CN108187047A - Nano-titanium photo-thermal preparation and its preparation method and application - Google Patents
Nano-titanium photo-thermal preparation and its preparation method and application Download PDFInfo
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Abstract
The present invention provides a kind of nano-titanium photo-thermal preparation, including two-dimentional titanium nanometer sheet and the biocompatible materials for being coated on two-dimentional titanium nanometer sheet surface.Nano-titanium photo-thermal preparation provided by the invention, photothermal conversion efficiency is high, good biocompatibility, safe and non-toxic, available for the photo-thermal therapy including tumour.The present invention also provides a kind of preparation method of nano-titanium photo-thermal preparation, including:Titanium material is provided, the titanium material is removed using the method that liquid phase is removed, obtains two-dimentional titanium nanometer sheet;Biocompatible materials are provided, two-dimentional titanium nanometer sheet and biocompatible materials at 10 30 DEG C are mixed into 3 6h, obtain nano-titanium photo-thermal preparation.The present invention also provides a kind of preparation method of nano-titanium photo-thermal preparation, preparation method is simple to operation.The present invention also provides a kind of application of nano-titanium photo-thermal preparation as described above in photo-thermal therapy drug is prepared.
Description
Technical field
The present invention relates to Nano biomedical material fields, and in particular to a kind of nano-titanium photo-thermal preparation and preparation method thereof
And application.
Background technology
At present, it for the treatment of cancer, except traditional operative treatment, radiation treatment and chemotherapy, and has developed
The novel therapies such as immunotherapy, cell therapy.But although current therapy can extend the life of patient to a certain extent
Life, still there is its limitation, such as side effect it is big, can not fully erased tumour cell, can not cure.Therefore, new treatment is developed
Method is still the hot spot of cancer field.
Near-infrared phototherapy based on nano material is a kind of novel, potential therapy, particularly near infrared light response
Photo-thermal therapy, solve light wave in short wavelengths' phototherapy such as ultraviolet light and visible ray easily absorbed, easily scattering, have nucleic acid poison
The problem of property and tissue penetration force difference.Near-infrared wavelength about between 700-1000 nanometers there is low absorption, height to wear
The advantages of permeability (1 centimetre or more).
Conventional photo-thermal therapy material mainly has gold nano grain, carbon nanotube and graphene etc. at present.It is but existing
Optothermal material can not often take into account photothermal conversion efficiency and biocompatibility.
Therefore, it there is an urgent need for finding a kind of photothermal conversion efficiency height, good biocompatibility, safe and non-toxic optothermal material, is used for
Photo-thermal therapy including tumour.
Invention content
To solve the above problems, the present invention provides a kind of photothermal conversion efficiency height, good biocompatibility, it is safe and non-toxic
Nano-titanium photo-thermal preparation.
First aspect present invention provides a kind of nano-titanium photo-thermal preparation, including two-dimentional titanium nanometer sheet and is coated on described two
Tie up the biocompatible materials on titanium nanometer sheet surface.
Wherein, the mass ratio of the two-dimentional titanium nanometer sheet and the biocompatible materials is 1:1-10.
Wherein, the mass ratio of the two-dimentional titanium nanometer sheet and the biocompatible materials is 1:1.
Wherein, the thickness of the two-dimentional titanium nanometer sheet is 1-50nm.
Wherein, the length and width dimensions of the two-dimentional titanium nanometer sheet are 10-50nm.
Wherein, the biocompatible materials include hyaluronic acid, glucan and its derivative, chitosan and its derivative
Object, pectin, carboxymethyl cellulose, albumin, liposome, cell membrane, polyvinylpyrrolidone, poly lactic-co-glycolic acid copolymerization
It is one or more in object, polyethyleneimine, polyacrylic acid and polyethylene glycol and its derivative.
Wherein, the biocompatible materials are polyethylene glycol and its derivative, the polyethylene glycol and its derivative
Molecular weight is 200-20000.
The nano-titanium photo-thermal preparation that first aspect present invention provides, photothermal conversion efficiency is higher, biocompatibility is good, peace
Atoxic, available for the photo-thermal therapy including tumour.
Second aspect of the present invention provides a kind of preparation method of nano-titanium photo-thermal preparation, including:
Titanium material is provided, the titanium material is removed using the method that liquid phase is removed, obtains two-dimentional titanium nanometer sheet;
Biocompatible materials are provided, the two-dimentional titanium nanometer sheet and biocompatible materials are mixed at 10-30 DEG C
3-6h is stirred, obtains nano-titanium photo-thermal preparation.
Wherein, the method for the liquid phase stripping specifically includes following operation:
The titanium material is added in into solvent, Probe Ultrasonic Searching 8-15h is used under ice bath environment;The Probe Ultrasonic Searching knot
Shu Hou continues using water bath sonicator, and the water bath sonicator time is 3-10h, and the temperature of the water-bath is kept for 5-15 DEG C;Ultrasound
Afterwards, centrifuged and be dried to obtain two-dimentional titanium nanometer sheet.
Second aspect of the present invention provides a kind of preparation method of nano-titanium photo-thermal preparation, and preparation method is simple to operation,
Nano-titanium photo-thermal preparation photothermal conversion efficiency obtained is high, good biocompatibility.
Third aspect present invention provides nano-titanium photo-thermal preparation as described above in photo-thermal therapy drug is prepared
Using.
To sum up, advantageous effect of the present invention includes the following aspects:
1st, nano-titanium photo-thermal preparation provided by the invention, photothermal conversion efficiency is high, good biocompatibility, safe and non-toxic, can
For the photo-thermal therapy including tumour;
2nd, the preparation method of nano-titanium photo-thermal preparation provided by the invention, method are simple to operation.
Description of the drawings
Fig. 1 is the transmission electron microscope picture of two-dimentional titanium nanometer sheet made from embodiment 1;
Fig. 2 is the atomic force microscope picture of two-dimentional titanium nanometer sheet made from embodiment 1;
Fig. 3 is the abosrption spectrogram of the liquid phase stripping process of two-dimentional titanium nanometer sheet in embodiment 1;
Fig. 4 is the two-dimentional titanium nanometer sheet aqueous dispersions photo of various concentration;
Fig. 5 is the abosrption spectrogram of the two-dimentional titanium nanometer sheet aqueous dispersions of various concentration;
Fig. 6 is the extinction coefficient of two-dimentional titanium nanometer sheet aqueous dispersions;
Fig. 7 is the heating curve of the two-dimentional titanium nanometer sheet aqueous dispersions of various concentration;
Fig. 8 is the photothermal conversion efficiency of two-dimentional titanium nanometer sheet aqueous dispersions;
Fig. 9 is the cytotoxicity assay result figure of two-dimentional titanium nanometer sheet;
Figure 10 is influence of the two-dimentional titanium nanometer sheet to mouse weight;
Figure 11 is two-dimentional titanium nanometer sheet on causing mouse tissue organ damage influence figure;
Figure 12 is that the two-dimentional titanium nanometer sheet of various concentration kills ability design sketch to the photo-thermal of cell;
Figure 13 is that the two-dimentional titanium nanometer sheet that the PEG2000 of 50ppm concentration is coated kills cell under different light application times
Hinder the measure of ability;
The variation of tumor locus temperature when Figure 14 is mouse tumor photo-thermal therapy;
The curve of tumor locus temperature change when Figure 15 is mouse tumor photo-thermal therapy;
Figure 16 is the volume change that tumor-bearing mice receives tumour after photo-thermal therapy.
Specific embodiment
As described below is the preferred embodiment of the present invention, it is noted that for those skilled in the art
For, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also considered as
Protection scope of the present invention.
" two-dimentional titanium nanometer sheet ", " titanium nano particle " or " titanium " that the present invention mentions, except specified otherwise, refer to simple substance
Titanium.
First aspect present invention provides a kind of nano-titanium photo-thermal preparation, including two-dimentional titanium nanometer sheet and is coated on described two
Tie up the biocompatible materials on titanium nanometer sheet surface.
In embodiment of the present invention, the thickness of the two dimension titanium nanometer sheet is 1-50nm.Optionally, the two-dimentional titanium nanometer
The thickness of piece is 3-5nm.Optionally, the thickness of the two-dimentional titanium nanometer sheet is 5-10nm.Optionally, the two-dimentional titanium nanometer sheet
Thickness be 10-50nm.Still optionally further, the thickness of the two-dimentional titanium nanometer sheet be 1nm, 5nm, 10nm, 15nm, 20nm,
25nm, 30nm, 35nm, 40nm, 45nm or 50nm.
In embodiment of the present invention, the length and width dimensions of the two dimension titanium nanometer sheet are 10-50nm.Optionally, the two dimension
The length and width dimensions of titanium nanometer sheet are 30-40nm.Optionally, the length and width dimensions of the two-dimentional titanium nanometer sheet are 10-30nm.Further
Optionally, the length and width dimensions of the two-dimentional titanium nanometer sheet for 10nm, 15nm, 20nm, 25nm, 30nm, 35nm, 40nm, 45nm or
50nm。
In embodiment of the present invention, the mass ratio of the two dimension titanium nanometer sheet and the biocompatible materials is 1:1-
10.Optionally, the mass ratio of the two-dimentional titanium nanometer sheet and the biocompatible materials is 1:1、1:2、1:3、1:4、1:5、
1:6、1:7、1:8、1:9 or 1:10.
In embodiment of the present invention, the two dimension titanium nanometer sheet has the absorption from visible region to near-infrared region.It can
Selection of land, the light absorption wavelength ranging from 200-2000nm of the two dimension titanium nanometer sheet.
In embodiment of the present invention, the photothermal conversion efficiency of the two dimension titanium nanometer sheet is more than or equal to 70%.
The two-dimentional titanium nanometer sheet that first aspect present invention provides has the strong suction of environmental-friendly, bio-compatibility, full spectrum
The advantages that receipts and higher photothermal conversion efficiency, has excellent light thermal property.
In embodiment of the present invention, the biocompatible materials include hyaluronic acid, glucan and its derivative, shell gathers
Carbohydrates and their derivative, pectin, carboxymethyl cellulose, albumin, liposome, cell membrane, polyvinylpyrrolidone, polylactic acid-glycolic
It is one or more in acetic acid copolymer, polyethyleneimine, polyacrylic acid and polyethylene glycol and its derivative.It is further optional
Ground, the biocompatible materials include polyethylene glycol and its derivative, Poly(D,L-lactide-co-glycolide, albumin, lipid
At least one of body and cell membrane.Still optionally further, the biocompatible materials include polyethylene glycol and its derivative,
The molecular weight of the polyethylene glycol and its derivative is between 200-20000.Optionally, the end of the polyethylene glycol can be by
It is amido modified.Optionally, the biocompatible materials are adsorbed by electrostatic interaction on the surface of the two-dimentional titanium nanometer sheet.
In embodiment of the present invention, the nano-titanium photo-thermal preparation further includes targeting material, targeting the passing through of material
Key connection is learned in the two-dimentional titanium nanometer sheet or is connected on the biocompatible materials.Optionally, the targeting material is
Folic acid, the folic acid are connected to by amido bond on the polyethylene glycol.
In embodiment of the present invention, the nano-titanium photo-thermal preparation can be dispersed in physiological saline, phosphate buffer or
Subsequent applications are used in deionized water.
The nano-titanium photo-thermal preparation that first aspect present invention provides, photothermal conversion efficiency is high, good biocompatibility, safe nothing
Poison, available for the photo-thermal therapy including tumour.
Second aspect of the present invention provides a kind of preparation method of nano-titanium photo-thermal preparation, including:
Titanium material is provided, the titanium material is removed using the method that liquid phase is removed, obtains two-dimentional titanium nanometer sheet;
Biocompatible materials are provided, by the two-dimentional titanium nanometer sheet and the biocompatible materials at 10-30 DEG C
3-6h is mixed, obtains nano-titanium photo-thermal preparation.
In embodiment of the present invention, two-dimentional titanium nanometer sheet and biocompatible materials are mixed into 3-6h at 25 DEG C.
In embodiment of the present invention, the specific preparation method of the nano-titanium photo-thermal preparation includes:By biocompatibility material
After material is dissolved in suitable first solvent, biocompatible materials solution is obtained, two-dimentional titanium nanometer sheet is scattered in suitable the
In two solvents, two-dimentional titanium nanometer sheet dispersion liquid is obtained, by the biocompatible materials solution and the two-dimentional titanium nanometer sheet point
Dispersion liquid stirs 3-6h after being mixed at 10-30 DEG C, obtains nano-titanium photo-thermal preparation.
Optionally, first solvent is the solvent that can dissolve biocompatible materials, such as works as biocompatible materials
During for polyethylene glycol, the first solvent can select deionized water.
Optionally, second solvent includes deionized water.
In embodiment of the present invention, the stir speed (S.S.) turns/min for 100 turns/min-700.
In embodiment of the present invention, after stirring, after gained mixture centrifugal drying, biocompatible materials cladding is obtained
Two-dimentional titanium nanometer sheet to get nano-titanium photo-thermal preparation.
In embodiment of the present invention, the method for the liquid phase stripping specifically includes following operation:
The titanium material is added in into solvent, Probe Ultrasonic Searching 8-15h is used under ice bath environment;The Probe Ultrasonic Searching knot
Shu Hou continues using water bath sonicator, and the water bath sonicator time is 3-10h, and bath temperature is kept for 5-15 DEG C;After ultrasound, carry out
Centrifuge and be dried to obtain two-dimentional titanium nanometer sheet.
Optionally, the solvent includes at least one of isopropanol, ethyl alcohol, water and methyl pyrrolidone.
Optionally, a concentration of 1-7mg/mL of the titanium material in the solvent.
Optionally, the power of the Probe Ultrasonic Searching is 200-250W.Still optionally further, the power of the Probe Ultrasonic Searching is
240W。
Optionally, the time of the Probe Ultrasonic Searching is 10h.
Optionally, the Probe Ultrasonic Searching is non-continuous ultrasound, and it is 2/4s to select the ultrasonic ON/OFF time, i.e., first ultrasound 2s, so
Ultrasonic probe is closed afterwards and keeps 4s, is continuing ultrasound 2s, and so on.
Optionally, the water bath sonicator power is 300-380W.Still optionally further, the water bath sonicator power is
360W。
Optionally, the time of the water bath sonicator is 8h.
Optionally, the bath temperature is kept for 10 DEG C.
Optionally, it after ultrasound, is centrifuged, the operation of the centrifugation includes:The centrifugal force of 1800-2200g is used first,
20-35min is centrifuged, takes supernatant;Then the supernatant is continued to centrifuge using the centrifugal force of 10000-13000g, is sunk
It is two-dimentional titanium nanometer sheet to form sediment.Still optionally further, 30min is centrifuged, takes supernatant using the centrifugal force of 2000g first;Then
The supernatant is continued to centrifuge using the centrifugal force of 12000g, is precipitated, will be received after gained precipitation drying up to two-dimentional titanium
Rice piece.Optionally, the mode of the drying is unlimited, may be, for example, vacuum drying.
Prior art generally use liquid phase stripping method is used for removing two-dimensional layer material.And the present invention is shelled for the first time using liquid phase
The non-laminar metal material of two dimension is removed, and successful from method.
Second aspect of the present invention provides a kind of preparation method of nano-titanium photo-thermal preparation, and preparation method is simple to operation,
Nano-titanium photo-thermal preparation photothermal conversion efficiency obtained is higher, biocompatibility is good.
The embodiment of the present invention third aspect provides a kind of nano-titanium photo-thermal preparation as described above and is preparing photo-thermal
Application in medicine.
Embodiment 1:
A kind of preparation method of nano-titanium photo-thermal preparation, including:
(1) two-dimentional titanium nanometer sheet is prepared;
The titanium valve of 500mg is added in the isopropanol of 100ml.Then selection Probe Ultrasonic Searching 240W, ultrasonic 10h.Selection is super
The sound ON/OFF time is 2/4s, and is that ultrasound is carried out under ice bath environment.After Probe Ultrasonic Searching is complete, then using water bath sonicator.Water
Bath ultrasonic power is 360W.Ultrasonic time is 8h.Bath temperature is kept for 10 DEG C.
The metal simple-substance titanium nanometer sheet that ultrasound is needed later using the method for centrifugation.The centrifugation of 2000g is used first
Power centrifuges 30min.Supernatant is taken, then continues to centrifuge using 12000g by supernatant, be precipitated.The precipitation, after vacuum drying i.e.
Obtain two-dimentional titanium nanometer sheet.
(2) PEG2000 solution is provided, titanium nanometer sheet two-dimentional made from step (1) is dispersed in suitable quantity of water and obtains two dimension
Titanium nanometer sheet dispersion liquid mixes two-dimentional titanium nanometer sheet dispersion liquid with PEG2000 solution, wherein, two-dimentional titanium nanometer sheet with
The mass ratio of PEG2000 is 1:1, it is mixed 5h at 25 DEG C, after centrifugal drying, the two-dimentional titanium for obtaining PEG2000 claddings is received
Rice piece is up to nano-titanium photo-thermal preparation.
As shown in FIG. 1, FIG. 1 is the Electronic Speculum shape appearance figures of titanium nanometer sheet two-dimentional made from step (1).Its size is less than 50nm.
Atomic force microscope picture is shown in Fig. 2.As seen from the figure, the thickness of two-dimentional titanium nanometer sheet is in 3nm or so.Therefore by saturating
The observation of radio mirror and atomic force microscope can separate two-dimensional metallic simple substance titanium nanometer sheet by liquid phase stripping method really.
As shown in Figure 3a, it is respectively removed in isopropanol (IPA) and water, the absorption of the two-dimentional titanium nanometer sheet of same concentrations
Spectrum.It is obvious that the absorption spectrum of two-dimentional titanium nanometer sheet removed in IPA has the slope of higher absorption value and bigger (i.e.
A curve above in Fig. 3 a).This illustrates fully remove bigger titanium particle into smaller titanium nanometer in IPA
Piece.Further, the absorption of the different splitting times (referring to the water bath sonicator time) of the metal simple-substance titanium of same concentrations is compared
Value (as shown in Figure 3b), finds the increase with splitting time, and absorption spectrum is being continuously increased, and will appear saturation
State.
Embodiment 2:
A kind of preparation method of nano-titanium photo-thermal preparation, including:
(1) two-dimentional titanium nanometer sheet is prepared;
The titanium valve of 500mg is added in the isopropanol of 100ml.Then selection Probe Ultrasonic Searching 200W, ultrasonic 15h.Selection is super
The sound ON/OFF time is 2/4s, and is that ultrasound is carried out under ice bath environment.After Probe Ultrasonic Searching is complete, then using water bath sonicator.Water
Bath ultrasonic power is 300W.Ultrasonic time is 10h.Bath temperature is kept for 15 DEG C;
The metal simple-substance titanium nanometer sheet that ultrasound is needed later using the method for centrifugation.The centrifugation of 1800g is used first
Power centrifuges 35min.Supernatant is taken, then continues to centrifuge using 10000g by supernatant, be precipitated, up to two dimension after vacuum drying
Titanium nanometer sheet.
(2) PEG2000 solution is provided, titanium nanometer sheet two-dimentional made from step (1) is dispersed in suitable quantity of water and obtains two dimension
Titanium nanometer sheet dispersion liquid mixes two-dimentional titanium nanometer sheet dispersion liquid with PEG2000 solution, wherein, two-dimentional titanium nanometer sheet with
The mass ratio of PEG2000 is 1:10, it is mixed 3h at 30 DEG C, after centrifugal drying, the two-dimentional titanium for obtaining PEG2000 claddings is received
Rice piece is up to nano-titanium photo-thermal preparation.
Embodiment 3:
A kind of preparation method of nano-titanium photo-thermal preparation, including:
(1) two-dimentional titanium nanometer sheet is prepared;
The titanium valve of 500mg is added in the isopropanol of 100ml.Then selection Probe Ultrasonic Searching 250W, ultrasonic 8h.Selection ultrasound
The ON/OFF time is 2/4s, and is that ultrasound is carried out under ice bath environment.After Probe Ultrasonic Searching is complete, then using water bath sonicator.Water-bath
Ultrasonic power is 380W.Ultrasonic time is 3h.Bath temperature is kept for 5 DEG C;
The metal simple-substance titanium nanometer sheet that ultrasound is needed later using the method for centrifugation.The centrifugation of 2200g is used first
Power centrifuges 20min.Supernatant is taken, then continues to centrifuge using 13000g by supernatant, be precipitated, up to two dimension after vacuum drying
Titanium nanometer sheet.
(2) PEG2000 solution is provided, titanium nanometer sheet two-dimentional made from step (1) is dispersed in suitable quantity of water and obtains two dimension
Titanium nanometer sheet dispersion liquid mixes two-dimentional titanium nanometer sheet dispersion liquid with PEG2000 solution, wherein, two-dimentional titanium nanometer sheet with
The mass ratio of PEG2000 is 1:5, it is mixed 6h at 10 DEG C, after centrifugal drying, the two-dimentional titanium for obtaining PEG2000 claddings is received
Rice piece is up to nano-titanium photo-thermal preparation.
Effect example
(1) test of absorption spectrum and light thermal property
Prepare the two-dimentional titanium nanometer sheet aqueous dispersions absorbance spectrum and light thermal property of various concentration.Absorption spectrum uses
Ultraviolet-spectrophotometer measurement.Photo-thermal experiment is using 808nm laser.The two-dimentional titanium for preparing 10,25,50 and 100ppm respectively is received
Rice piece aqueous dispersions (as shown in Figure 4).The aqueous dispersions of preparation are respectively charged into quartz colorimetric utensil, are put into uv-spectrophotometric
Trap is measured in meter card slot.The absorption curve of various concentration is as shown in Figure 5.Two dimension can be obtained according to the absorption at 808nm
The extinction coefficient of titanium nanometer sheet is 20.8Lg-1cm-1(as shown in Figure 6).The value is higher than black phosphorus (14.8Lg-1cm-1).For photo-thermal
The measurement of experiment is taken 1ml two dimension titanium nanometer sheets aqueous dispersions to add in cuvette, is irradiated using 808nm laser, and simultaneously
Temperature curve is recorded with thermocouple.The temperature of various concentration is shown with the heating figure of laser irradiation time in Fig. 7.By quantitative
Calculating, can obtain two-dimentional titanium nanometer sheet photothermal conversion efficiency be 73.4% (as shown in Figure 8).
The photothermal conversion efficiency (73.4%) of the two-dimentional titanium nanometer sheet of present invention highest in the light thermit powder being had been reported that is high
In the emerging two-dimentional light thermit powder of traditional gold nano grain (21%), including MoS2(24.4%) black phosphorus quantum dot (28.4%)
Ti3C2Nanometer sheet (30.6%) and tellurium quantum dot (45.5%), therefore, two-dimentional titanium nanometer sheet photothermal conversion efficiency value are apparently higher than
Other light thermit powders currently studied.Therefore, two-dimentional titanium nanometer sheet light thermal property produced by the present invention is good.
(2) parameter in bio kinetic model of two-dimentional titanium nanometer sheet
The two-dimentional titanium nanometer sheet of different quality is scattered in cell culture medium, then be incubated altogether, then measure from different cells
The vigor of cell.A.1 hepatocellular carcinoma cells SMMC-7721, melanoma cells B16 and macrophage J774 are distinguished first
It is taped against in 96 orifice plates, after cell is adherent, prepares to test.0,10,25,50 is prepared respectively with DMEM high glucose mediums,
The two-dimentional titanium nanometer sheet dispersion liquid of 100ppm concentration takes 100 μ l dispersion liquids, replaces the culture medium in aforementioned 96 orifice plate, is being incubated
After 24 hours, the vigor of cell inside each hole of CCK8 kit measurements, 3 parallel holes of each group of experimental setup are used.Such as
Shown in Fig. 9, in various kinds of cell, with the raising (from 0 to 100ppm) of two-dimentional titanium nanometer sheet concentration and the reality of non-plus nano piece
A group comparison is tested, cell viability has no apparent decline.This illustrates that two-dimentional titanium nanometer sheet does not have apparent cytotoxicity.
The embodiment of the present invention also has detected the toxicity of two-dimentional titanium nanometer sheet in model animal.Respectively by two-dimentional titanium nanometer sheet
Physiological saline is scattered in the two-dimentional titanium nanometer sheet of PEG2000 claddings, the dispersion liquid for obtaining 100ppm is spare.Take the female of 6 week old
Property Balb/c nude mices, are received the 100ppm two dimension titaniums of the physiological saline (control) of 100 μ l, 100 μ l by hypodermic mode
Rice piece (is represented in figure with " titanium nanometer sheet ") two-dimentional titanium nanometer sheet that the 100ppm PEG of dispersion liquid and 100 μ l coat (in figure with
" the titanium nanometer sheet of coated with polyethylene glycol " represent) dispersion liquid be injected into it is subcutaneous below mouse right fore.Respectively after injection
It measures the weight of mouse within 1st, 3,5,7,9,11,13,15 day, and put to death mouse at the 15th day, take its main organs heart
Liver and spleen lung kidney, carries out H&E dyeing, and whether observation nanometer sheet leads to mouse tissue organ damage.As shown in Figure 10, two-dimentional titanium nanometer
Piece does not interfere with the variation of its weight;As shown in figure 11, two-dimentional titanium nanometer sheet will not cause to damage to mouse tissue organ.
In conclusion two-dimentional titanium nanometer sheet under in vitro conditions to cancer cell, normal cell and in vivo under the conditions of all
There is no toxicity, it is shown that its biocompatibility and it is safe and non-toxic the advantages of.
(3) cellkilling capacity of two-dimentional titanium nanometer sheet photo-thermal effect measures
SMMC-7721, B16 and J774A.1 cell are laid on 96 orifice plates respectively, after cell is adherent, by various concentration
It is scattered in the two-dimentional titanium nanometer sheet and cell incubation of cell culture medium, two-dimentional a concentration of difference 0 of titanium nanometer sheet, 5,10,20,30,
50ppm, each experimental group set 3 parallel holes.After being incubated 2 hours, with the laser of 808nm, with 1W cm-2Power illumination 10
Minute, 24 hours after irradiation, with the vigor of CCK8 kit measurement cells.As shown in figure 12, the two-dimentional titanium of low concentration (5ppm)
The photo-thermal effect of nanometer sheet just has the cellkilling capacity of part, and under the conditions of 10ppm, highly significant is (right for killing ability
20% is can reach in cancer cell, 80%) macrophage can reach, in the concentration of more than 30ppm, the light of two-dimentional titanium nanometer sheet
Fuel factor can kill cell completely substantially.And PEG2000 claddings or uncoated two-dimentional its light of titanium nanometer sheet
Fuel factor killing ability is consistent.
Similarly, under conditions of 50ppm, the PEG2000 two-dimentional titanium nanometer sheets coated are incubated altogether with SMMC-7721 cells
It educates, then with 808nm, 1W cm-2Power irradiance, measure its killing under different light application times (0,2,5,8,10 minute)
Ability, as shown in figure 13, the only illumination of 2 minutes is just enough to kill all cells completely.
In conclusion the photo-thermal effect of two-dimentional titanium nanometer sheet can be used for cell killing, and low concentration, the short time it is near
With regard to good Cell killing efficacy can be reached under the conditions of infrared light, it is shown that its excellent photothermal conversion efficiency.
(4) the tumor thermal therapy effect measuring of two-dimentional titanium nanometer sheet photo-thermal effect
By 5 × 106SMMC-7721 cell subcutaneous injections are subcutaneous to female Balb/c nude mices, after about 10 days, tumour
Volume reaches 100-200mm3, using this liver cancer model as the object of two-dimentional titanium nanometer sheet photo-thermal therapy.By PEG2000 claddings
Two-dimentional titanium nanometer sheet is distributed in phosphate buffer, a concentration of 100ppm.During oncotherapy, 100 μ l nanometer sheets of intratumor injection
Dispersion liquid, then by mouse anesthesia, using the laser of 808 nano wave lengths, in 1Wcm-2Power under irradiation contain titanium nanometer sheet
Tumor locus 5 minutes, to carry out photo-thermal therapy to tumour.Figure 14 is to have recorded tumor locus temperature per minute with infrared detector
The situation of change of degree, Figure 15 are then the temperature variation curves of tumor locus in therapeutic process, the two captions are carrying out light
During heat cure, temperature raising is very quick caused by two-dimentional titanium nanometer sheet, and 20 DEG C can be increased in 1 minute.And at about 1 minute
Afterwards, temperature, which slowly rises, gradually keeps stablizing.Then, the 1st, 3,5,7,9,11,13,15 day after the treatment measures tumour respectively
Volume, as shown in figure 16, it is known that, tumor size reduces rapidly after photo-thermal therapy, the tumor group during entire treatment
It knits and is killed, tumour growth is inhibited, and achieves good therapeutic effect.
Therefore, the photo-thermal preparation comprising two-dimentional titanium nanometer sheet can be efficiently used for the photo-thermal therapy of tumour.
Embodiment described above only expresses the several embodiments of the present invention, and description is more specific and detailed, but simultaneously
Cannot the limitation to the scope of the claims of the present invention therefore be interpreted as.It should be pointed out that for those of ordinary skill in the art
For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to the guarantor of the present invention
Protect range.Therefore, the protection domain of patent of the present invention should be determined by the appended claims.
Claims (10)
1. a kind of nano-titanium photo-thermal preparation, which is characterized in that including two-dimentional titanium nanometer sheet and be coated on the two-dimentional titanium nanometer sheet
The biocompatible materials on surface.
2. nano-titanium photo-thermal preparation as described in claim 1, which is characterized in that the two dimension titanium nanometer sheet and the biofacies
The mass ratio of capacitive material is 1:1-10.
3. nano-titanium photo-thermal preparation as claimed in claim 2, which is characterized in that the two dimension titanium nanometer sheet and the biofacies
The mass ratio of capacitive material is 1:1.
4. nano-titanium photo-thermal preparation as described in claim 1, which is characterized in that the thickness of the two dimension titanium nanometer sheet is 1-
50nm。
5. nano-titanium photo-thermal preparation as described in claim 1, which is characterized in that the length and width dimensions of the two dimension titanium nanometer sheet are
10-50nm。
6. nano-titanium photo-thermal preparation as described in claim 1, which is characterized in that the biocompatible materials include hyalomitome
Acid, glucan and its derivative, chitosan and its derivative, pectin, carboxymethyl cellulose, albumin, liposome, cell membrane,
Polyvinylpyrrolidone, Poly(D,L-lactide-co-glycolide, polyethyleneimine, polyacrylic acid and polyethylene glycol and its derivative
In it is one or more.
7. nano-titanium photo-thermal preparation as claimed in claim 6, which is characterized in that the biocompatible materials are polyethylene glycol
And its derivative, the molecular weight of the polyethylene glycol and its derivative is 200-20000.
8. a kind of preparation method of nano-titanium photo-thermal preparation, which is characterized in that including:
Titanium material is provided, the titanium material is removed using the method that liquid phase is removed, obtains two-dimentional titanium nanometer sheet;
Biocompatible materials are provided, the two-dimentional titanium nanometer sheet and the biocompatible materials are mixed at 10-30 DEG C
After stir 3-6h, obtain nano-titanium photo-thermal preparation.
9. the preparation method of nano-titanium photo-thermal preparation as claimed in claim 8, which is characterized in that the method for the liquid phase stripping
Specifically include following operation:
The titanium material is added in into solvent, Probe Ultrasonic Searching 8-15h is used under ice bath environment;The Probe Ultrasonic Searching terminates
Afterwards, continue using water bath sonicator, the water bath sonicator time is 3-10h, and the temperature of the water-bath is kept for 5-15 DEG C;After ultrasound,
Centrifuged and be dried to obtain two-dimentional titanium nanometer sheet.
10. application of the nano-titanium photo-thermal preparation in photo-thermal therapy drug is prepared as described in any one of claim 1-7.
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