium dioxide silicon compound it is surface-functionalized：250 that step 1 is obtained
The compound of milligram is distributed to and is stirred under 80 DEG C of oil baths in 50 milliliters of toluene 30 minutes, and 2.5 milliliters of isocyanic acid is then added dropwise
Propyl-triethoxysilicane flows back 24 hours, centrifugation, cleaning, vacuum drying；Then in order to introduce the disulfide bond that reduction is responded, will
The product for obtaining is distributed in 30 milliliters of DMF, and 3 milliliters double (2- hydroxyethyls) two sulphur are then added dropwise
Oil bath is stirred 24 hours at 80 DEG C of ether, centrifugation, cleaning, vacuum drying；It is finally introducing drawing for atom transition free radical polymerization reaction
Hair agent, ice bath in 20 milliliters of anhydrous tetrahydro furan is re-dispersed into by product, when temperature is cooled to 0 DEG C, adds 0.85 milli
After the bromo- 2- methyl propionyl bromide of triethylamine and 2.5 milliliters of 2- for rising, 0 DEG C of reaction 2 hours, it is then transferred to react 24 at room temperature small
When；
Step 3. removes removing template：The product that step 2 is obtained is re-dispersed into the ethanol solution of 0.6wt% ammonium nitrate,
70 DEG C flow back 3 hours, repeat this step 3 time be centrifuged afterwards, clean, be vacuum dried after it is standby；
Surface-functionalized redox graphene-meso-porous titanium dioxide silicon compound (250 that step 4. obtains step 3
Milligram), dimethylaminoethyl methacrylate (6 milliliters) and cuprous bromide (28 milligrams) be dispersed in 12 milliliters of N, N- dimethyl
In formamide, it is placed in Schlenk flask, 55 microlitres three (2- dimethylaminoethyls) amine is expelled to Schlenk with syringe
In flask, temperature is to react 48 hours in 75 DEG C of oil baths again after " freezing-pumping-thaw " five to eight circulations, is then centrifuged for, clearly
Wash, be vacuum dried after obtain quadruple responsive nano compound.
The loading process of guest molecule rhodamine B：By nano-complex dispersion in deionized water, concentration is 5mg/ml,
50 milligrams of water miscible rhodamine Bs are added simultaneously, with magnetic stirrer 24 hours, after loading process terminates, with retention
The bag filter of molecular weight 3500 carries out the guest molecule that the dialysis most of unloaded of removal in 60 hours is entered, and then repeatedly centrifugation is straight
To the supernatant being centrifuged out does not have fluorescence, freeze-drying obtains loading the nano-complex of guest molecule.
The nano-complex control release process of above-mentioned loading guest molecule is：The release operation of pH responses is, by 2 milligrams
The nano-complex of above-mentioned loading rhodamine B be distributed in 2 milliliters of the cushioning liquid of different pH value, then put into retention point
It is placed in the cushioning liquid small beaker equipped with 30 milliliters of corresponding pH value in the sub bag filter measured as 3500, per at regular intervals
Take out 2 milliliters and add 2 milliliters of fresh cushioning liquid, determine the ultra-violet absorption spectrum of taking-up solution to determine the tired of rhodamine
Meter burst size.The release operation for reducing response is similar with the release operation that pH is responded, the difference is that reducing agent is added into buffering
In solution；The release operation of temperature-responsive is similar with the release operation that pH is responded, the difference is that small beaker is placed on different
It is incubated in temperature.The release operation of near infrared light response is also similar to, but the concentration for loading the nano-complex of guest molecule is
0.5 mg/ml, and liquid in taking out bag filter at the 4th hour and the 9th hour during the release shines near infrared light
Penetrate to put back to again within 10 minutes in bag filter and continue to discharge.
Embodiment 2
Step 1. prepares redox graphene-meso-porous titanium dioxide silicon compound：Prepared using improved Hummer ' s methods
Graphene oxide, the graphene oxide that will be obtained ultrasound 2h in the ultrasonic machine of 600W power is smashed；60mg is crushed
Graphene oxide is dispersed in 100 milliliters of bucks of pH=11, and 85 DEG C of oil bath stirring 12h are reduced, and are subsequently adding 2.0 grams
Cetyl trimethylammonium bromide simultaneously adjusts pH=11.8 stirrings 30 minutes, is eventually adding 850 microlitres of 85 DEG C of tetraethyl orthosilicate
Oil bath continues to stir 24 hours, and redox graphene-meso-porous titanium dioxide silicon compound is obtained after centrifugation.
Step 2. redox graphene-meso-porous titanium dioxide silicon compound it is surface-functionalized：270 that step 1 is obtained
The compound of milligram is distributed to and is stirred under 85 DEG C of oil baths in 50 milliliters of toluene 30 minutes, and 3.0 milliliters of isocyanic acid is then added dropwise
Propyl-triethoxysilicane flows back 24 hours, centrifugation, cleaning, vacuum drying；Then in order to introduce the disulfide bond that reduction is responded, will
The product for obtaining is distributed in 25 milliliters of DMF, and 3 milliliters double (2- hydroxyethyls) two sulphur are then added dropwise
Oil bath is stirred 24 hours at 85 DEG C of ether, centrifugation, cleaning, vacuum drying；It is finally introducing drawing for atom transition free radical polymerization reaction
Hair agent, ice bath in 20 milliliters of anhydrous tetrahydro furan is re-dispersed into by product, when temperature is cooled to 0 DEG C, adds 0.9 milliliter
Triethylamine and the bromo- 2- methyl propionyl bromides of 2.5 milliliters of 2-, 0 DEG C reaction 2 hours after, be then transferred to react at room temperature 24 hours；
Step 3. removes removing template：The product that step 2 is obtained is re-dispersed into the ethanol solution of 0.6% (wt) ammonium nitrate
In, 80 DEG C flow back 3 hours, repeat this step 3 time be centrifuged afterwards, clean, be vacuum dried after it is standby；
Surface-functionalized redox graphene-meso-porous titanium dioxide silicon compound (270 that step 4. obtains step 3
Milligram), dimethylaminoethyl methacrylate (6.8 milliliters) and cuprous bromide (25 milligrams) be dispersed in 12 milliliters of N, N- diformazans
In base formamide, it is placed in Schlenk flask, 57 microlitres three (2- dimethylaminoethyls) amine is expelled to Shu Lun with syringe
In gram flask, temperature is to react 60 hours in 85 DEG C of oil baths again after " freezing-pumping-thaw " five to eight circulations, be then centrifuged for,
Cleaning, vacuum drying obtain quadruple responsive nano compound.
The loading process of guest molecule rhodamine B：By nano-complex dispersion in deionized water, concentration is 5mg/ml,
50 milligrams of water miscible rhodamine Bs are added simultaneously, with magnetic stirrer 24 hours, after loading process terminates, with retention
The bag filter of molecular weight 3500 carries out the guest molecule that the dialysis most of unloaded of removal in 48 hours is entered, and then repeatedly centrifugation is straight
To the supernatant being centrifuged out does not have fluorescence, freeze-drying obtains the controllable guest molecule of insoluble drug release.
The nano-complex control release process of above-mentioned loading guest molecule is：The release operation of pH responses is, by 2 milligrams
The nano-complex of above-mentioned loading rhodamine B be distributed in 2 milliliters of the cushioning liquid of different pH value, then put into retention point
It is placed in the cushioning liquid small beaker equipped with 30 milliliters of corresponding pH value in the sub bag filter measured as 3500, per at regular intervals
Take out 2 milliliters and add 2 milliliters of fresh cushioning liquid, determine the ultra-violet absorption spectrum of taking-up solution to determine the tired of rhodamine
Meter burst size.The release operation for reducing response is similar with the release operation that pH is responded, the difference is that reducing agent is added into buffering
In solution；The release operation of temperature-responsive is similar with the release operation that pH is responded, the difference is that small beaker is placed on different
It is incubated in temperature.The release operation of near infrared light response is also similar to, but the concentration for loading the nano-complex of guest molecule is
0.5 mg/ml, and liquid in taking out bag filter at the 4th hour and the 9th hour during the release shines near infrared light
Penetrate to put back to again within 10 minutes in bag filter and continue to discharge.
Claims (10)
1. a kind of quadruple responsive nano compound, it is characterised in that the nano-complex is with the disulfide bond of reduction fracture
As tie point, by atom transition free radical polymerization reaction in redox graphene-mesoporous silicon oxide composite surface
Polymerized methacrylic acid dimethylaminoethyl.
2. a kind of quadruple responsive nano compound according to claim 1, it is characterised in that the nano-complex be with
Redox graphene is inlayed and the nano-carrier rGO@mSiO2 with sandwich structure is formed into mesoporous silicon oxide, with also
Double disulfides of original fracture are obtained as the bonding agent between rGO@mSiO2 and polymethylacrylic acid dimethylaminoethyl PDMAEMA
To the nano-complex of the polymer wrapped rGO@mSiO2 responded with quadruple.
3. a kind of quadruple responsive nano compound according to claim 1, it is characterised in that the polymerization of the quadruple response
The nano-complex of thing parcel rGO@mSiO2 has following structural formula：
4. a kind of quadruple responsive nano compound according to claim 1, it is characterised in that the reduction-oxidation graphite
Alkene-meso-porous titanium dioxide silicon compound is that graphene oxide is reduced in buck, with cetyl trimethylammonium bromide as template,
Redox graphene-meso-porous titanium dioxide silicon compound is hydrolyzed to form by tetraethyl orthosilicate.
5. the preparation method of quadruple responsive nano compound as claimed in claim 1, it is characterised in that comprise the following steps that：
1) redox graphene-meso-porous titanium dioxide silicon compound is prepared：By 40~60 milligrams of graphene oxides in 500~700W
2~3h of ultrasound is smashed in the ultrasonic machine of power；Broken graphene oxide is dispersed in the buck of pH=11~12,75~
85 DEG C of oil bath stirring 12h are reduced, and are subsequently adding 1.5~2.0 grams of cetyl trimethylammonium bromide and are adjusted pH=
11.8~12 stirrings 30 minutes, are eventually adding 850~900 microlitres of tetraethyl orthosilicates and continue to stir 24h in 75~85 DEG C of oil baths, from
Redox graphene-meso-porous titanium dioxide silicon compound is obtained after the heart；
2) compound is surface-functionalized：By step 1) 230~270 milligrams of compounds obtaining are distributed in toluene, 75~
Stirred under 85 DEG C of oil baths 30 minutes, 2~3 milliliters of isocyanatopropyl triethoxysilanes are then added dropwise and flow back 24 hours, it is centrifugation, clear
Wash, be vacuum dried；The product that will be obtained is distributed in 25~30 milliliters of DMFs, and double (2- hydroxyls are then added dropwise
Ethyl) disulfide, oil bath is stirred 24~36 hours at 75~85 DEG C, centrifugation, cleaning, vacuum drying；By above-mentioned product again
Be distributed in 20 milliliters of anhydrous tetrahydro furans, ice bath, when temperature is cooled to 0 DEG C, add 0.8~0.9 milliliter triethylamine and
The bromo- 2- methyl propionyl bromides of 2-, after 0 DEG C is reacted 2~3 hours, are then transferred to react 24~36 hours, wherein isocyanic acid third at room temperature
The mol ratio of ethyl triethoxy silicane alkane, double (2- hydroxyethyls) disulfides and the bromo- 2- methyl propionyl bromides of 2- is 1:1:1~2；
3) removing template is removed：The product that step 2 is obtained is re-dispersed into the ethanol solution of 0.6wt% ammonium nitrate, 70~80 DEG C
Backflow 2~3 hours, repeat this step 3 time be centrifuged afterwards, clean, be vacuum dried after it is standby；
4) by step 3) surface-functionalized 230~270 milligram redox graphene-mesoporous silicon oxide for obtaining is combined
Thing, 6~6.8 milliliters of dimethylaminoethyl methacrylates and 25~28 milligrams of cuprous bromides, are distributed to dry 12 milliliters of N,
In dinethylformamide, it is placed in Schlenk flask, is noted 52~57 microlitre of three (2- dimethylaminoethyls) amine with syringe
Be mapped in Schlenk flask, after " freezing-pumping-thaw " five to eight circulations in temperature is 75~85 DEG C of oil baths reaction 48~
60 hours, after being then centrifuged for, clean, being vacuum dried, obtain quadruple responsive nano compound, wherein cuprous bromide, three (2- bis-
Methylaminoethyl) mol ratio of amine and dimethylaminoethyl methacrylate is 1:1:175~200.
6. the preparation method of nano-complex according to claim 5, it is characterised in that the step 1) in, graphite oxide
The preparation method of alkene is improved Hummer ' s methods：Sodium chloride of 1 gram of the natural graphite flakes with 60 grams grinds in being blended in grinding body,
Mix suction filtration after sodium dissolving to be chlorinated with 1~2 liter of water again, the graphite that will be obtained is in 80~90 DEG C of dried in vacuum overnight；It is dry
Stirred 8~12 hours under graphite flake and the 98% of 23 milliliters H2SO2 mixed room temperatures, 3 grams are slowly added under condition of ice bath
Potassium permanganate, then stirred 30 minutes in 38~42 DEG C of oil baths, it is heated to 70~80 DEG C and is incubated 45 minutes, it is subsequently adding 3 milliliters
Deionized water, add 3 ml deionized waters after being heated to 100~105 DEG C of insulations 5 minutes, insulation adds 40 millis after 5 minutes
The deionized water for rising, maintains temperature at 100~105 DEG C, and 140 ml deionized waters and 10 milliliter 30% are added after 15 minutes
H2O2 terminating reactions, obtain graphene oxide after centrifugation.
7. the application of quadruple responsive nano compound as claimed in claim 1, it is characterised in that be dispersed in nano-complex
In deionized water, concentration 5mg/ml, while add 50 milligrams of water miscible guest molecules, with magnetic stirrer 24 hours,
After loading process terminates, the removal of dialysis 48~60 hours is carried out with the bag filter of molecular cut off 3500 most of without being loaded into
The guest molecule for going, is then repeatedly centrifuged untill the supernatant being centrifuged out does not have fluorescence, and freeze-drying obtains medicine and releases
Put controllable guest molecule.
8. the application of quadruple responsive nano compound according to claim 7, it is characterised in that the guest molecule is sieve
Red bright B.
9. the application of quadruple responsive nano compound according to claim 7, it is characterised in that the guest molecule is near
Infrared light, temperature, pH and reduction quadruple response release are controllable.
10. the application of quadruple responsive nano compound according to claim 7, it is characterised in that insoluble drug release is controllable
Under near infrared light, the heat energy that the graphene oxide of reduction is produced opens the polymer shrink of temperature-responsive to guest molecule
Duct, guest molecule release.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710092318.0A CN106916266A (en) | 2017-02-21 | 2017-02-21 | A kind of preparation and its application of quadruple responsive nano compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710092318.0A CN106916266A (en) | 2017-02-21 | 2017-02-21 | A kind of preparation and its application of quadruple responsive nano compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106916266A true CN106916266A (en) | 2017-07-04 |
Family
ID=59453879
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710092318.0A Pending CN106916266A (en) | 2017-02-21 | 2017-02-21 | A kind of preparation and its application of quadruple responsive nano compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106916266A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109608985A (en) * | 2018-12-08 | 2019-04-12 | 郑州师范学院 | One kind can be automatically repaired corrosion-inhibiting coating and preparation method thereof |
| CN112057747A (en) * | 2020-08-17 | 2020-12-11 | 深圳市智为时代科技有限公司 | Graphene material for hot compress material and preparation method thereof |
| CN116218270A (en) * | 2023-02-27 | 2023-06-06 | 中海油常州涂料化工研究院有限公司 | Dual-response anticorrosive filler and preparation method and application thereof |
| CN116285463A (en) * | 2023-03-24 | 2023-06-23 | 常州大学 | Anticorrosive filler with intelligent response and preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103601863A (en) * | 2013-11-21 | 2014-02-26 | 南通茂林医用材料有限公司 | Preparation method of pH-responsive graphene/polymer nanometer hybrid material |
| CN104072694A (en) * | 2014-06-20 | 2014-10-01 | 北京科技大学 | Preparation method and application of quadruple-responsiveness block micelle |
| CN105153381A (en) * | 2015-09-06 | 2015-12-16 | 江南大学 | Novel method for modifying graphene with polymer |
| CN105997944A (en) * | 2016-07-07 | 2016-10-12 | 上海理工大学 | Nano-drug carrier with magnetothermal and photothermal effects and preparation method thereof |
-
2017
- 2017-02-21 CN CN201710092318.0A patent/CN106916266A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103601863A (en) * | 2013-11-21 | 2014-02-26 | 南通茂林医用材料有限公司 | Preparation method of pH-responsive graphene/polymer nanometer hybrid material |
| CN104072694A (en) * | 2014-06-20 | 2014-10-01 | 北京科技大学 | Preparation method and application of quadruple-responsiveness block micelle |
| CN105153381A (en) * | 2015-09-06 | 2015-12-16 | 江南大学 | Novel method for modifying graphene with polymer |
| CN105997944A (en) * | 2016-07-07 | 2016-10-12 | 上海理工大学 | Nano-drug carrier with magnetothermal and photothermal effects and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| YI WANG等: "Multifunctional Mesoporous Silica-Coated Graphene Nanosheet Used for Chemo-Photothermal Synergistic Targeted Therapy of Glioma", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
| 杨鑫超: "甲基丙烯酸酯类高性能基因载体的构建、制备与表征", 《中国博士学位论文全文数据库 医药卫生科技辑》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109608985A (en) * | 2018-12-08 | 2019-04-12 | 郑州师范学院 | One kind can be automatically repaired corrosion-inhibiting coating and preparation method thereof |
| CN112057747A (en) * | 2020-08-17 | 2020-12-11 | 深圳市智为时代科技有限公司 | Graphene material for hot compress material and preparation method thereof |
| CN116218270A (en) * | 2023-02-27 | 2023-06-06 | 中海油常州涂料化工研究院有限公司 | Dual-response anticorrosive filler and preparation method and application thereof |
| CN116285463A (en) * | 2023-03-24 | 2023-06-23 | 常州大学 | Anticorrosive filler with intelligent response and preparation method and application thereof |
| CN116285463B (en) * | 2023-03-24 | 2024-01-23 | 常州大学 | Anticorrosive filler with intelligent response and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106916266A (en) | A kind of preparation and its application of quadruple responsive nano compound | |
| CN107055553A (en) | A kind of mesoporous silica nano-particle of the dual modification of mercapto carboxy and preparation method thereof | |
| CN110038529A (en) | A kind of preparation method of three-dimensional fiber base composite aerogel type adsorbent | |
| CN100446134C (en) | Method for preparing iron-oxide particle suspension | |
| CN105903016A (en) | Preparing method of core-shell structure drug carrier with near-infrared light exciting supermolecule valve light control drug release | |
| CN102727901A (en) | Graphene oxide/hyaluronic acid nanometer drug carrier material, preparation method and application of graphene oxide/hyaluronic acid nanometer drug carrier material | |
| CN107242996B (en) | A kind of gel rubber material and preparation method thereof for oncotherapy | |
| CN107510842A (en) | A kind of preparation method of complex light thermit powder clean and with excellent photo-thermal effect | |
| CN113941009B (en) | Metal organic framework nano-carrier and preparation method and application thereof | |
| CN107233301A (en) | A kind of fast preparation method of nano particle gel drug-loading system | |
| CN107275112B (en) | Irradiation method prepares MnO2The method for adulterating bamboo charcoal based super capacitor electrode material | |
| CN108939069A (en) | A kind of nano drug-carrying medicine-releasing system and preparation method thereof degradable without closure | |
| CN108553644A (en) | The more stimuli responsive type pharmaceutical carriers of double valve and preparation method thereof based on mesoporous silicon/cyclodextrin/Zinc oxide quantum dot structure | |
| CN108743971B (en) | Preparation method and application of drug-loaded polypyrrole nanoparticles | |
| CN102921359A (en) | Preparation method of biological capsule for sewage treatment | |
| CN105963274A (en) | Preparation method of methylene blue containing silicon dioxide/tannin-iron particles promoting methylene blue monomer release | |
| CN108785276A (en) | A kind of purposes of radio therapy sensitization nano material | |
| CN104690290A (en) | Preparation method of wave-absorbing composite material with graphene loaded with nano nickel | |
| CN105148271A (en) | Near-infrared light stimulation controllably responsive photo-thermal microcapsule having thermal therapy/chemotherapy double actions and preparation method of microcapsule | |
| CN1392168A (en) | Process for preparing high water absorption resin | |
| CN105797688A (en) | Preparation method and application of gel particle adsorbent | |
| CN106390132B (en) | A kind of temperature sensitive polymer@graphene oxide pharmaceutical capsules carrier and its preparation method and application | |
| CN107244667B (en) | A kind of amphipathic aeroge and preparation method | |
| CN206778419U (en) | High dispersive reactor is used in a kind of ferric phosphate production | |
| CN206045016U (en) | The Preparation equipment of modification SiO2 nano-carriers |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170704 |
|
| RJ01 | Rejection of invention patent application after publication |