CN110179979A - A kind of composite material and preparation method and application of the copper-based high efficiency anti-tumor of Novel vulcanization - Google Patents
A kind of composite material and preparation method and application of the copper-based high efficiency anti-tumor of Novel vulcanization 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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- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
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Abstract
The invention discloses a kind of novel copper-based high efficiency anti-tumor composite material and preparation method of vulcanization and applications.The described method includes: preparing copper sulphide nano particles in sodium alginate aqueous solution, copper sulphide nano particles and glucose oxidase are carried on mesoporous organosilicon, a kind of novel copper-based high efficiency anti-tumor composite material of vulcanization of rapid synthesis altogether.The composite material has many advantages, such as to prepare convenient, easy to use and antitumous effect significant.Compared with prior art, the composite material combines the photo-thermal effect that copper sulphide nano particles are utilized, photodynamic effect, the addition of glucose oxidase can significantly increase the photodynamic effect of copper sulphide nano particles, can be realized the efficient oncotherapy based on nano-copper sulfide.The composite material has great application value in the efficient therapeutic field of tumor of photoinduction.
Description
Technical field
The invention belongs to field of nanometer technology, and in particular to a kind of novel copper-based high efficiency anti-tumor composite material of vulcanization and
Preparation method and application.
Background technique
Cancer is the main reason for whole world is dead, causes millions of people dead every year.It is controlled currently based on the cancer of phototherapy
Treatment means are due to causing extensive concern with convenience and minimal invasive.Photo-thermal therapy and photodynamic therapy are two kinds main
Phototherapy means both excite photosensitizer by near-infrared laser, efficiently convert light energy into thermal energy or generate high toxicity and live
Property oxygen cluster (usually hydroxyl radical free radical (OH), singlet oxygen (1O2)), both methods can kill tumour cell.Cause
This, light light and heat power synergistic antitumor has objective prospect.
Currently, many inorganic nano materials have been used for light light and heat power synergistic treatment tumour, such as gold nanoshell, Jenner
Rice stick, carbon nanotube and graphite etc..However, this combined strategy often has limitation.Because the photo-thermal therapy of these materials and
Photodynamic therapy usually requires two different excitation wavelengths, causes treatment time very long, and method is complicated.In contrast, recently
It was found that copper sulphide nano particles (CuSNPs) have been demonstrated under near-infrared laser have high photothermal conversion efficiency, can be used for cancer
Disease photo-thermal therapy.Fortunately, copper sulphide nano particles generate reactive oxygen species by photodynamic effect under phase co-wavelength.This
Outside, copper sulphide nano particles size is small, and production cost is low low with cytotoxicity, these advantages become copper sulphide nano particles
Cooperate with the ideal material of photo-thermal and optical dynamic treatment of tumor.However, as far as we know, optical dynamic therapy generates the mistake of reactive oxygen species
Journey is dependent on the hydrogen peroxide (H in tumor microenvironment2O2) content, however in vivo cell content of hydrogen peroxide it is significantly relatively low,
Therefore the effect of the photodynamic therapy treatment tumour of copper sulphide nano particles is not as desired.Therefore, micro- by improving tumour
H in environment2O2Content is very necessary to the optical dynamic therapy of tumour to enhance copper sulphide nano particles.
As a kind of nutriment of key, glucose has played important function in terms of providing energy for tumour growth.
Glucose can be oxidized to gluconic acid and hydrogen peroxide by glucose oxidase (GOD), this is enhancing photodynamic therapy treatment
Tumour provides key tactics.On the other hand, efficient oncotherapy needs selectively to reach nano-carrier into specific disease
Displacement is set and is released medicine in targets neoplastic cells or tumor tissues.In numerous nano-carriers, mesoporous material is excellent
Nanostructure carrier, being capable of load height is dispersed in meso-hole structure catalysis material, it is ensured that excellent reactivity worth and
The free diffusing of reactant or product.It is good to have confirmed that mesoporous silicon dioxide nano particle (MSNs) all has in vitro and in vivo
Good biocompatibility.Therefore, mesoporous silicon dioxide nano particle is considered as one of potential oncotherapy nano-carrier.
To expand application of the nano-copper sulfide sill in oncotherapy, the present invention is using nano-copper sulfide in single wave
Photo-thermal and photodynamic effect synergistic treatment tumour under long near-infrared laser, and by with nano-copper sulfide and grape is glycoxidative
Enzyme mutual load is into mesoporous organosilicon.The glucose of tumor region can be catalyzed into peroxidating abundant by glucose oxidase
Hydrogen, under the excitation of near-infrared laser, hydrogen peroxide can be catalyzed by nano-copper sulfide and generate more reactive oxygen species, and induction is swollen
Apoptosis of tumor and death further enhance the light power effect of nano-copper sulfide.This collection photo-thermal therapy, optical dynamic therapy
The antitumor composite material of one is expected to realize more efficient oncotherapy, is the exploitation of nano-copper sulfide base anti-tumor drug
New method is provided.
Summary of the invention
In order to overcome the shortcomings of the prior art, it is copper-based efficiently anti-swollen that the object of the present invention is to provide a kind of Novel vulcanizations
The composite material and preparation method and application of tumor.
Preparation method provided by the invention at room temperature, vulcanizes by template and the preparation of stabilizer green of sodium alginate
Copper nano-particle, and it is carried on mesoporous organosilicon with glucose oxidase altogether, collection photo-thermal therapy is prepared, light power is controlled
It treats in the high efficiency anti-tumor composite material of one.Composite material obtained simultaneously utilize copper sulphide nano particles photo-thermal effect,
Photodynamic effect realizes more efficient oncotherapy.
The purpose of the present invention is realized at least through one of following technical solution.
A kind of preparation method of the composite material of the copper-based high efficiency anti-tumor of Novel vulcanization provided by the invention, including walk as follows
It is rapid:
(1) ammonium hydroxide is added drop-wise in copper-bath, obtains cupric ammine complex solution (i.e. [Cu (NH3)4]2+Solution)；
(2) step (1) the cupric ammine complex solution is added in sodium alginate soln, stir process (room temperature) obtains
To composite solution；
(3) sodium sulfide solution is added drop-wise in the composite solution that step (2) obtains under stirring at normal temperature state, is then stirred
It handles (room temperature), obtains copper sulphide nano particles solution；
(4) mesoporous organosilicon is added to the water, is uniformly mixing to obtain mesoporous organosilicon suspension；Then by grape glycosyloxy
Change enzyme solutions and mesoporous organosilicon suspension be added in step (3) described copper sulphide nano particles solution, stir process (room temperature),
Centrifuging and taking precipitating, obtains the composite material of the copper-based high efficiency anti-tumor of the Novel vulcanization.
Further, the mass percent concentration of step (1) described ammonium hydroxide is 1-10wt%；The copper-bath it is dense
Degree is 0.2-3mg/mL；The molar ratio of the solute ammonia of the solute copper sulphate and ammonium hydroxide of copper-bath described in step (1) is
1:(1-10)。
Further, the volume ratio between step (2) the cupric ammine complex solution and sodium alginate soln is 1:1-2；
The concentration of step (2) described sodium alginate soln is 1-10mg/mL.
Further, the stirring rate of step (2) described stir process is 200-600rpm, mixing time 0.5h-5h.
Further, step (3) stirring rate under stirring is 200-600rpm；The sodium sulfide solution
Concentration be 1-10mg/mL；The volume ratio of the sodium sulfide solution and composite solution is 1:2-6；The copper sulphide nano particles
The concentration of solution is 0.2-3mg/mL；The stirring rate of the stir process is 200-600rpm, and the time of stir process is
0.5-2h。
Further, the mass volume ratio of step (4) mesoporous organosilicon and water is 1-10:1mg/L；The glucose
The concentration for aoxidizing enzyme solutions is 1-10mg/mL；Step (4) the copper sulphide nano particles solution and glucose oxidase solution
Volume ratio is 15-30:1；The volume ratio of the copper sulphide nano particles solution and mesoporous organosilicon suspension is 15-30:1.
Further, the rate of step (4) described stir process is 200-600rpm, and the time of stir process is 8-15h；
The rate of the centrifugation is 3000-8000rpm, and the time of centrifugation is 5-15min.
The present invention provides a kind of composite material that the copper-based high efficiency anti-tumor of Novel vulcanization is made by above-mentioned preparation method.
The composite material of the copper-based high efficiency anti-tumor of Novel vulcanization provided by the invention can be applied to killing tumour cell.
Further, the application of the composite material of the copper-based high efficiency anti-tumor of the Novel vulcanization, includes the following steps:
By tumor cell inoculation tissue culture plate, by the composite material dissolution of the copper-based high efficiency anti-tumor of the Novel vulcanization in
It in DMSO solution, is added on tissue culture plate, is incubated for jointly with tumour cell, wash, culture medium is replaced, using near-infrared laser
Irradiation monitors cell killing situation using real-time dynamic living cells imaging system.
Further, the solute copper sulphate of copper-bath described in step (1) and sodium alginate described in step (2) are molten
Mass ratio between the solute sodium alginate of liquid is 1:1-10.
Further, the solute copper sulphate of copper-bath described in step (1) and sodium sulfide solution described in step (3)
Solute vulcanized sodium between mass ratio be 1:1-10.
Further, the solute copper sulphide nano particles of copper sulphide nano particles solution described in step (4) and step (4)
Described in mass ratio between mesoporous organosilicon be 1:1-10.
Further, the solute glucose oxidase and mesoporous organosilicon of glucose oxidase solution described in step (4)
Mass ratio be 1:1-10.
A kind of composite material that the copper-based high efficiency anti-tumor of Novel vulcanization being made by above-mentioned preparation method provided by the invention.
Compared with prior art, the invention has the advantages that and the utility model has the advantages that
(1) preparation method provided by the invention utilizes nano-copper sulfide photo-thermal effect, photodynamic effect, and passes through glucose
The addition of oxidizing ferment enhances photodynamic effect, and the composite material of the copper-based high efficiency anti-tumor of Novel vulcanization is made, which has very well
Antitumous effect.
(2) preparation method provided by the invention, step is simple, low in cost, green high-efficient.
Detailed description of the invention
Fig. 1 a is the TEM figure of copper sulphide nano particles made from embodiment 2；
Fig. 1 b is the grain size distribution of copper sulphide nano particles made from embodiment 2；
Fig. 2 a is the uv absorption spectra of copper sulphide nano particles solution made from embodiment 2；
Fig. 2 b is the XRD spectra of copper sulphide nano particles made from embodiment 2；
Fig. 3 a and Fig. 3 b are the TEM figure of the mesoporous organosilicon of embodiment 2；
Fig. 3 c and Fig. 3 d are glucose oxidase made from embodiment 2 and copper sulphide nano particles mutual load in mesoporous
The TEM of organosilicon schemes (different amplification)；
Fig. 4 a is photothermal response curve of the composite material of the preparation of embodiment 2 under various concentration；
Fig. 4 b is photothermal response curve of the composite material of the preparation of embodiment 2 under different laser powers；
Fig. 5 a is that composite material prepared by embodiment 2 is making agent for capturing using 2,2,6,6- tetramethyl piperidine-nitrogen-oxide
Whether there is or not glucose or whether there is or not the paramagnetic resonance spectrums under near-infrared laser；
Fig. 5 b is catalyzed 3,3 ', 5,5 '-tetramethyl benzidines for composite material prepared by embodiment 2 under near-infrared laser and shows
Color UV-quantitative analysis figure；Fig. 5 c is the curve being fitted according to Fig. 5 b；
Fig. 5 d, which is composite material, to be coughed up quinoline-N- oxide and makees agent for capturing whether there is or not glucose being given a tongue-lashing using 5,5- dimethyl -1-
Or whether there is or not the paramagnetic resonance spectrums under near-infrared laser；
Fig. 5 e is that composite material prepared by embodiment 2 is catalyzed 1,3 diphenyl isobenzofuran colour fading under near-infrared laser
UV-quantitative analysis figure；Fig. 5 f is the curve being fitted according to Fig. 5 e；
Fig. 5 g be embodiment 2 prepare composite material under different concentration of glucose glucose oxidase catalysis generate peroxide
Change the enzyme kinetics curve of hydrogen；Fig. 5 h is the Michaelis-Menten kinetics fit equation being fitted by 5g；Figure
5i is the Linerweaver-Bruker fit equation being fitted by 5g；
Fig. 6 a is cell imaging figure of 2 tumour cell of embodiment before composite material is added；
Fig. 6 b is cell imaging figure of 2 tumour cell of embodiment after composite material is added for 24 hours；
Composite material is added for 24 hours afterwards through 808nm, 1.5W/cm in administration in Fig. 6 c tumour cell2Near-infrared laser irradiation
The cell imaging figure of 5min.
Specific embodiment
Specific implementation of the invention is described further below in conjunction with attached drawing and example, but implementation and protection of the invention
It is without being limited thereto.If it is existing to be that those skilled in the art can refer to it is noted that there is the not special process of detailed description below
Technology realize or understand.
Embodiment 1
A kind of preparation method of the composite material for the copper-based high efficiency anti-tumor of Novel vulcanization that embodiment 1 provides, including it is as follows
Step:
(1) compound concentration is the copper-bath of 0.4mg/mL, and ammonium hydroxide is added drop-wise to by the ammonium hydroxide that mass fraction is 1%
In the copper-bath of 30mL, the molar ratio of the solute ammonia of the solute copper sulphate and ammonium hydroxide of the copper-bath is 1:1, is stirred
Mix uniformly obtained cupric ammine complex solution；
(2) compound concentration be 1mg/mL sodium alginate soln, then mixed with cupric ammine complex solution, under room temperature with
The revolving speed of 200rpm is stirred 0.5h, and the volume ratio of cupric ammine complex solution and sodium alginate soln is 1:1, obtains compound molten
Liquid；
(3) mass concentration is added dropwise to for the sodium sulfide solution of 2mg/mL in the case where room temperature is with the rate stirring of 200rpm
In above-mentioned composite solution, the volume ratio of the sodium sulfide solution and composite solution is 1:2, and rear stir process is added dropwise and obtains
Copper sulphide nano particles solution, the time of stir process are 0.5h, and the rate of stir process is 200rpm；
(4) by concentration be 0.2mg/mL copper sulphide nano particles solution, concentration be 1mg/mL glucose oxidase it is molten
Liquid is stirred at room temperature with the mesoporous organosilicon suspension that concentration is 2mg/mL, stirring rate 200rpm, and mixing time is
15h, three's volume ratio are 15:1:1, take in precipitating that obtain the Novel vulcanization copper-based efficiently anti-after 3000rpm is centrifuged 5min
The composite material of tumour.
Embodiment 2
A kind of preparation method of the composite material for the copper-based high efficiency anti-tumor of Novel vulcanization that embodiment 2 provides, including it is as follows
Step:
(1) compound concentration is the copper-bath of 1mg/mL, and mass fraction is 2.5% ammonium hydroxide, and ammonium hydroxide is added drop-wise to 30mL
Copper-bath in, the molar ratio of the solute ammonia of the solute copper sulphate and ammonium hydroxide of the copper-bath is 1:2, and stirring is equal
Even obtained cupric ammine complex solution；
(2) compound concentration be 4mg/mL sodium alginate soln, then mixed with cupric ammine complex solution, under room temperature with
The revolving speed of 400rpm is stirred 3h, and the volume ratio of cupric ammine complex solution and sodium alginate soln is 1:1, obtains compound molten
Liquid；
(3) mass concentration is added dropwise to for the sodium sulfide solution of 5mg/mL in the case where room temperature is with the rate stirring condition of 400rpm
In above-mentioned composite solution, the volume ratio of the sodium sulfide solution and composite solution is 1:4, and rear stir process is added dropwise and obtains
Copper sulphide nano particles, the time of stir process are 1h, and the rate of stir process is 400rpm；
(4) by concentration be 0.8mg/mL copper sulphide nano particles solution, concentration be 3mg/mL glucose oxidase it is molten
Liquid is stirred at room temperature with the mesoporous organosilicon suspension that concentration is 4mg/mL, stirring rate 400rpm, and mixing time is
9h, three's volume ratio are 20:1:1, and it is copper-based efficiently anti-to obtain the Novel vulcanization in precipitating after 5000rpm is centrifuged 10min
The composite material of tumour.
Embodiment 3
A kind of preparation method of the composite material for the copper-based high efficiency anti-tumor of Novel vulcanization that embodiment 3 provides, including it is as follows
Step:
(1) compound concentration is the copper-bath of 2mg/mL, and ammonium hydroxide is added drop-wise to 30mL by the ammonium hydroxide that mass fraction is 5%
Copper-bath in, the molar ratio of the solute ammonia of the solute copper sulphate and ammonium hydroxide of the copper-bath is 1:5, and stirring is equal
Even obtained cupric ammine complex solution；
(2) compound concentration be 5mg/mL sodium alginate soln, then mixed with cupric ammine complex solution, under room temperature with
The revolving speed of 400rpm is stirred 3h, and the volume ratio of cupric ammine complex solution and sodium alginate soln is 1:1.5, obtains compound molten
Liquid；
(3) mass concentration is added dropwise to for the sodium sulfide solution of 7mg/mL in the case where room temperature is with the rate stirring condition of 400rpm
In above-mentioned composite solution, the volume ratio of the sodium sulfide solution and composite solution is 1:4, and rear stir process is added dropwise and obtains
Copper sulphide nano particles solution, the time of stir process are 1h, and the rate of stir process is 400rpm；
(4) by concentration be 1.5mg/mL copper sulphide nano particles solution, concentration be 5mg/mL glucose oxidase it is molten
Liquid is stirred at room temperature with the mesoporous organosilicon suspension that concentration is 7mg/mL, stirring rate 400rpm, and mixing time is
10h, three's volume ratio are as follows: it is copper-based efficiently to obtain the Novel vulcanization after 4000rpm is centrifuged 10min in precipitating by 20:1:1
Antitumor composite material.
Embodiment 4
A kind of preparation method of the composite material for the copper-based high efficiency anti-tumor of Novel vulcanization that embodiment 4 provides, including it is as follows
Step:
(1) compound concentration is the copper-bath of 2.5mg/mL, and mass fraction is 10% ammonium hydroxide, and ammonium hydroxide is added drop-wise to 30mL
Copper-bath in, the molar ratio of the solute ammonia of the solute copper sulphate and ammonium hydroxide of the copper-bath is 1:10, stirring
Uniformly obtained cupric ammine complex solution；
(2) compound concentration be 10mg/mL sodium alginate soln, then mixed with cupric ammine complex solution, under room temperature with
The revolving speed of 600rpm is stirred 5h, and the volume ratio of cupric ammine complex solution and sodium alginate soln is 1:2, obtains compound molten
Liquid；
(3) mass concentration is added dropwise to for the sodium sulfide solution of 9mg/mL in the case where room temperature is with the rate stirring condition of 600rpm
In above-mentioned composite solution, the volume ratio of the sodium sulfide solution and composite solution is 1:6；Rear stir process is added dropwise to obtain
Copper sulphide nano particles solution, the time of stir process are 2h, and the rate of stir process is 600rpm；
(4) by concentration be 2.5mg/mL copper sulphide nano particles solution, concentration be 9mg/mL glucose oxidase it is molten
Liquid is stirred at room temperature with the mesoporous organosilicon suspension that concentration is 8mg/mL, stirring rate 600rpm, and mixing time is
8h, three's volume ratio are 30:1:1, and it is copper-based efficiently anti-swollen to obtain the Novel vulcanization in precipitating after 8000rpm is centrifuged 5min
The composite material of tumor.
Interpretation of result:
Fig. 1 a is the TEM figure of copper sulphide nano particles made from embodiment 2.From Fig. 1 a it is found that method provided by the invention
Copper sulphide nano particles obtained are uniformly dispersed, dimensionally stable, partial size about 10nm, it can clearly be seen that nanometer from high power photo
The lattice fringe of particle；Fig. 1 b is the particle diameter distribution of copper sulphide nano particles made from embodiment 2, gained nano particle diameter point
Cloth is narrow, average grain diameter 12.9nm.Other embodiments effect is similar to Example 2, can refer to Fig. 1 a and Fig. 1 b.
Fig. 2 a is the uv absorption spectra of copper sulphide nano particles solution made from embodiment 2, from Fig. 2 a it is found that this hair
The copper sulphide nano particles of the method preparation of bright offer have strong near infrared absorption, the absorption peak with copper sulphide nano particles
Position is essentially identical (ACS nano, 2015,9 (7): 7085-7096)；Fig. 2 b is copper sulphide nano particles made from embodiment 2
XRD spectra, there is apparent characteristic diffraction peak, respectively correspond (101), (102), (103), (006), (105), (110),
(108), (202), (116) crystal face, this is consistent with standard card JCPDS (no.06-0464), meets the crystal form of copper sulfide.Its
His embodiment effect is similar to Example 2, can refer to Fig. 2 a and Fig. 2 b.
Fig. 3 a, Fig. 3 b are that 2 copper sulphide nano particles of embodiment and glucose oxidase are carried on mesoporous organosilicon altogether and are made
Compound TEM figure, Fig. 3 c and Fig. 3 d are that glucose oxidase made from embodiment 2 and copper sulphide nano particles are born jointly
It is loaded in the TEM figure of mesoporous organosilicon；From Fig. 3 a, Fig. 3 b, Fig. 3 c and Fig. 3 d it is found that partial size about 100nm mesoporous organosilicon nanometer
Particle surface is uneven, and has meso-hole structure；Copper sulphide nano particles and glucose oxidase are filled in organosilicon
After meso-hole structure, surface becomes relative smooth, full.
The external photothermal response performance of composite material prepared by embodiment 2 is known that from Fig. 4 a, Fig. 4 b.Fig. 4 a composite wood
Expect the photothermal response curve under corresponding different copper sulphide nano particles concentration, as seen from the figure, the concentration of composite material is got over
Bloom thermo-responsive is stronger.Fig. 4 b is the photothermal response curve under composite material difference laser power, as seen from the figure, laser
The power the high more bloom thermo-responsive is stronger.Fig. 4 a and Fig. 4 b illustrate that prepared vulcanization Cu-base composites are imitated with photo-thermal
It answers, the energy of near-infrared laser can be converted to thermal energy, can be applied to photo-thermal therapy for tumor.
Fig. 5 a is that composite material prepared by embodiment 2 is made agent for capturing and existed using 2,2,6,6- tetramethyl piperidine-nitrogen-oxide
Whether there is or not glucose or whether there is or not the paramagnetic resonance spectrums under near-infrared laser, excite it can be seen from Fig. 5 a without near-infrared laser, multiple
Condensation material does not generate peak, and the peak of 1:2:2:1 is generated under near-infrared laser excitation, illustrates there is hydroxyl radical free radical (OH) production
It is raw, and the intensity of glucose postpeak has been added to significantly increase, illustrate that the addition of glucose facilitates hydroxyl radical free radical generation.Figure
5b, Fig. 5 c are respectively that 3,3 ', 5,5 '-tetramethyl benzidines are catalyzed under near-infrared laser is aobvious for the composite material for preparing of embodiment 2
The curve of color UV-quantitative analysis figure and fitting, by Fig. 5 b, Fig. 5 c as it can be seen that composite material generates under near-infrared laser irradiation
Generation hydroxyl radical free radical (OH) can be incremented by with the time, and compound first order reaction kinetics model.Fig. 5 d is embodiment 2
The composite material of preparation makees agent for capturing whether there is or not glucose or whether there is or not under near-infrared laser using 1,3 diphenyl isobenzofurans
Paramagnetic resonance spectrum excites it can be seen from Fig. 5 d without near-infrared laser, and composite material does not generate peak, and swashs in near-infrared
The lower peak for generating 1:1:1 of light excitation, illustrate to have singlet oxygen (1O2) generate, and the intensity of glucose postpeak has been added significantly to increase
By force, illustrate that the addition of glucose facilitates singlet oxygen generation.Fig. 5 e, Fig. 5 f are respectively that the composite material of the preparation of embodiment 2 exists
The UV-quantitative analysis figure of 1,3 diphenyl isobenzofurans colour fading and the curve of fitting are catalyzed under near-infrared laser, by Fig. 5 b, figure
The visible singlet oxygen that under near-infrared laser irradiation, composite material is generated of 5c (1O2) can be incremented by with the time, and meet two
Order reaction kinetic model.Fig. 5 g is the enzymatic reaction that composite material oxidizing glucose prepared by embodiment 2 generates hydrogen peroxide
Kinetic curve, the amount that hydrogen peroxide generates are calculated for 5% titanium sulfate solution according to standard curve by mass fraction.By scheming
Composite material prepared by embodiment 2 known to 5g can be produced due to joined glucose oxidase as the addition of glucose is catalyzed
Raw hydrogen peroxide, and with the increase of glucose amount, the amount of hydrogen peroxide also increases.Fig. 5 h, Fig. 5 i are respectively quasi- according to Fig. 5 g
The Michaels-Menten curve and Linerweaver-Bruker curve of conjunction, can illustrate that the enzymatic of composite material reacts
Meet the model of michaelis-Menton kinetics.It can be seen that from these figures, vulcanization Cu-base composites prepared by embodiment 2 are dynamic with light
Power effect, and light power effect can be further enhanced under conditions of glucose oxidase glucose is hydrogen peroxide, it can be with
Applied to photodynamic therapy treatment tumour.Other embodiments effect is similar to Example 2, can refer to Fig. 5 a, Fig. 5 b, Fig. 5 c, figure
5d, Fig. 5 e, Fig. 5 f, Fig. 5 g, Fig. 5 h and Fig. 5 i.
Target cell of the human breast cancer cell (MCF-7) as experiment in vitro is selected, system is imaged using real-time dynamic living cells
(IncuCyte ZOOM Real-Time Live-Cell Imaging System, Essen Bioscience) is united to external swollen
Oncocyte killing effect is investigated.MCF-7 breast cancer tumor cells are inoculated into 96 porocyte culture plates of black, when experiment
First cell is washed 3 times using physiological saline.By the composite material sol of the copper-based high efficiency anti-tumor of Novel vulcanization made from embodiment 2
Solution (concentration is 6.25 μ g/mL) in DMSO, is incubated for for 24 hours jointly with cell；Before near-infrared laser irradiation, MCF-7 cell is through PBS
Cleaning 2 times, and complete medium (containing serum) is changed, then use 1.5W/cm2Near-infrared laser, irradiating cell 5min.This
Afterwards, cell proliferation situation and cytotoxicity and cell killing are monitored.Fig. 6 a, Fig. 6 b and Fig. 6 c are that embodiment 2 is made
The composite material obtained is used for the cell imaging figure of Vitro Tumor treatment.Fig. 6 a be tumour cell before administration without occur it is dead/
Non-viable non-apoptotic cell image；Fig. 6 b is tumour cell after administration for 24 hours, and composite material has into inside tumor cells, also has glutinous
It is attached to tumor cell surface, tumour cell is still without there is the cell imaging figure of dead/necrosis；Fig. 6 c is that tumour cell exists
Administration is for 24 hours afterwards through 808nm, 1.5W/cm2Near-infrared laser irradiation 5min cell imaging figure, available from Fig. 6 c, tumour is thin
Born of the same parents issue fluorescence, and cell mortality nearly reaches 100%.Other embodiments effect is similar to Example 2, can refer to Fig. 6 a, figure
6b and Fig. 6 c.
From the analysis above, we can see that preparation method provided by the invention makees the templated synthesis copper sulfide nano grain of rice using sodium alginate
Son, and by it with glucose oxidase mutual load in mesoporous organosilicon, it is copper-based efficiently anti-to prepare a kind of novel vulcanization
Tumour composite material.This composite material has good photothermal conversion effect and light power effect, and can be in glucose oxidase
In the presence of further enhance light power effect, its antitumous effect of In vitro cell experiment surface is excellent, in terms of oncotherapy
There is huge application potential.
Above embodiments are only preferrred embodiment of the present invention, for explaining only the invention, are not intended to limit the present invention, this
Field technical staff should belong to guarantor of the invention without departing from change made under spirit of the invention, replacement, modification etc.
Protect range.
Claims (10)
1. a kind of preparation method of the composite material of the copper-based high efficiency anti-tumor of Novel vulcanization, which comprises the steps of:
(1) ammonium hydroxide is added drop-wise in copper-bath, obtains cupric ammine complex solution；
(2) step (1) the cupric ammine complex solution is added in sodium alginate soln, stir process obtains composite solution；
(3) sodium sulfide solution is added drop-wise in the composite solution that step (2) obtains under stirring, then stir process, obtains
To copper sulphide nano particles solution；
(4) mesoporous organosilicon is added to the water, is uniformly mixing to obtain mesoporous organosilicon suspension；Then by glucose oxidase
Solution and mesoporous organosilicon suspension are added in step (3) described copper sulphide nano particles solution, stir process, and centrifuging and taking is heavy
It forms sediment, obtains the composite material of the copper-based high efficiency anti-tumor of the Novel vulcanization.
2. preparation method according to claim 1, which is characterized in that the mass percent concentration of step (1) described ammonium hydroxide
For 1-10wt%；The concentration of the copper-bath is 0.2-3mg/mL；The solute sulfuric acid of copper-bath described in step (1)
The molar ratio of the solute ammonia of copper and ammonium hydroxide is 1:(1-10).
3. preparation method according to claim 1, which is characterized in that step (2) the cupric ammine complex solution and seaweed
Volume ratio between acid sodium solution is 1:1-2；The concentration of step (2) described sodium alginate soln is 1-10mg/mL.
4. preparation method according to claim 1, which is characterized in that the stirring rate of step (2) described stir process is
200-600rpm, mixing time 0.5h-5h.
5. preparation method according to claim 1, which is characterized in that step (3) the stirring speed under stirring
Rate is 200-600rpm；The concentration of the sodium sulfide solution is 1-10mg/mL；The volume of the sodium sulfide solution and composite solution
Than for 1:2-6；The concentration of the copper sulphide nano particles solution is 0.2-3mg/mL；The stirring rate of the stir process is
200-600rpm, the time of stir process are 0.5-2h.
6. preparation method according to claim 1, which is characterized in that the quality of step (4) mesoporous organosilicon and water
Volume ratio is 1-10:1mg/L；The concentration of the glucose oxidase solution is 1-10mg/mL；Step (4) described copper sulfide nano
The volume ratio of rice corpuscles solution and glucose oxidase solution is 15-30:1；The copper sulphide nano particles solution has with mesoporous
The volume ratio of machine silicon suspension is 15-30:1.
7. preparation method according to claim 1, which is characterized in that the rate of step (4) described stir process is 200-
600rpm, the time of stir process are 8-15h；The rate of the centrifugation is 3000-8000rpm, and the time of centrifugation is 5-
15min。
8. a kind of composite wood that the copper-based high efficiency anti-tumor of Novel vulcanization is made by the described in any item preparation methods of claim 1-7
Material.
9. the composite material of the copper-based high efficiency anti-tumor of Novel vulcanization according to any one of claims 8 is killing the application in tumour cell.
10. application according to claim 9, which comprises the steps of:
By tumor cell inoculation tissue culture plate, the composite material of the copper-based high efficiency anti-tumor of the Novel vulcanization is dissolved in DMSO
It in solution, is added on tissue culture plate, is incubated for jointly with tumour cell, wash, replace culture medium, irradiated using near-infrared laser
Tumour cell is killed, situation is killed using real-time dynamic living cells imaging system monitoring tumour cell.
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| CN113633660A (en) * | 2021-08-13 | 2021-11-12 | 哈尔滨工程大学 | Preparation method of bimetallic nano-enzyme composite material with in-situ tumor microenvironment regulation and anti-tumor effect |
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| CN111388451A (en) * | 2020-04-29 | 2020-07-10 | 南京工业大学 | Protein self-assembly iron-based nanoparticle, preparation method thereof and application of nanoparticle in antitumor drug delivery system |
| CN111956617A (en) * | 2020-08-21 | 2020-11-20 | 中国科学院金属研究所 | Targeting microsphere with long-acting anti-tumor characteristic and preparation method thereof |
| CN111956617B (en) * | 2020-08-21 | 2023-01-13 | 中国科学院金属研究所 | Targeting microsphere with long-acting anti-tumor characteristic and preparation method thereof |
| CN113633660A (en) * | 2021-08-13 | 2021-11-12 | 哈尔滨工程大学 | Preparation method of bimetallic nano-enzyme composite material with in-situ tumor microenvironment regulation and anti-tumor effect |
| CN114652819A (en) * | 2022-03-21 | 2022-06-24 | 滨州医学院 | Degradable multifunctional nano material for targeting tumor microenvironment and preparation method thereof |
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