CN108904473A - The modified photosensitizer nanocomposite of graphene oxide and its application - Google Patents
The modified photosensitizer nanocomposite of graphene oxide and its application Download PDFInfo
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Abstract
The invention belongs to medical use optical dynamic therapy field of material technology, and in particular to a kind of the photosensitizer nanocomposite and its application patent application matters of graphene oxide modification.The nanocomposite GO@TiO2@PS, when preparation include：The titanium oxide nanoparticles of one step wet process preparation load Photosan prepare the modified photosensitizer nanocomposite graphene oxide@TiO2@PS of graphene oxide.Prepared GO@TiO2@PS nanocomposite has preferably water-soluble, biological compatibility and low cytotoxicity, it can be used for tumor photo-thermal and light power synergistic treatment, in specific tumors or cancer cell, there is better fragmentation effect, show preferable application prospect.
Description
Technical field
The invention belongs to medical use optical dynamic therapy field of material technology, and in particular to a kind of graphene oxide alkene is modified
Photosensitizer nanocomposite and its application patent application matters.
Background technique
Photosensitizer is a kind of common medicament, for the treatment use for adapting to some specified diseases, needs to receive photosensitizer
Riceization load is to be prepared into Nano medication.Photosensitizer nanocrystallization technology is including organic in application, property according to nano-carrier
Two class of macromolecule carrier and inorganic carrier.Wherein nano oxidized titanium particle belongs to inorganic carrier, it has very big surface area
Than the volume with inner hole, duct is regular and size easily adjusts, and surfaces externally and internally is easy to modify, because of the controllability of its shapes and sizes
The advantages such as height, good water solubility, property stabilization, biofacies content height, it is often more important that, nano oxidized titanium particle is small to singlet oxygen etc.
Molecule has transmissibility, and singlet oxygen is the key factor in optical dynamic therapy.Therefore, nano oxidized titanium particle is that one kind can mention
The ideal nano-carrier of the photodynamic effect of high photosensitizer, is paid attention to by more and more researchers in recent years.
With regard to TiO2For@Photosan nanometric photosensitizer（Anticancer Effect of Photodynamic
Therapy with Photosan-Loaded Titanium Dioxide Nanoparticles on Panc-1
Pancreatic Cancer Cells In Vitro, Science of Advanced Materials, 2016,8 (5):
1145-1153）, due to being integrated with TiO2It the advantages of both nanostructure and organic photosensitizer Photosan, can be improved
The passive target performance and structural stability of Photosan, thus show in some cell experiments the killing to tumour cell
Effect.But actual application effect shows that titanium oxide wraps up Photosan nanometric photosensitizer（TiO2@Photosan）Water-soluble
Property, active targeting performance direction still have certain defect, thus still have certain distance with the expectation effect of actual medical application.
Graphene（Graphene, G）It is New Two Dimensional nano material most thin in the world, at first by graceful Chester university
Geim and Novoselov by micromechanical forces remove graphite successfully prepare and observed by one layer it is intensive, in honeycomb
Carbon atom in crystal lattice connects the monoatomic layer two-dimensional atomic crystal to be formed with sp2 hydridization.Since graphene is that have
Excellent electricity, mechanics and thermal property, therefore graphene has important answer in fields such as composite material, sensor, the energy
With prospect, become the hot spot of nm regime research in recent years.
In nano biological medical domain, the derivative graphene oxide of graphene（Graphene oxide, GO）, because its is huge
Big specific surface area, oxygen-containing group abundant（Hydroxyl, carboxyl, epoxy group etc.）It is easy to modify, thus has received widespread attention.
Graphene oxide（GO）The conjugate form of big pi bond can be formed with pi-pi accumulation power with Anthraquinones π ring structure anti-tumor drug,
It is adsorbed on graphene oxide, realizes drug delivery functions.On the other hand, graphene oxide（GO）Surface possesses a large amount of carboxylic
Acid, hydroxylate, epoxides π-π hydrophobic effect, can be built, ionic bond combination drug molecule by hydrogen；Simultaneously by covalent bond and
Non-covalent bond combines, and the hydrophilic radical that surface can be made to cover increases, to increase biocompatibility；Further more, graphene oxide
（GO）It surface can be in conjunction with targeting ligand or activation group for targeting transport.Based on these characteristics, graphene oxide is utilized
（GO）Nanosizing application is carried out to some drug molecules or modification has carried out more trial, but is modified for different molecular
Or nanosizing is in application, being limited to drug molecule or acting on target self-characteristic, final effect is often not consistent.
Summary of the invention
It is an object of that present invention to provide a kind of graphene oxides（GO）/ graphene（G）The nano combined material of modified photosensitizer
Material, so that material application foundation is established in the treatment for related disease.
Details are as follows for technical solution used by the application.
A kind of photosensitizer nanocomposite that graphene oxide/graphene is modified, is graphene oxide/graphene@bis-
Titanium oxide（TiO2）@photosensitizer Photosan, structural formula are expressed as：GO @TiO2@PS、G @TiO2@PS, is abbreviated as：G/ GO
@TiO2@ PS；
Wherein G indicates graphene（Graphene）；GO indicates graphene oxide（Graphene oxide）；PS indicates photosensitizer
（Photosan）, specific to be, for example,：It is a kind of in haematoporphyrin, hematoporphyrin derivative, hypocrellin, phthalocyanines photosensitizer etc.；
Using polyacrylic acid as dispersing agent when preparation, using ammonium hydroxide as catalyst, using hydrazine hydrate as reducing agent, specific preparation step is such as
Under：
（One）The titanium oxide nanoparticles of one step wet process preparation load photosensitizer Photosan；Specifically：
（1）By 0.1 ~ 0.3g polypropylene acid（PAA）After being dissolved into 4mL ammonium hydroxide, 1 ~ 4mg photosensitizer Photosan dissolution is added, often
The lower quickly stirring of temperature dissolves it sufficiently, forms solution A；
（2）Measure the butyl titanate of 0.5 ~ 1ml（TEOS）It is added in 2 ~ 3mL glacial acetic acid solution, slight concussion several times, is formed saturating
Bright solution B；
（3）Solution B is slowly at the uniform velocity added dropwise in solution A, the reaction was continued 4 after being added dropwise to complete ~ for 24 hours（It dropwise addition process and reacted
Journey solution should all carry out under blender stirring）；
It is centrifuged after the reaction was completed, cleaning precipitating, gained is that the TiOx nano of load Photosan is empty after vacuum freeze drying
Bulbus cordis particle TiO2@Photosan；
（Two）Prepare the modified photosensitizer nanocomposite graphene oxide@TiO of graphene oxide2@PS（GO @TiO2@
PS）, specifically：
（1）By step（One）In prepared TiO2@Photosan, which is dissolved in first in dimethyl sulfoxide, is made the molten of 1 ~ 10mmol/L
Liquid a；
（2）Take 2 ~ 12mg graphene oxide（GO）Be added in 100mL dehydrated alcohol, ultrasonic disperse and stir form clear solution
b；
（3）The phosphate buffer 80ml of 10mL solution a, 10mL solution b, pH=5.7 ~ 8.0 is taken, is uniformly mixed and forms mixed solution
C, reaction is overnight；
The unadsorbed excessive TiO on graphene oxide is removed with the centrifugation of 100 kDa screen pipes2@Photosan, and be washed with water
It washs until filtrate is hardly visible red（About 6 times）, it is freeze-dried to get GO@TiO2@Photosan nano combined
Grain；
Gained GO@TiO2@PS Nano composite granules can be directly used for the light light and heat power synergistic treatment of tumour；
（Three）Prepare the modified photosensitizer nanocomposite graphene@TiO of graphene2@Photosan（G @TiO2@PS）, tool
For body：
By step（2）Gained GO@TiO2@Photosan Nano composite granules are added to 0.25 ~ 0.5mL hydrazine hydrate solution, and (85% is dense
Degree, CR chemical reagent rank) in, it reacts 2 ~ 4 hours；
After reaction, it is centrifuged, cleans precipitating with ultrapure water no less than three times, be freeze-dried to get G@TiO2@PS is nano combined
Particle；
Gained G@TiO2@PS Nano composite granules can directly use the light light and heat power synergistic treatment of tumour.
In preparation process, graphene oxide can be prepared by the improved Hummers method of graphene；Specifically：
The reaction flask that 250 m L are assembled in ice-water bath, is added suitable concentrated sulfuric acid, is added with stirring 2g graphite powder and 1g
The solid mixture of sodium nitrate, then 6g potassium permanganate is added by several times, control reaction temperature is no more than 20 DEG C（15 ~ 20 DEG C or so）,
It is stirred to react 30min or so；
Then 35 DEG C or so are warming up to, continues stirring 30min and is slow added into a certain amount of deionized water, continue after mixing 20min,
And appropriate hydrogen peroxide is added and restores remaining oxidant, so that solution is become glassy yellow；
It filters, and is washed until sulfate radical-free is detected in filtrate with 5%HCl solution and deionized water while hot；Finally will
Filter cake, which is placed in 60 DEG C of vacuum oven, sufficiently to be dried, as graphene oxide.
In general, the major technique advantage of the application is embodied in following aspects：
（1）Titanium oxide itself is a kind of inorganic photosensitizer of burst of ultraviolel type, utilizes it as the carrier of organic photosensitizer, except advantageous
In improve outside organic photosensitizer physical chemistry defect inherently, two kinds of photosensitizers of organic/inorganic can also be integrated the advantages of,
The activation wave band of photosensitizer is expanded, curative effect is improved；It is using this feature, by being received using hollow titanium oxide in the application
Rice grain wraps up photosensitizer, to significantly improve drugloading rate, and further increases the bioavilability of photosensitizer；
（2）In early-stage study, inventor has found that graphene oxide can pass through functional carboxylic acid group（Directly and hydroxy combining）With
TiO2In conjunction with, thus it has been recognised by the inventors that can further improve TiO using this characteristic2@Photosan nanometric photosensitizer is in water
The defect of the aspect of performance such as dissolubility, active targeting, to be that application of the material in treating correlative diseases lays the foundation；Base
In this, in this application, by the package again using graphene/graphene oxide, the water of nano material is further improved
Dissolubility, and the photo-thermal effect of graphene is incorporated, thus with the dual function of photo-thermal and optical dynamic therapy, and pass through light
The synergistic effect of light and heat power, can further improve curative effect；
On the other hand, light induced electron-sky is realized using the electronic conduction ability that graphene/graphene oxide is excellent in the application
Cave efficiently separates, and improves the optical property of titanium dioxide, expands it and excites wave band, has established base to further increase curative effect
Plinth；
（3）Preliminary Applications experiments have shown that, nanomaterial product provided herein has the characteristics that toxicity is low, micro- in concentration 100
Low cytotoxicity is still maintained when grams per milliliter, thus with good application prospect；
On the other hand, application test shows compared to original TiO2@Photosan nanometric photosensitizer material, by graphene/
After graphene oxide modification, prepared G/GO@TiO2@Photosan nanocomposite have preferably it is water-soluble,
Biological compatibility and low cytotoxicity can be used for tumor photo-thermal and light power synergistic treatment, in specific tumors or cancer cell,
With better fragmentation effect, preferable application prospect is shown；The present invention is also the improvement and preparation of similar photosensitizer simultaneously
New technical thought is provided, thus there is preferable practicability and application.
Detailed description of the invention
Fig. 1 is the nano-titanium oxide transmission electron microscope to load Photosan（TEM）Figure；Shape measure shows to observe
Nano particle to preparation is in core-shell structure, and the smooth rule in surface, photosensitizer is wrapped in cavity, is formed nano combined photosensitive
Agent；
Fig. 2 is GO@TiO2The TEM of@Photosan nano particle schemes；
Fig. 3 is G@TiO2The TEM of@Photosan nano particle schemes；
Fig. 4 is 10mg/ml G@TiO2@PS、GO@TiO2@PS、TiO2@PS nanometric photosensitizer aqueous solution is 1.5W/cm in power2
980nm laser irradiation under photo-thermal effect curve graph；
Fig. 5 is G@TiO2@PS nanometric photosensitizer, PS nanometers, common PS（It is 0,25,50,75,100 that each group, which ultimately forms concentration,
ECA-109 cell CCK-8 ability of cell proliferation testing result is influenced with 200 μ g/ml:In ECA-109 cell culture medium
The said medicine of above-mentioned different proportion is added, after cultivating 48h, ability of cell proliferation is detected using CCK8 method（Select OD at 450nm
Value represents）；
Fig. 6 be the G@TiO2@PS nanometric photosensitizer of 100 μ g/ml, GO@TiO2@PS nanometric photosensitizer, PS nanometers, it is PS pairs common
The bis- dye methods of ECA-109 cell Annexin V and PI, which survey apoptosis of tumor cells testing result, to be influenced.
Specific embodiment
Explanation is further explained to the application below with reference to embodiment, before introducing specific embodiment, with regard to following realities
It applies the basic conditions such as involved part biological material, experiment reagent, laboratory apparatus in example and briefly introduces and be described as follows.
Biomaterial：
Human esophagus cancer Eca109 cell strain is purchased from Beijing consonance cell bank；
Experiment reagent：
Crystalline flake graphite (325 mesh of XF 010-1) alkene, first rich nanometer；
Photosensitizer Photosan (a kind of haematoporphyrin oligomer mixture), German Diolitec.
Embodiment 1
The modified photosensitizer nanocomposite graphene@TiO of the provided graphene of the present embodiment2@Photosan, structural formula
For G@TiO2@Photosan, G represent graphene；Using polyacrylic acid as dispersing agent when preparation, using ammonium hydroxide as catalyst, with hydration
Hydrazine is reducing agent, and specific preparation process is described as follows.
（One）The titanium oxide nanoparticles of one step wet process preparation load Photosan；Specifically：
（1）By 0.165 g polypropylene acid（PAA）After being dissolved into 4mL ammonium hydroxide, 1mg photosensitizer Photosan dissolution, room temperature is added
Lower quickly stirring dissolves it sufficiently, forms solution A；
（2）Measure the butyl titanate of 0.5 ml（TEOS）It is added in 2mL glacial acetic acid solution, slight concussion several times, is formed transparent
Solution B；
（3）Solution B is slowly at the uniform velocity added dropwise in solution A, the reaction was continued after being added dropwise to complete for 24 hours（Dropwise addition process and reaction process
Solution should all carry out under blender stirring）；
It is centrifuged after the reaction was completed, cleaning precipitating, gained is that the TiOx nano of load Photosan is empty after vacuum freeze drying
Bulbus cordis particle TiO2@Photosan。
To prepared TiOx nano hollow spheres TiO2@Photosan is scanned Electronic Speculum observation, as a result such as Fig. 1 institute
Show.As can be seen that its diameter of prepared nano-hollow ball particle is distributed between 80-1000nm, average diameter is about for analysis
120nm, size is nano-scale rank, thus can be recycled in capillary without will form embolism.
（Two）Prepare the modified photosensitizer nanocomposite graphene oxide@TiO of graphene oxide2@Photosan（GO
@TiO2@Photosan, GO represent graphene oxide）, specifically：
（1）By step（One）In prepared TiO2@Photosan is dissolved in the solution that 1 mmol/L is made in dimethyl sulfoxide first
a；
（2）Take 2 mg graphene oxides（GO）Be added in 100mL dehydrated alcohol, ultrasonic disperse and stir form clear solution b；
（3）The phosphate buffer 80ml of 10mL solution a, 10mL solution b, pH=5.7 is taken, is uniformly mixed and forms mixed solution C, instead
It should stay overnight；
The unadsorbed excessive TiO on graphene oxide is removed with the centrifugation of 100 kDa screen pipes2@Photosan, and be washed with water
It washs until filtrate is hardly visible red（About 6 times）, it is freeze-dried to get GO@TiO2@Photosan nano combined
Grain.
To gained GO@TiO2@Photosan Nano composite granules are scanned Electronic Speculum observation, as a result as shown in Figure 2.Analysis
As can be seen that its diameter is distributed between 80-1000nm, average diameter is about 120nm, still falls within nano-scale rank.
（Three）Prepare the modified photosensitizer nanocomposite graphene@TiO of graphene2@Photosan（G @TiO2@
Photosan）, specifically：
By step（2）Gained GO@TiO2@Photosan Nano composite granules are added to 0.25 mL hydrazine hydrate solution (85%, CR
Grade) in, it reacts 2 ~ 4 hours；
After reaction, it is centrifuged, cleans precipitating with ultrapure water no less than three times, be freeze-dried to get G@TiO2@Photosan receives
Rice composite particles；
To gained G@TiO2@Photosan Nano composite granules are scanned Electronic Speculum observation, as a result as shown in Figure 3.Analysis can be with
Find out, diameter is distributed between 80-1000nm, and average diameter is about 120nm, still falls within nano-scale rank.
To sum up result can be seen that using graphene/graphene oxide to TiO2@Photosan material carries out package modification
When, significant change does not occur for material overall dimension rank, thus can establish good basis for subsequent practical application.
It should be noted that graphene oxide is obtained by the improved Hummers method preparation of graphene in preparation process
?；Specifically：
The reaction flask that 250 m L are assembled in ice-water bath, is added suitable concentrated sulfuric acid, is added with stirring 2g graphite powder and 1g
The solid mixture of sodium nitrate, then 6g potassium permanganate is added by several times, control reaction temperature is no more than 20 DEG C（15 ~ 20 DEG C or so）,
It is stirred to react 30min or so；
Then 35 DEG C or so are warming up to, continues stirring 30min and is slow added into a certain amount of deionized water, continue after mixing 20min,
And appropriate hydrogen peroxide is added and restores remaining oxidant, so that solution is become glassy yellow；
It filters, and is washed until sulfate radical-free is detected in filtrate with 5%HCl solution and deionized water while hot；Finally will
Filter cake, which is placed in 60 DEG C of vacuum oven, sufficiently to be dried, as graphene oxide.
Inspection example
For to prepared G@TiO2@Photosan nano ZnO and practical application effect have further understanding, inventor
Further progress photo-thermal effect, cytotoxicity and PDT（Optical dynamic therapy）The preliminary experiment for the treatment of is analyzed, and related experiment is brief
It is described below.
（1）Photo-thermal effect
By prepared G@TiO2@PS、GO@TiO2@PS、TiO2@PS nano material is scattered in ultrapure water, and preparation concentration is
The solution of 10mg/ml measures the photo-thermal effect of gained nano particle using infrared light thermal imaging system.When measurement, setting light source is strong
Degree is 2.5W/cm2, wavelength 980nm, irradiation distance 0.5cm, liquor capacity 1ml, irradiation time 5 minutes.As a result as schemed
Shown in 4.
From fig. 4, it can be seen that compared to pure water and TiO2@PS contains G@TiO2@Photosan and GO@TiO2@PS、
TiO2The aqueous solution of@PS nano material is showing apparent photo-thermal effect after irradiating in short-term, thus can control to be subsequent
Application is treated to lay the foundation.
（2）Cytotoxicity
Method of proliferating is surveyed using the Cell Counting Kit-8 of standard to be measured the vitro cytotoxicity of nano material.Tool
For body：
By G@TiO2@PS、GO@TiO2@PS, PS nano particle and PS particle ultrasonic disperse are configured in DMEM culture solution
Concentration is 1mg/ml；
By tumour cell (human esophagus cancer Eca109 cell) sowing after 96 orifice plates（5×103/ hole）, by nanoparticle suspension
Liquid is added to 96 orifice plates, and being finally respectively formed concentration is 0,25,50,100,150 and 200 μ g/ml, and liquor capacity is 100 microlitres；
After being incubated for 48 hours altogether, 10 microlitres of Kit-8 solution are added, continue to be incubated for 2 hours；Then at microplate reader measurement 450nm
Absorbance.As a result as shown in Figure 5.
CCK8（Cell Counting Kit-8）Cytotoxicity experiment is as the result is shown：G@TiO2@PS、GO@TiO2@PS group
（G@TiO2@PS-NSs and GO@TiO2@PS-NSs i.e. in figure）Under cell survival rate starts slightly when concentration is 50 μ g/mL
Drop is gradually decreased as drug dose increases, and two groups start to be proliferated significant decrease (P compared to control group in 100 μ g/ml<
0.05)。
（3）Photodynamic therapy（PDT）Effect
Using Annexin-V and the bis- dye methods of PI, PDT effect is carried out in such a way that flow cytometry is by detection Apoptosis
Evaluation, specifically：
By tumour cell（Human esophagus cancer Eca109 cell）Sowing is after 24 orifice plates（1×104/ hole）；
Nano granule suspension is added to 24 orifice plates (experimental method and step are with aforementioned cell toxicity test), is ultimately formed dense
Degree is 100 μ g/ml, and liquor capacity is 1 ml；
After being incubated for 24 hours altogether, pancreatin digestion, PBS is washed 3 times, and the Annexin V dyestuff of 5 μ L is added, is protected from light and continues to be incubated for
After 20min, 5 microlitres of PI dyestuffs are added before upper machine.
FCM analysis result is as shown in Figure 6.Data record shows：Blank control group, G@TiO2@PS-NSs, GO@
TiO2@PS-NSs, PS-NSs, Free-PS group apoptosis rate be respectively (2.39% ± 0.86%), (32.89% ± 4.02%),
(38.53% ± 4.89%), (9.91% ± 3.18%), (8.88% ± 2.58%)；Comparison as can be seen that G@TiO2@PS-NSs,
GO@TiO2@PS-NSs is compared with blank control group, the statistically significant (P of apoptosis rate difference>0.05)., that is, passing through
After graphene or graphene oxide modification, hence it is evident that improve the application effect of photosensitizer.
Claims (10)
1. a kind of modified photosensitizer nanocomposite of graphene oxide, which is characterized in that the material is graphene oxide@bis-
Titanium oxide@photosensitizer, structural formula are expressed as：GO @TiO2@PS；Wherein GO indicates graphene oxide；PS indicates photosensitizer
Photosan；
Using polyacrylic acid as dispersing agent when prepared by the material, using ammonium hydroxide as catalyst, using hydrazine hydrate as reducing agent, especially by such as
Lower step prepares：
（One）The titanium oxide nanoparticles of one step wet process preparation load Photosan；Specifically：
（1）After polypropylene acid dissolution to ammonium hydroxide, photosensitizer Photosan dissolution is added, forms solution A；
（2）Butyl titanate is added in glacial acetic acid solution, clear solution B is formed；
（3）Solution B is added dropwise in solution A, continues sufficiently reaction after being added dropwise to complete；
It is centrifuged after the reaction was completed, cleaning precipitating, gained is the TiOx nano hollow spheres for loading Photosan after drying
TiO2@Photosan；
（Two）Prepare the modified photosensitizer nanocomposite graphene oxide@TiO of graphene oxide2@Photosan, it is specific and
Speech：
（1）By step（One）In prepared TiO2Solution a is made in@Photosan dissolution；
（2）It adds graphene oxide into dehydrated alcohol, dispersion forms clear solution b；
（3）It by solution a, solution b, phosphate buffer, is uniformly mixed and forms mixed solution C, reaction is overnight；
Remove the unadsorbed excessive TiO on graphene oxide2@Photosan, washing, drying are to get GO@TiO2PS nanometers of@multiple
Close particle.
2. the modified photosensitizer nanocomposite of graphene oxide as described in claim 1, which is characterized in that step（Two）
In, the graphene oxide is prepared by the improved Hummers method of graphene.
3. the modified photosensitizer nanocomposite of graphene oxide as described in claim 1, which is characterized in that step（One）'s
Step（1）In, material amounts are：0.1 ~ 0.3g polypropylene acid, 4mL ammonium hydroxide, 1 ~ 4mg photosensitizer Photosan；
Step（One）The step of（2）In, material amounts are：The butyl titanate of 0.5 ~ 1ml, 2 ~ 3mL glacial acetic acid.
4. the modified photosensitizer nanocomposite of graphene oxide as described in claim 1/graphene, which is characterized in that step
Suddenly（Two）The step of（1）In, TiO is dissolved using dimethyl sulfoxide2TiO in@Photosan, solution a2@Photosan concentration be 1 ~
10mmol/L；
Step（Two）The step of（2）In, material amounts are 2 ~ 12mg graphene oxide, 100mL dehydrated alcohol.
5. the modified photosensitizer nanocomposite of graphene oxide as described in claim 1/graphene, which is characterized in that institute
Stating photosensitizer Photosan is specially：It is haematoporphyrin, hematoporphyrin derivative, hypocrellin, a kind of in phthalocyanines photosensitizer.
6. the preparation method of the modified photosensitizer nanocomposite of any one of claim 1 ~ 5 graphene oxide, special
Sign is that specific packet can following steps：
（One）The titanium oxide nanoparticles of one step wet process preparation load Photosan；Specifically：
（1）After polypropylene acid dissolution to ammonium hydroxide, photosensitizer Photosan dissolution is added, forms solution A；
（2）Butyl titanate is added in glacial acetic acid solution, clear solution B is formed；
（3）Solution B is added dropwise in solution A, continues sufficiently reaction after being added dropwise to complete；
It is centrifuged after the reaction was completed, cleaning precipitating, gained is the TiOx nano hollow spheres for loading Photosan after drying
TiO2@Photosan；
（Two）Prepare the modified photosensitizer nanocomposite graphene oxide@TiO of graphene oxide2@Photosan, it is specific and
Speech：
（1）By step（One）In prepared TiO2Solution a is made in@Photosan dissolution；
（2）It adds graphene oxide into dehydrated alcohol, dispersion forms clear solution b；
（3）It by solution a, solution b, phosphate buffer, is uniformly mixed and forms mixed solution C, reaction is overnight；
Remove the unadsorbed excessive TiO on graphene oxide2@Photosan, washing, drying are to get GO@TiO2PS nanometers of@multiple
Close particle.
7. the modified photosensitizer nanocomposite of any one of claim 1 ~ 5 graphene oxide is in preparing oncology pharmacy
Application, which is characterized in that be adapted to photodynamic therapy application.
8. the modified photosensitizer nanocomposite of graphene oxide as claimed in claim 7 is preparing answering in oncology pharmacy
With, which is characterized in that the tumour is tumour caused by human Eca109 cell line.
9. the modified photosensitizer nanocomposite of graphene oxide as claimed in claim 8 is preparing answering in oncology pharmacy
With, which is characterized in that when being used for human esophagus cancer Eca109 cell, the modified photosensitizer nanocomposite of graphene oxide is dense
Degree is no more than 200 μ g/ml.
10. the modified photosensitizer nanocomposite of graphene oxide as claimed in claim 9 is preparing answering in oncology pharmacy
With, which is characterized in that when being used for human esophagus cancer Eca109 cell, the modified photosensitizer nanocomposite of graphene oxide is dense
Degree is 100 μ g/ml.
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