CN106421784A - Nano drug carrier having photothermal effect and preparation method and application thereof - Google Patents
Nano drug carrier having photothermal effect and preparation method and application thereof Download PDFInfo
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- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
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- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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Abstract
The invention provides a nano drug carrier having a photothermal effect, wherein the nano drug carrier includes a metal organic framework and graphene oxide, wherein the metal organic framework is formed by self-assembly of an organic ligand and metal ions or metal clusters through coordination bonds, and the graphene oxide is embedded in the metal organic framework; the particle size of nano drug carrier particles is 30-500 nm. The invention also provides a preparation method of the nano drug carrier and an application of the nano drug carrier in loading of an anticancer drug. Because the nano drug carrier has the metal organic framework, the nano drug carrier provided by the invention can be used as a drug carrier; moreover, because the nano drug carrier has the graphene oxide embedded in the metal organic framework, the nano drug carrier can efficiently convert light and heat and is suitable for thermal therapy of cancer, and the thermal therapy also can improve the activity of a part of chemotherapy drugs to enhance the curative effect of the chemotherapy drugs; therefore, the nano drug carrier can allow thermal therapy on the cancer and drug therapy to be combined together, so as to improve the curative effect of the cancer.
Description
Technical field
The present invention relates to a kind of have the nano-medicament carrier of photo-thermal effect, the preparation method of this nano-medicament carrier and be somebody's turn to do
The application of nano-medicament carrier, belongs to pharmaceutical technology field.
Background technology
Treatment of cancer is always clinical problem, it has also become the primary disease causing human death in addition to cardiovascular and cerebrovascular disease
Disease.According to the World Health Organization (World Health Organization, WHO) report, global cancer morbidity and the death rate are all
In steeply rising trend, there are up to ten million people every year because cancer mortality, and the cancer new cases in the whole world about 60% are sent out
Life is in developing country.The treatment means of cancer have at present：Surgical operation therapy, radiotherapy, chemotherapy and biology
Treatment etc..Wherein, chemotherapy is the conventional means in treatment of cancer, but chemotherapeutics toxicity is big, and Formulations for systemic administration often goes out
It is existing that utilization ratio of drug is low, cause serious toxic and side effect and multidrug resistance.Therefore, design multi-functional pharmaceutical carrier,
While Drug controlled release is to improve utilization ratio of drug and to reduce toxic and side effect, using other cancers such as thermotherapy, gene therapy
Treatment means, to obtain the synergy with chemotherapy, are greatly improved treatment of cancer effect.
Thermotherapy has been widely accepted as a kind of effective cancer treatment method.Thermotherapy is exactly to make the tumor locus of patient
Temperature rises to 43 DEG C～48 DEG C, under this temperature environment, is afraid of that the cancer cell of " hot " by hyperpyrexia direct killing apoptosis, and will align
Often tissue does not injure.The temperature that normal structure can bear is higher than the temperature that cancer cell is subject to bear, and therefore can pass through office
Portion's high temperature optionally to kill cancer cell.In addition, research also indicates that, thermotherapy can also activate the siberian crabapple being in palsy
System, produces antineoplastic immune, thus suppression and killing MET or subclinical focus.In addition, thermotherapy can improve part
The curative effect to strengthen chemotherapeutics for the activity for the treatment of medicine.Therefore, chemotherapy and combined with hyperthermia use can obtain treatment of cancer
Cooperative effect, improves therapeutic effect.
Metal-organic framework material (Metal-Organic Frameworks, MOFs) is by organic ligand and metal ion
Or the hybrid inorganic-organic materials with molecule inner pore that cluster is self-assembly of by coordinate bond, have high surface and
Pore volume, structure are adjustable, be easy to chemical modification.Research shows, Zn, Fe, Zr plasma is that the MOF material of metal ion has biology
Compatibility, can a large amount storing drugs obtain controlled insoluble drug release behavior, and degradability in specific environment.Separately
Outward, metal-organic framework material preparation technology in recent years can achieve the controllable standby of metal organic frame nano particle, and this has
It is used for drug-delivery applications beneficial to as carrier.Therefore, metal-organic framework material shows huge diving in biomedical sector
Power.
Graphene oxide (graphene oxide, GO) is product after chemical oxidation and stripping for the powdered graphite, and GO is
Single atomic layer, after oxidation processes, GO still keeps the layer structure of graphite, but in each layer of graphene oxide monolithic
On introduce many epoxide functional groups, such as-OH ,-COOH ,-O- etc., these groups can be interacted with a lot of materials, formation
Composite.On the other hand, graphene oxide have extremely wide from ultraviolet to the light absorbs of near-infrared (UV-NIR), in NIR area
Strong row light absorbs make graphene oxide have high photo-thermal conversion efficiency.Study and also indicated that, graphene oxide is in cancer
The photo-thermal therapy aspect of disease has potential application.
Therefore, how to design and prepare graphene oxide and metal organic frame composite nanometer particle and become acquisition cancer therapy drug
Convey and work in coordination with the key of photo-thermal therapy.
Content of the invention
It is an object of the invention to provide a kind of nano-medicament carrier with photo-thermal effect, preparation method and application, with same
When meet chemotherapy and photo-thermal therapy function.
To achieve these goals, the technical solution adopted in the present invention is：
A kind of nano-medicament carrier with photo-thermal effect is it is characterised in that include：Metal organic frame, this metal has
Machine frame is to be self-assembly of by coordinate bond by organic ligand and metal ion or metal cluster；And, graphene oxide, embedding
Enter inside metal organic frame.
The nano-medicament carrier with photo-thermal effect involved in the present invention can also have the feature that：Nano medication
The grain diameter of carrier is 30～500 nanometers.
The nano-medicament carrier with photo-thermal effect involved in the present invention can also have the feature that：Metal ion
Or the metal of metal cluster is any one in Zn, Fe, Cu, Co, Ni, Cr, Zr, Sr.
The nano-medicament carrier with photo-thermal effect involved in the present invention can also have the feature that：Organic ligand
For 2-methylimidazole, benzenetricarboxylic acid, terephthalic acid (TPA), nitroterephthalic, amino terephthalic acid (TPA), muconic acid and anti-
Any one in butene dioic acid.
And, present invention also offers a kind of prepare the metal organic frame/stannic oxide/graphene nano with photo-thermal effect
The method of pharmaceutical carrier, comprises the following steps：
Step one, by 2-methylimidazole with predetermined solvent with 0.2g～2g：The ratio of 25ml is mixed, and carry out 10～
The magnetic agitation of 40 minutes obtains 2-methylimidazole solution, then by zinc nitrate hexahydrate (Zn (NO3) 2.6H2O) and predetermined solvent
With 0.2g～2g：The ratio of 51ml carries out being mixed to get zinc nitrate hexahydrate solution, is then added dropwise to 2-methylimidazole solution
In, react 20～40 minutes, obtain reaction solution, wherein, the 2-methylimidazole solution of addition is mixed with zinc nitrate hexahydrate solution
Closing volume ratio is 1～10:1；
Step 2, by graphene oxide with predetermined solvent with 0.2mg～2mg：The ratio of 1ml carries out being mixed to get oxidation stone
Black alkene solution, is subsequently adding reaction solution and continues stirring 1～4 hour, obtain resultant solution, wherein, the graphite oxide of addition
The mixed volume of alkene solution and reaction solution is than for 1～10:100；
Step 3, is centrifuged to product solution body, and it is washed at least one times with water, carries out vacuum to it
It is dried, obtain described nano-medicament carrier.
The method that the preparation that the present invention provides has the nano-medicament carrier of photo-thermal effect, can also have such spy
Levy：Solvent in methyl imidazole solution, zinc nitrate hexahydrate (Zn (NO3) 2.6H2O) solution and graphene oxide solution is predetermined
Solvent, predetermined solvent is any one in water, ethanol, methyl alcohol and ethanol methyl alcohol mixed liquor.
And, present invention also offers the above-mentioned nano-medicament carrier with photo-thermal effect is as the carrier of cancer therapy drug
Application.
The above-mentioned application that the present invention provides, can also have the feature that：Cancer therapy drug is adriamycin.
Invention effect and effect
According to what the present invention provided, there is nano-medicament carrier of photo-thermal effect and preparation method thereof, the nanometer medicine prepared
Thing carrier, due to having metal organic frame, as pharmaceutical carrier, and can be embedded in institute because this nano-medicament carrier has
State the graphene oxide within metal organic frame so that this nano-medicament carrier efficiently can be changed to photo-thermal, suitably
The thermotherapy of cancer, and thermotherapy can improve the activity of the part chemotherapeutics curative effect to strengthen chemotherapeutics, so this nanometer of medicine
Thing carrier, as the carrier of cancer therapy drug, can will combine to the thermotherapy of cancer and chemotherapy, improve and cancer is controlled
Therapeutic effect.
Brief description
Fig. 1 strafes Electronic Speculum (SEM) figure for the nano-medicament carrier with photo-thermal effect of embodiment one preparation；
Fig. 2 strafes Electronic Speculum (SEM) figure for the nano-medicament carrier with photo-thermal effect of embodiment two preparation；
Fig. 3 strafes Electronic Speculum (SEM) figure for the nano-medicament carrier with photo-thermal effect of embodiment three preparation；
Fig. 4 is the photo-thermal heating curve of the nano-medicament carrier with photo-thermal effect of embodiment one preparation；
Fig. 5 is the column of the cytotoxicity result contrast of the nano-medicament carrier with photo-thermal effect of embodiment one preparation
Figure；
Fig. 6 is the adriamycin medicine release concentration curve of the nano-medicament carrier with photo-thermal effect having loaded adriamycin
Figure；
Fig. 7 is the cell phagocytosis figure of the nano-medicament carrier particle with photo-thermal effect having loaded adriamycin；
The nano-medicament carrier with photo-thermal effect that Fig. 8 is 4T1 cell, adriamycin medicine, embodiment one prepare
With loaded adriamycin have the nano-medicament carrier of photo-thermal effect respectively under Infrared irradiation inhibition cancer cell effect
The block diagram of contrast.
Specific embodiment
Below in conjunction with accompanying drawing, to a kind of nano-medicament carrier with photo-thermal effect involved in the present invention, preparation method
And application is described further.
Experimental technique used in following embodiments if no special instructions, is conventional method；The raw material that used, appearance
Device, equipment etc., if no special instructions, all commercially obtain.
<Embodiment one>
The present embodiment is the method for the nano-medicament carrier that preparation has photo-thermal effect, comprises the following steps：
Step one：2 grams of 2-methylimidazoles are dissolved in magnetic agitation in 50ml deionized water and after 15 minutes, form settled solution；
Then by 0.95 gram of zinc nitrate hexahydrate aqueous solution 50 milliliters be added dropwise in above-mentioned reactant liquor, continue reaction 30 minutes；
Step 2：The oxidation graphene oxide water of 1 milliliter of 0.5 mg/ml is added in the reaction system of step one
Solution, continues stirring reaction 1 hour, obtains product；
Step 3：To product centrifugation, and cleaned with water three times, be vacuum dried at 37 DEG C, obtaining metal has
Machine frame/stannic oxide/graphene nano pharmaceutical carrier.
Nano-medicament carrier particle contour analysis：
Fig. 1 strafes Electronic Speculum (SEM) figure for the nano-medicament carrier with photo-thermal effect of embodiment one preparation.
As shown in figure 1, being carried out using strafing the nano-medicament carrier with photo-thermal effect that Electronic Speculum obtains to the present embodiment
Strafe, Electronic Speculum (SEM) figure of strafing obtaining shows this nano-medicament carrier particle spherical in shape, particle diameter about 60 ran, divides
Scattered property is good.
<Embodiment two>
The present embodiment is the method for the nano-medicament carrier that preparation has photo-thermal effect, comprises the following steps：
Step one：2 grams of 2-methylimidazoles are dissolved in magnetic agitation in 50ml deionized water and after 15 minutes, form settled solution；
Then by 0.95 gram of zinc nitrate hexahydrate aqueous solution 50 milliliters be added dropwise in above-mentioned reactant liquor, continue reaction 30 minutes；
Step 2：Add the oxidation graphene oxide of 2 milliliters of 1 mg/ml water-soluble in the reaction system of step one
Liquid, continues stirring reaction 1 hour, obtains product；
Step 3：To product centrifugation, and cleaned with water three times, be vacuum dried at 37 DEG C, obtaining metal has
Machine frame/stannic oxide/graphene nano pharmaceutical carrier.
Nano-medicament carrier particle contour analysis：
Fig. 2 strafes Electronic Speculum (SEM) figure for the nano-medicament carrier with photo-thermal effect of embodiment two preparation.
As shown in Fig. 2 being carried out using strafing the nano-medicament carrier with photo-thermal effect that Electronic Speculum obtains to the present embodiment
Strafe, Electronic Speculum (SEM) figure of strafing obtaining shows this nano-medicament carrier particle spherical in shape, particle diameter about 210 ran, divides
Scattered property is good.
<Embodiment three>
The present embodiment is the method for the nano-medicament carrier that preparation has photo-thermal effect, comprises the following steps：
Step one：2 grams of 2-methylimidazoles are dissolved in magnetic agitation in 50ml deionized water and after 15 minutes, form settled solution；
Then by 0.95 gram of zinc nitrate hexahydrate aqueous solution 50 milliliters be added dropwise in above-mentioned reactant liquor, continue reaction 30 minutes；
Step 2：The oxidation graphene oxide water of 3 milliliters of 1.5 mg/ml is added in the reaction system of step one
Solution, continues stirring reaction 1 hour, obtains product；
Step 3：To product centrifugation, and cleaned with water three times, be vacuum dried at 37 DEG C, obtaining metal has
Machine frame/stannic oxide/graphene nano pharmaceutical carrier.
Nano-medicament carrier particle contour analysis：
Fig. 3 strafes Electronic Speculum (SEM) figure for the nano-medicament carrier with photo-thermal effect of embodiment three preparation.
As shown in figure 3, being carried out using strafing the nano-medicament carrier with photo-thermal effect that Electronic Speculum obtains to the present embodiment
Strafe, Electronic Speculum (SEM) figure of strafing obtaining shows this nano-medicament carrier particle spherical in shape, particle diameter about 450 ran, divides
Scattered property is good.
Product analysis
Photo-thermal effect test and cytotoxicity test：
The nano-medicament carrier with photo-thermal effect that the present embodiment is prepared carries out fuel factor test and cell toxicant
Property test.
The nano-medicament carrier with photo-thermal effect using following photo-thermal effect analysis of test methods the present embodiment
Photo-thermal effect：
Take 5 parts of above-mentioned nano-medicament carriers, 5 milligrams every part, be respectively put in 96 orifice plates, the infrared light using 808nm exists
Do not put the orifice plate of nano-medicament carrier and be irradiated to the orifice plate having put nano-medicament carrier and under different capacity, observe this and receive
The temperature variations on rice pharmaceutical carrier surface, and be depicted as curve to observe the photo-thermal intensification effect of nano-medicament carrier
Really.
Fig. 4 is the photo-thermal heating curve figure of the nano-medicament carrier with photo-thermal effect of embodiment one preparation.
As can be seen from Figure 4 the control group being not added with this nano-medicament carrier is 1.5w/cm in infrared luminous power2Illumination
Under temperature have almost no change, and added the orifice plate of nano-medicament carrier under the irradiation of infrared light, temperature rise effect substantially, and
And heating rate accelerates with the increase of power.When infrared luminous power is 2.5w/cm2When, irradiating through 5 minutes to make particle
Temperature is increased to 53 DEG C from 30 DEG C, meets the requirement to temperature for the thermotherapy.
Analyze the nano-medicament carrier with photo-thermal effect of the present embodiment using following cytotoxicity assay
Cytotoxicity：
Vitro cytotoxicity measures the Cell Counting Kit-8 method using standard.Cell uses mouse
Breast cancer cell (4T1 cell), specific experiment process is as follows：
4T1 cell is sowed after in 96 orifice plates (5000/hole of cell density), Nano medication prepared by embodiment one
Support dispersion in DMEM nutrient solution and be configured to concentration be 25,50,100 and 200 mcg/ml nano-medicament carrier suspend
Liquid, is then added into 96 orifice plates, and the suspension of every kind of concentration respectively adds 12 holes, respectively adds 100 microlitres in each hole.Culture 24
To in each hole, after hour, add 10 microlitres of CCK-8 solution, cell measures 450 nanometers with ELIASA after continuing culture 2 hours
Absorbance at wavelength.
The living cells of 4T1 cell that nano-medicament carrier suspension was processed is processed with not having nano-medicament carrier suspension
The percentage compared of living cells of 4T1 cell be expressed as cytotoxicity.
Fig. 5 is the cytotoxicity test Comparative result of the nano-medicament carrier with photo-thermal effect of embodiment one preparation
Block diagram.
Fig. 5 shows that the toxicity of nano-medicament carrier particle is less, and the cell survival rate in 200 mcg/ml all reaches
To more than 90%, show that nano-medicament carrier has good biocompatibility, drug delivery can be used for as carrier.
Products application is analyzed：
When the nano-medicament carrier with photo-thermal effect manufactured in the present embodiment is applied as the carrier of cancer therapy drug, permissible
By the steps, cancer therapy drug is stored in this carrier：
Step one：2 grams of 2-methylimidazoles are dissolved in magnetic agitation in 50ml deionized water and after 15 minutes, form settled solution,
It is subsequently added into the adriamycin aqueous solution of 20 milliliters of 2 mg/ml, and continue stirring 15 minutes under dark condition；
Step 2：By 0.95 gram of zinc nitrate hexahydrate aqueous solution, 50 milliliters are added dropwise in the reactant liquor of step one, continue anti-
Answer 30 minutes, obtain product；
Step 3：The oxidation graphene oxide water of 1 milliliter of 1.5 mg/ml is added in the product of step 2
Solution, continues reaction 1 hour, obtains product；
Step 4：Product is centrifuged, and it is cleaned three times with water, at 37 DEG C, it is vacuum dried,
Obtain the nano-medicament carrier with photo-thermal effect having loaded adriamycin.
Insoluble drug release has been carried out to the above-mentioned nano-medicament carrier with photo-thermal effect having loaded anticancer drugs, doxorubicin
Test and cell phagocytosis test：
The photo-thermal effect that has having loaded adriamycin using following insoluble drug release analysis of test methods the present embodiment
The photo-thermal effect of nano-medicament carrier：
2 milliliters of (pH value is 4.5,6.0 and 7.4) PBS solution are taken to be added in 3 centrifuge tubes respectively, above-mentioned negative by 4 milligrams
The nano-medicament carrier with photo-thermal effect having carried adriamycin is respectively put in above-mentioned three centrifuge tubes, lucifuge pair at 37 DEG C
It carries out DOX release experiment respectively；With the time interval selected, delivery systme is centrifuged respectively, and extracts 3 respectively
Microlitre supernatant is used for ultraviolet-visible light and analyzes, the absorbance of contained DOX in detection buffer solution, test repetition three every time
Secondary, take the mean value of three times as final absorbance.
Calculate the concentration of DOX according to the calibration curve of the DOX concentration completed and absorbance relation in advance.
Finally calculate the relation of the DOX insoluble drug release concentration under different PH and release time, be depicted as medicine releasability
Can curve map.
Fig. 6 is the adriamycin medicine release concentration curve of the nano-medicament carrier with photo-thermal effect having loaded adriamycin
Figure.
This test to detect the nano-medicament carrier having loaded adriamycin not using PBS cushioning liquid as simulated body fluid
With the insoluble drug release behavior under pH value.
As can be seen from Figure 6 the adriamycin medicine release concentration of this nano-medicament carrier rises with the reduction of pH value
Height, wherein, when pH value is 7.4, release concentration is only 10% about, and the release concentration when pH value is 6.0 reaches
70%, the release concentration when pH value is 4.5 has reached 80%, shows that this nano-medicament carrier has PH control release function,
Achievable nano-medicament carrier less release anti-cancer medicine before entering cell, and cancer therapy drug after entering cell, can be obtained
Very fast release.
Using following cell swallow analysis of test methods the present embodiment loaded anticancer drugs, doxorubicin there is light
The cell phagocytosis situation of the nano-medicament carrier of fuel factor：
1.5 × 105 4T1 cells are seeded in the culture vessel with glass bottom of a 35mm, cultivate 24 hours；By above-mentioned nanometer
Pharmaceutical carrier is added in DMEM cell culture fluid, and ultimate density is 100 mcg/ml, subsequently this is contained nano-medicament carrier
Cell culture fluid be added in above-mentioned culture vessel with glass bottom and cultivate 1 hour, 2 hours and 4 hours respectively, wash 2 respectively with PBS
After secondary, DAPI methanol solution is added after dyeing 15 minutes, to add methyl alcohol to fix cell；Finally, with the micro- sem observation of confocal fluorescent
The situation of cell this nano-medicament carrier of each autophagy.
Fig. 7 is the cell phagocytosis figure of the nano-medicament carrier particle with photo-thermal effect having loaded adriamycin.Wherein,
Fig. 7-A-1～Fig. 7-A-3 is the cell phagocytosis figure of this nano-medicament carrier after cultivating 1 hour；
Fig. 7-B-1～Fig. 7-B-3 is the cell phagocytosis figure of this nano-medicament carrier after cultivating 2 hours；
Fig. 7-C-1～Fig. 7-C-3 is the cell phagocytosis figure of this nano-medicament carrier after cultivating 4 hours.
Can be seen that this nano-medicament carrier is distributed in the cell from each in figure of Fig. 7, show that cell can swallow load
The nano-medicament carrier with photo-thermal effect of adriamycin.
What 4T1 cell, adriamycin medicine, embodiment one prepared has nano-medicament carrier and the load of photo-thermal effect
The nano-medicament carrier with photo-thermal effect of adriamycin has carried out photo-thermal effect test respectively, and specific experiment flow process is as follows：
4T1 cell is sowed after in 96 orifice plates (5000/hole of cell density), cultivates 24 hours；By adriamycin medicine,
The nano-medicament carrier of what embodiment one prepared have photo-thermal effect and loaded adriamycin there is receiving of photo-thermal effect
Rice pharmaceutical carrier is added separately in DMEM cell culture fluid, forms the suspension that concentration is 100 mcg/ml, by this three kinds
Suspension is added separately in 96 orifice plates of above-mentioned sowing cell continue culture 8 hours；Then infrared light photograph is carried out to each hole
Penetrate 3 minutes, be further cultured for 4 hours；Add 10 microlitres of CCK-8 solution in each hole, cell continues culture 2 hours；Finally use
ELIASA measures the absorbance of their 450 nanometer wave strong points, measures respective cell survival rate with it.
The nano-medicament carrier with photo-thermal effect that Fig. 8 is 4T1 cell, adriamycin medicine, embodiment one prepare
With loaded adriamycin have the nano-medicament carrier of photo-thermal effect respectively under Infrared irradiation inhibition cancer cell effect
The block diagram of contrast.
As can be seen from Figure 8,4T1 cell and adriamycin medicine plus light and the cell being not added with two groups of control groups of light
Survival rate is more or less the same；There is the nano-medicament carrier of photo-thermal effect and loaded Ah mould to added that embodiment one prepares
The Infrared irradiation carrying out 808nm in two groups of cells of the nano-medicament carrier with photo-thermal effect of plain medicine is after 3 minutes, carefully
Born of the same parents are most of dead, and loaded adriamycin medicine there is the nano-medicament carrier of photo-thermal effect after irradiation, cell is deposited
Motility rate is minimum, and only 18%, show that chemotherapy and combined with hyperthermia use can obtain the cooperative effect for the treatment of of cancer.
The beneficial effect of embodiment and effect
According to what the present embodiment provided, there is nano-medicament carrier of photo-thermal effect and preparation method thereof, the nanometer prepared
Pharmaceutical carrier, due to having metal organic frame, as pharmaceutical carrier, and can be embedded in because this nano-medicament carrier has
Graphene oxide within described metal organic frame, so that this nano-medicament carrier efficiently can be changed to photo-thermal, is fitted
The thermotherapy of suitable cancer, and thermotherapy can improve the activity of the part chemotherapeutics curative effect to strengthen chemotherapeutics, so this nanometer
Pharmaceutical carrier, as the carrier of cancer therapy drug, can will be treated and combine to the thermotherapy of cancer and medicine, improve and cancer is controlled
Therapeutic effect；
Again due to the present embodiment nano-medicament carrier with the exposure intensity of infrared light change, its temperature can be notable
Change it is possible to regulate and control the photo-thermal effect of nano-medicament carrier by controlling near infrared light intensity；
Again because the nano-medicament carrier of the present embodiment has the function of PH Drug controlled release concentration, achievable nanometer medicine
Thing carrier less release anti-cancer medicine before entering cell, and the very fast release of cancer therapy drug after entering cell, can be obtained, from
And improve the efficiency killing cancer cell.
Certainly, a kind of metal organic frame/stannic oxide/graphene nano medicine with photo-thermal effect involved in the present invention
Carrier, preparation method and application are not merely defined in the content in above-described embodiment one and embodiment two.Above content is only
Basic explanation under present inventive concept, and according to any equivalent transformation that technical scheme is made, belong to the present invention
Protection domain.
Claims (8)
1. a kind of nano-medicament carrier with photo-thermal effect is it is characterised in that include：
Metal organic frame, this metal organic frame passes through coordinate bond self assembly by organic ligand and metal ion or metal cluster
Formed；And
Graphene oxide, is embedded in inside described metal organic frame.
2. the nano-medicament carrier with photo-thermal effect according to claim 1 it is characterised in that：
Wherein, the grain diameter of described nano-medicament carrier is 30～500 nanometers.
3. the nano-medicament carrier with photo-thermal effect according to claim 1 it is characterised in that：
Wherein, the metal of described metal ion or metal cluster is any one in Zn, Fe, Cu, Co, Ni, Cr, Zr, Sr.
4. the nano-medicament carrier with photo-thermal effect according to claim 1 it is characterised in that：
Wherein, described organic ligand is 2-methylimidazole, benzenetricarboxylic acid, terephthalic acid (TPA), nitroterephthalic, amino to benzene
Any one in dioctyl phthalate, muconic acid and fumaric acid.
5. the preparation method of the nano-medicament carrier with photo-thermal effect as described in Claims 1-4 for the preparation, its feature exists
In comprising the following steps：
Step one, by 2-methylimidazole with predetermined solvent with 0.2g～2g：The ratio of 25ml is mixed, and carries out 10～40 points
The magnetic agitation of clock obtains 2-methylimidazole solution, then by zinc nitrate hexahydrate (Zn (NO3)2.6H2O) with described predetermined solvent with
0.2g～2g：The ratio of 51ml carries out being mixed to get zinc nitrate hexahydrate solution, is then added dropwise to described 2-methylimidazole molten
In liquid, react 20～40 minutes, obtain reaction solution, wherein, the described 2-methylimidazole solution of addition and described six water nitric acid
The volume ratio of zinc solution is 1～10:1；
Step 2, by graphene oxide with described predetermined solvent with 0.2mg～2mg：The ratio of 1ml carries out being mixed to get oxidation stone
Black alkene solution, is subsequently adding described reaction solution and continues stirring 1～4 hour, obtain resultant solution, wherein, addition described
Graphene oxide solution is 1～10 with the volume ratio of described reaction solution:100；
Step 3, is centrifuged to described resultant solution body, and after it being washed at least one times with water, it is carried out very
Empty dry, obtain described nano-medicament carrier.
6. preparation method according to claim 5 it is characterised in that：
Wherein, described predetermined solvent is any one in water, ethanol, methyl alcohol and ethanol methyl alcohol mixed liquor.
7. nano-medicament carrier the answering as the carrier of cancer therapy drug with photo-thermal effect according to Claims 1-4
With.
8. according to claim 7 application it is characterised in that：
Wherein, described cancer therapy drug is adriamycin.
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| CN108079295A (en) * | 2017-12-30 | 2018-05-29 | 广西师范大学 | A kind of preparation method and applications of boron doping black zirconium dioxide nanoparticle |
| CN108281296A (en) * | 2018-01-24 | 2018-07-13 | 哈尔滨理工大学 | A method of improving metal-organic framework material chemical property in alkaline solution |
| CN108355166A (en) * | 2018-05-15 | 2018-08-03 | 黄冈师范学院 | A kind of mesopore bioactive glass/metal organic frame timbering material and preparation method |
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| WO2021177786A1 (en) * | 2020-03-06 | 2021-09-10 | 숙명여자대학교 산학협력단 | Metal-organic framework having variable structure and production method therefor |
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| CN108079295A (en) * | 2017-12-30 | 2018-05-29 | 广西师范大学 | A kind of preparation method and applications of boron doping black zirconium dioxide nanoparticle |
| CN108079295B (en) * | 2017-12-30 | 2020-02-07 | 广西师范大学 | Preparation method and application of boron-doped black zirconium dioxide nanoparticles |
| CN108281296A (en) * | 2018-01-24 | 2018-07-13 | 哈尔滨理工大学 | A method of improving metal-organic framework material chemical property in alkaline solution |
| CN108281296B (en) * | 2018-01-24 | 2019-09-20 | 哈尔滨理工大学 | A method of improving metal-organic framework material chemical property in alkaline solution |
| CN108555311A (en) * | 2018-04-18 | 2018-09-21 | 北京化工大学 | A kind of method that metal nanometer cluster is embedded in metal-organic framework materials by configurational ion induced growth |
| CN108355166A (en) * | 2018-05-15 | 2018-08-03 | 黄冈师范学院 | A kind of mesopore bioactive glass/metal organic frame timbering material and preparation method |
| CN108355166B (en) * | 2018-05-15 | 2021-02-19 | 黄冈师范学院 | Mesoporous bioactive glass/metal organic framework support material and preparation method thereof |
| CN110025596A (en) * | 2019-04-25 | 2019-07-19 | 上海理工大学 | A kind of Nano composite granules and preparation method thereof |
| WO2021177786A1 (en) * | 2020-03-06 | 2021-09-10 | 숙명여자대학교 산학협력단 | Metal-organic framework having variable structure and production method therefor |
| KR20210112914A (en) * | 2020-03-06 | 2021-09-15 | 숙명여자대학교산학협력단 | Variable structure metal-organic framework and manufacturing method thereof |
| KR102371886B1 (en) | 2020-03-06 | 2022-03-07 | 숙명여자대학교산학협력단 | Variable structure metal-organic framework and manufacturing method thereof |
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