CN107184979A - Copper-zinc-tin-sulfur quaternary nano composite material and its preparation and application method with microwave enhanced sensitivity and NMR imaging function - Google Patents
Copper-zinc-tin-sulfur quaternary nano composite material and its preparation and application method with microwave enhanced sensitivity and NMR imaging function Download PDFInfo
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Abstract
The invention discloses a kind of copper-zinc-tin-sulfur quaternary nano composite material and its preparation and application method with microwave enhanced sensitivity and NMR imaging function, biocompatiblity molecules of the copper-zinc-tin-sulfur quaternary nano composite material with microwave enhanced sensitivity and NMR imaging function comprising nanometer copper zincium tin sulfur compound with the compound surface.There is the copper-zinc-tin-sulfur quaternary nano composite material of microwave enhanced sensitivity and NMR imaging function can be combined together microwave heat therapeutic and microwave induced photodynamic therapy for this, with excellent oncotherapy effect.
Description
Technical field
It is more particularly to biomedical to use the nano combined material of copper-zinc-tin-sulfur quaternary the present invention relates to the field of biomedical material
The field of material.
Background technology
The high incidence of cancer and the death rate persistently risen seriously threaten global public health safety.Traditional cancer
Treatment method is such as performed the operation, chemotherapy and radiation will inevitably produce larger toxic side effect to human body, such as injures normal
Cell, tissue, destruction immune system etc..
It is used as a kind of new treatment means, light therapy（Photodynamic therapy）Pass through the sensitiser absorption light in patient's body
Can, it is excited produces excessive active oxygen or generation high temperature thereafter, its dead mode is carried out with cancer cell reaction.Because of it
The selectivity and specificity of instinct, it is possible to prevente effectively from the generation of problem described in above-mentioned traditional therapy, is controlled as cancer
The preferred approach for the treatment of.But in the prior art, phototherapy penetration depth is limited, its application in clinic significantly limit.
The frequency of microwave is 300 ~ 3000 MHz, and its wavelength ratio near-infrared wavelength is longer, and effectively depth is penetrated with stronger
Degree.In recent years, the reinforcing microwave heat therapeutic research based on confinement effect obtains certain progress, is such as loaded using sodium alginate micro gel capsule
Physiological saline as tumor microwave heat treatment in a kind of reinforcement sensitizer；Use hollow nanoparticle zirconium dioxide and dopamine
Possess highly polar and significant Microwave Absorption Properties after supported ion liquid, microwave heat therapeutic sensitizer etc. can be used as.These are new
The further application of nano composite material is still limited by following reason：Charging ratio of the hollow nanoparticle to ionic liquid
Low, composite intermediate ion liquid accidental release can cause genotoxic potential and reduce therapeutic efficiency, nanoparticle as ionic liquid
The carrier of body and in oncotherapy in be not revealed in physicochemical property.
The content of the invention
It is an object of the invention to propose a kind of to be combined together microwave heat therapeutic and microwave induced photodynamic therapy
, new material with microwave enhanced sensitivity and NMR imaging function, the further object of the present invention is the system for disclosing the new material
Standby and application process.
Technical scheme is as follows：
A kind of copper-zinc-tin-sulfur quaternary nano composite material with microwave enhanced sensitivity and NMR imaging function, it includes Nanometer Copper zinc-tin
The biocompatiblity molecules of sulphur compound and the compound surface.
Preferably：The particle diameter of the nanometer copper zincium tin sulfur compound is 2 ~ 20 nm.
It is also preferred that：The biocompatiblity molecules are selected from polyethylene glycol, bovine serum albumin(BSA), chitosan, bright
One or more in glue.
It is further preferably：The molecular weight polyethylene glycol is 0.3 ~ 100,000；It is preferred that, the peg molecule
Measure as 0.5 ten thousand.
The present invention further discloses the above-mentioned copper-zinc-tin-sulfur quaternary nanometer with microwave enhanced sensitivity and NMR imaging function is multiple
The preparation method of condensation material, it comprises the following steps：
Presoma respectively containing copper, zinc, the presoma of the copper of tin element, the presoma of zinc, tin is dissolved in the first solvent jointly
In, obtain precursor solution A；
The presoma of sulphur containing element sulphur is dissolved in the second solvent, precursor solution B is obtained；
The precursor solution A is heated to after 150 ~ 230 DEG C, the precursor solution B is rapidly injected, both are mutually reciprocal thereafter
Answer 0.5 ~ 5h；After the mixed solution that both constitute is cooled to room temperature, adds after the 3rd solvent and centrifuge, obtain solid matter
Based on nanometer copper zincium tin sulfur compound；
The basic nanometer copper zincium tin sulfur compound is mixed with biocompatiblity molecules, 10 ~ 120min of ultrasound, shakes thereafter thereafter
6 ~ 24h, concussion is centrifuged after terminating, and gained solid matter is the described copper with microwave enhanced sensitivity and NMR imaging function
Zinc-tin sulphur quaternary nano composite material.
First solvent is preferably ethylene glycol.
Second solvent preferably is selected from the one or more in methanol, ethanol, isopropanol, ethylene glycol.
3rd solvent is preferably ethanol.
The mass ratio of the biocompatiblity molecules and the basic nanometer copper zincium tin sulfur compound is preferably 0.2:1~2:
1。
The biocompatiblity molecules preferably are selected from one kind or many in polyethylene glycol, bovine serum albumin(BSA), chitosan, gelatin
Kind.
It is more preferably that the molecular weight polyethylene glycol is 0.3 ~ 100,000；More preferably described peg molecule
Measure as 0.5 ten thousand.
The presoma of the copper preferably is selected from the one or more in copper chloride, stannous chloride, acetic acid copper liquor；The zinc
Presoma preferably be selected from one or more in zinc chloride, zinc acetate aqueous solution；The presoma of the tin preferably is selected from stannic chloride, nitre
One or more in the sour tin aqueous solution；The presoma of the sulphur preferably is selected from the one or more in vulcanized sodium, thiourea solution.
The concentration of the presoma of the copper is preferably 40 ~ 60mM, more preferably 50mM, and the concentration of the presoma of zinc is preferably
20 ~ 40mM, more preferably 30mM, the concentration of the presoma of tin is preferably 20 ~ 40mM, more preferably 30mM.
The present invention further discloses the described copper-zinc-tin-sulfur quaternary nanometer with microwave enhanced sensitivity and NMR imaging function
The copper-zinc-tin-sulfur quaternary with microwave enhanced sensitivity and NMR imaging function that composite or described preparation method are prepared is received
The application process of nano composite material, for the copper-zinc-tin-sulfur quaternary with microwave enhanced sensitivity and NMR imaging function is nano combined
Materials application is in treatment of cancer and/or NMR imaging.
It is specifically：When it is applied in treatment of cancer, as the sensitizer in the microwave heat therapeutic of cancer and/or
Sensitising agent in the optical dynamic therapy of cancer, and/or be further used as in treatment of cancer carry out NMR imaging when radiography
Agent.
The copper-zinc-tin-sulfur quaternary nano composite material with microwave enhanced sensitivity and NMR imaging function also can be separately as
In contrast agent application and NMR imaging during NMR imaging.
The copper-zinc-tin-sulfur quaternary nano composite material of the present invention is in clinic because it is in the microwave absorption of microwave equipment frequency range
Characteristic, can be as the sensitizer in microwave heat therapeutic, so as to produce microwave heat therapeutic effect；It is under near-infrared or microwave irradiation simultaneously
Singlet oxygen can be produced at tumour, with microwave induced optical dynamic therapy effect；The combination of both effects, makes it have
To the efficient accurately therapeutic effect of tumour.
In addition, the nanometer copper zincium tin sulfur compound in the composite has special magnetic property, in the present invention by
Its obtained composite, is detected still have Magnetic resonance imaging function, therefore further can be played in treatment of cancer
The effect of radiography, this also makes it have more significant advantage in the Nano medication as treatment of cancer.
The present invention possesses following beneficial effect：
（1）The present invention's has the copper-zinc-tin-sulfur quaternary nano composite material of microwave enhanced sensitivity and NMR imaging function in oncotherapy
When, microwave heat therapeutic can be combined with microwave induced optical dynamic therapy simultaneously；
（2）The present invention's has the copper-zinc-tin-sulfur quaternary nano composite material of microwave enhanced sensitivity and NMR imaging function in oncotherapy
When, while with therapeutic effect, NMR imaging can be carried out；
（3）The copper-zinc-tin-sulfur quaternary nano composite material with microwave enhanced sensitivity and NMR imaging function of the present invention has in treatment
Have the advantages that penetration power is strong, directive property is good, focusing is good, traumatic small, low toxicity, applied widely, treatment degree it is thorough, simultaneously
Chemicotherapy can be cooperateed with to improve treatment of cancer effect；
（4）The present invention's has the copper-zinc-tin-sulfur quaternary nano composite material of microwave enhanced sensitivity and NMR imaging function in the treatment
When, the observation of dynamic NMR imaging can be combined, tight monitoring is carried out to conditions of patients, lasting point is carried out to therapeutic effect
Analysis；
（5）The present invention have microwave enhanced sensitivity and NMR imaging function copper-zinc-tin-sulfur quaternary nano composite material need not load from
Sub- liquid or physiological saline isopolarity molecule, material has extraordinary microwave temperature-raising characteristic in itself；Pass through transmission in microwave
Effect enters after tumor tissues, and it makes lesions position quick heating, and tissue internal-external temperature difference substantially, thus causes obvious physiology anti-
Should, the ion concentration in such as tumour cell is changed, protein synthesis is suppressed, cell loss multiplication capacity；
（6）The present invention's has the copper-zinc-tin-sulfur quaternary nano composite material of microwave enhanced sensitivity and NMR imaging function in microwave irradiation
Under can produce singlet oxygen in affected area, singlet oxygen can directly kill tumour cell, while destroying the hair of near tumor cells
Thin blood vessel, blocks tumor vessel, cuts off the nutrition supply of tissue, thus reach it is right in the case where not injuring normal structure
The purpose that tumour is killed；
（7）The present invention's has the copper-zinc-tin-sulfur quaternary nano composite material of microwave enhanced sensitivity and NMR imaging function because it is unique
Quaternary component and structure, with the good enhanced functions of NMR imaging T1；
（8）The preparation method process of the present invention is simple, and easy to operate, it is not necessary to special installation, simultaneous reactions raw material is easy to get, reaction
Temperature is gentle, and production cost is relatively low；
（9）The all environmentally friendly solvents used in the preparation method of the present invention, health environment-friendly.
Brief description of the drawings
Fig. 1 shines for the transmission electron microscope of the copper-zinc-tin-sulfur quaternary nano composite material obtained by the embodiment of the present invention 1
Piece；
Fig. 2 schemes for the microwave heating of the copper-zinc-tin-sulfur quaternary nano composite material obtained by the embodiment of the present invention 1；
Fig. 3 is the NMR imaging T1 enhancing figures of the copper-zinc-tin-sulfur quaternary nano composite material of the gained of the embodiment of the present invention 1.
Embodiment
Copper-zinc-tin-sulfur quaternary nano composite material of the present invention with microwave enhanced sensitivity and NMR imaging function is included
Biocompatiblity molecules of the copper-zinc-tin-sulfur quaternary nano composite material comprising nanometer copper zincium tin sulfur compound with the compound surface.
The particle diameter of the nanometer copper zincium tin sulfur compound is preferably 2 ~ 20 nm.
The biocompatiblity molecules are one kind or many in polyethylene glycol, bovine serum albumin(BSA), chitosan, gelatin
Kind.
It is understood that the biocompatiblity molecules are not limited in above-mentioned molecule, or other it can be received with this
Rice copper zincium tin sulfur compound is combined and has the molecule of biocompatibility.
The copper-zinc-tin-sulfur quaternary nano composite material method with microwave enhanced sensitivity and NMR imaging function is prepared, can be wrapped
Include following steps：
Presoma respectively containing copper, zinc, the presoma of the copper of tin element, the presoma of zinc, tin is dissolved in the first solvent jointly
In, obtain precursor solution A；
The presoma of sulphur containing element sulphur is dissolved in the second solvent, precursor solution B is obtained；
The precursor solution A is heated to after 150 ~ 230 DEG C, the precursor solution B is rapidly injected, both are mutually reciprocal thereafter
Answer 0.5 ~ 5h；After the mixed solution that both constitute is cooled to room temperature, adds after the 3rd solvent and centrifuge, obtain solid matter
Based on nanometer copper zincium tin sulfur compound；
The basic nanometer copper zincium tin sulfur compound is mixed with biocompatiblity molecules, 10 ~ 120min of ultrasound, shakes thereafter thereafter
6 ~ 24h, concussion is centrifuged after terminating, and gained solid matter is the described copper with microwave enhanced sensitivity and NMR imaging function
Zinc-tin sulphur quaternary nano composite material.
Wherein precursor solution A and precursor solution B acquisition can be successively adjusted according to practical situation.
Precursor solution B can be all injected to standard by described be rapidly injected within the time less than 30 ± 10s.
The ultrasonic frequency is 30 ~ 50kHz, and preferably 40kHz, described concussion is preferred to use electric heating constant temperature concussion water
Groove is carried out, and it is 40 ~ 60 Time/min, preferably 50 Time/min that it, which shakes frequency,.
It is understood that in practical operation, on the basis of above-mentioned preparation, implementer can increase some other reinforcing
The step of preparing effect, such as purifying, drying, separating for several times, optimization mixed effect.
The mass ratio of the biocompatiblity molecules and the basic nanometer copper zincium tin sulfur compound is preferably 0.2:1~2:
1。
The presoma of the copper is preferably selected from the one or more in copper chloride, stannous chloride, acetic acid copper liquor；Institute
It is the one or more in zinc chloride, zinc acetate aqueous solution to state the presoma of zinc；The presoma of the tin is selected from chlorination
One or more in tin, the nitric acid tin aqueous solution；The presoma of the sulphur is one kind or many in vulcanized sodium, thiourea solution
Kind.
Second solvent is preferably selected from the one or more in methanol, ethanol, isopropanol, ethylene glycol.
The concentration of the presoma of copper is preferably 40 ~ 60mM, more preferably 50mM, the forerunner of zinc in the precursor solution A
The concentration of body is preferably 20 ~ 40mM, more preferably 30mM, and the concentration of the presoma of tin is preferably 20 ~ 40mM, is more preferably
30mM。
The present invention have the copper-zinc-tin-sulfur quaternary nanocomposite applications of microwave enhanced sensitivity and NMR imaging function in
, can be as photosensitive in the sensitizer in the microwave heat therapeutic of cancer and/or the optical dynamic therapy of cancer when in treatment of cancer
Agent, and/or be further used as in treatment of cancer carry out NMR imaging when contrast agent, it also can be separately as NMR imaging
When contrast agent application.
It can be also used in other treatments and application for meeting its action principle.
In order to illustrate more clearly of the present invention, with reference to embodiment and accompanying drawing, the present invention is described further.This
Art personnel should be appreciated that following specifically described content is illustrative and be not restrictive, and should not be limited with this
Protection scope of the present invention.
The all pure levels of analysis of chemical reagent used in following examples；The water used is deionized water.
Embodiment 1
(1) chlorination that zinc acetate aqueous solution that the acetic acid copper liquor for being 50mM by concentration, concentration are 30mM, concentration are 30mM
The tin aqueous solution is dissolved in 50mL ethylene glycol jointly, stirs, and obtains precursor solution A；
(2) concentration is dissolved in 10mL methanol for 10mM sodium sulfide solution, obtains precursor solution B；
(3) precursor solution A is heated to after 180 DEG C, is rapidly injected precursor solution B, continue to react 2h, question response solution
It is cooled to after room temperature, adds ethanol and centrifuged, collect the lower sediment after centrifugation and drying, obtain basic nanometer copper-zinc-tin-sulfur
Compound；
(4) polyethylene glycol for taking molecular weight to be 0.5 ten thousand is mixed with above-mentioned basic nanometer copper zincium tin sulfur compound, 40 kHz's
Ultrasound 10min under frequency, normal temperature concussion afterwards 12 hours, concussion frequency is 50 Time/min, and polyethylene glycol used is received with basis
The mass ratio of rice copper zincium tin sulfur compound is 1:1, concussion centrifuges washing after terminating, and obtained solid matter is dried, produced
Thing；
Products therefrom is the copper-zinc-tin-sulfur quaternary nano material for the peg molecule modification that particle diameter is 12 ± 2.3 nm, and it is transmitted
Electron microscope（JEOL JEM-2100）As shown in Figure 1, wherein the particle diameter of copper zincium tin sulfur compound is 5 ± 0.6nm；
Products therefrom is configured to different concentration（0.1mg/mL、0.6mg/mL、1.2mg/mL）, and with physiological saline progress pair
Than utilizing microwave therapy apparatus（Model：MH-1Y power：1.8 W frequencies：2450 MHz ）Heating experiment is carried out, its effect that heats up
Fruit as shown in Figure 2, illustrates that it has good microwave temperature rise effect；
Products therefrom is further configured to different concentration（0~2.0mM）, utilize NMR imaging instrument（3.0 T, GE, USA）
T1 imaging tests are carried out, its result as shown in Figure 3, illustrates there is obvious T1 image enhancements function.
Embodiment 2
(1) by copper chloride（50mM）, zinc chloride（30mM）, stannic chloride（30mM）Presoma is dissolved in 50mL ethylene glycol, stirring
Uniformly, precursor solution A is obtained；
(2) by vulcanized sodium（10mM）It is dissolved in 10mL absolute ethyl alcohols, obtains precursor solution B；
(3) precursor solution A is heated to 160 DEG C, is rapidly injected precursor solution B, continue to react 1h, question response solution is cold
But to room temperature, ethanol is added, centrifugation is collected lower sediment and dried, obtains basic nanometer copper zincium tin sulfur compound；
(4) polyethylene glycol for taking molecular weight to be 0.3 ten thousand is mixed with above-mentioned basic nanometer copper zincium tin sulfur compound, is surpassed under 30kHz
Sound 60min, normal temperature concussion thereafter 8 hours, concussion frequency is 40 Time/min, polyethylene glycol used and basic Nanometer Copper zinc-tin
The mass ratio of sulphur compound is 0.2:1, concussion centrifuges washing after terminating, and obtained solid matter is dried, product is obtained；
Product is carried out to transmission electron microscope observing, microwave heating experiment and T1 imaging tests in the way of embodiment 1, it is known that in product
The particle diameter of copper zincium tin sulfur compound is 2 ~ 20 nm, with good microwave temperature rise effect and obvious T1 image enhancements function.
Embodiment 3
（1）By stannous chloride（50mM）, zinc chloride（30mM）, nitric acid tin（30mM）Presoma is dissolved in 50mL ethylene glycol, stirring
Uniformly, precursor solution A is obtained；
(2) by thiocarbamide（10mM）It is dissolved in 10mL methanol, obtains precursor solution B；
(3) precursor solution A is heated to 150 DEG C, is rapidly injected precursor solution B, continue to react 3h, question response solution is cold
But to room temperature, ethanol is added, centrifugation is collected lower sediment and dried, obtains basic nanometer copper zincium tin sulfur compound；
(4) polyethylene glycol for taking molecular weight to be 100,000 is mixed with above-mentioned basic nanometer copper zincium tin sulfur compound, ultrasonic at 50 hz
80min, normal temperature concussion thereafter 6 hours, concussion frequency is 60 Time/min, polyethylene glycol used and basic nanometer copper-zinc-tin-sulfur
The mass ratio of compound is 0.5:1, concussion centrifuges washing after terminating, and obtained solid matter is dried, product is obtained；
Product is carried out to transmission electron microscope observing, microwave heating experiment and T1 imaging tests in the way of embodiment 1, it is known that in product
The particle diameter of copper zincium tin sulfur compound is 2 ~ 20 nm, with good microwave temperature rise effect and obvious T1 image enhancements function.
Embodiment 4
（1）By copper acetate（50mM）, zinc acetate（30mM）, nitric acid tin（30mM）Presoma is dissolved in 50mL ethylene glycol, and stirring is equal
It is even, obtain precursor solution A；
(2) by thiocarbamide（10mM）It is dissolved in 10mL isopropanols, obtains precursor solution B；
(3) precursor solution A is heated to 200 DEG C, is rapidly injected precursor solution B, continue to react 4h, question response solution is cold
But to room temperature, ethanol is added, centrifugation is collected lower sediment and dried, obtains basic nanometer copper zincium tin sulfur compound；
(4) bovine serum albumin(BSA) is taken to be mixed with above-mentioned basic nanometer copper zincium tin sulfur compound, the ultrasound 90min under 30kHz, its
Ice-water bath shakes 3h afterwards, and concussion frequency is 50 Time/min, bovine serum albumin(BSA) used and basic nanometer copper zincium tin sulfur compound
Mass ratio be 1.5:1, concussion centrifuges washing after terminating, and obtained solid matter is dried, product is obtained；
Product is carried out to transmission electron microscope observing, microwave heating experiment and T1 imaging tests in the way of embodiment 1, it is known that in product
The particle diameter of copper zincium tin sulfur compound is 2 ~ 20 nm, with good microwave temperature rise effect and obvious T1 image enhancements function.
Embodiment 5
（1）By stannous chloride（50mM）, zinc acetate（30mM）, nitric acid tin（30mM）Presoma is dissolved in 50mL ethylene glycol, stirring
Uniformly, precursor solution A is obtained；
(2) by vulcanized sodium（10mM）It is dissolved in 10mL absolute ethyl alcohols, obtains precursor solution B；
(3) precursor solution A is heated to 210 DEG C, is rapidly injected precursor solution B, continue to react 5h, question response solution is cold
But to room temperature, ethanol is added, centrifugation is collected lower sediment and dried, obtains basic nanometer copper zincium tin sulfur compound；
(4) bovine serum albumin(BSA) is taken to be mixed with above-mentioned basic nanometer copper zincium tin sulfur compound, ultrasound 120min under 40kHz, thereafter
Ice-water bath shakes 16h, and concussion frequency is 50 Time/min, bovine serum albumin(BSA) used and basic nanometer copper zincium tin sulfur compound
Mass ratio be 2:1, concussion centrifuges washing after terminating, and obtained solid matter is dried, product is obtained；
Product is carried out to transmission electron microscope observing, microwave heating experiment and T1 imaging tests in the way of embodiment 1, it is known that in product
The particle diameter of copper zincium tin sulfur compound is 2 ~ 20 nm, with good microwave temperature rise effect and obvious T1 image enhancements function.
Embodiment 6
（1）By copper acetate（50mM）, zinc chloride（30mM）, stannic chloride（30mM）Presoma is dissolved in 50mL ethylene glycol, and stirring is equal
It is even, obtain precursor solution A；
(2) by vulcanized sodium（10mM）It is dissolved in 10mL ethylene glycol, obtains precursor solution B；
(3) precursor solution A is heated to 170 DEG C, is rapidly injected precursor solution B, continue to react 0.5h, question response solution
Room temperature is cooled to, ethanol is added, centrifugation is collected lower sediment and dried, obtains basic nanometer copper zincium tin sulfur compound；
(4) chitosan is taken to be mixed with above-mentioned basic nanometer copper zincium tin sulfur compound, ultrasonic 100min, the 18h of normal temperature concussion thereafter,
The mass ratio of chitosan used and basic nanometer copper zincium tin sulfur compound is 0.8:1, concussion centrifuges washing after terminating, by what is obtained
Solid matter is dried, and obtains product；
Product is carried out to transmission electron microscope observing, microwave heating experiment and T1 imaging tests in the way of embodiment 1, it is known that in product
The particle diameter of copper zincium tin sulfur compound is 2 ~ 20 nm, with good microwave temperature rise effect and obvious T1 image enhancements function.
Embodiment 7
（1）By copper acetate（50mM）, zinc chloride（30mM）, nitric acid tin（30mM）Presoma is dissolved in 50mL ethylene glycol, and stirring is equal
It is even, obtain precursor solution A；
(2) by thiocarbamide（10mM）It is dissolved in 10mL absolute methanols, obtains precursor solution B；
(3) precursor solution A is heated to 230 DEG C, is rapidly injected precursor solution B, continue to react 2.5h, question response solution
Room temperature is cooled to, ethanol is added, centrifugation is collected lower sediment and dried, obtains basic nanometer copper zincium tin sulfur compound；
(4) take gelatin to be mixed with above-mentioned basic nanometer copper zincium tin sulfur compound, ultrasonic 90min, thereafter normal temperature concussion 20h, it is used
The mass ratio of gelatin and basic nanometer copper zincium tin sulfur compound is 0.4:1, concussion centrifuges washing after terminating, by obtained solids
Matter is dried, and obtains product；
Product is carried out to transmission electron microscope observing, microwave heating experiment and T1 imaging tests in the way of embodiment 1, it is known that in product
The particle diameter of copper zincium tin sulfur compound is 2 ~ 20 nm, with good microwave temperature rise effect and obvious T1 image enhancements function.
Embodiment 8
（1）By copper chloride（50mM）, zinc acetate（30mM）, nitric acid tin（30mM）Presoma is dissolved in 50mL ethylene glycol, and stirring is equal
It is even, obtain precursor solution A；
(2) by vulcanized sodium（10mM）It is dissolved in 10mL isopropanols, obtains precursor solution B；
(3) precursor solution A is heated to 190 DEG C, is rapidly injected precursor solution B, continue to react 1h, question response solution is cold
But to room temperature, ethanol is added, centrifugation is collected lower sediment and dried, obtains basic nanometer copper zincium tin sulfur compound；
(4) chitosan is taken to be mixed with above-mentioned basic nanometer copper zincium tin sulfur compound, ultrasonic 30min shakes thereafter 20h, shell used
The mass ratio of glycan and basic nanometer copper zincium tin sulfur compound is 1.6:1, concussion centrifuges washing after terminating, by obtained solids
Matter is dried, and obtains product；
Product is carried out to transmission electron microscope observing, microwave heating experiment and T1 imaging tests in the way of embodiment 1, it is known that in product
The particle diameter of copper zincium tin sulfur compound is 2 ~ 20 nm, with good microwave temperature rise effect and obvious T1 image enhancements function.
Embodiment 9
（1）By copper chloride（50mM）, zinc acetate（30mM）, stannic chloride（30mM）Presoma is dissolved in 50mL ethylene glycol, and stirring is equal
It is even, obtain precursor solution A；
(2) by thiocarbamide（10mM）It is dissolved in 10mL ethylene glycol, obtains precursor solution B；
(3) precursor solution A is heated to 220 DEG C, is rapidly injected precursor solution B, continue to react 4.5h, question response solution
Room temperature is cooled to, ethanol is added, centrifugation is collected lower sediment and dried, obtains basic nanometer copper zincium tin sulfur compound；
(4) take gelatin to be mixed with above-mentioned basic nanometer copper zincium tin sulfur compound, ultrasonic 20min, thereafter warm water concussion 24h, it is used
The mass ratio of gelatin and basic nanometer copper zincium tin sulfur compound is 1.8:1, concussion centrifuges washing after terminating, by obtained solids
Matter is dried, and obtains product；
Product is carried out to transmission electron microscope observing, microwave heating experiment and T1 imaging tests in the way of embodiment 1, it is known that in product
The particle diameter of copper zincium tin sulfur compound is 2 ~ 20 nm, with good microwave temperature rise effect and obvious T1 image enhancements function.
Embodiment 10
（1）By stannous chloride（50mM）, zinc chloride（30mM）, stannic chloride（30mM）Presoma is dissolved in 50mL ethylene glycol, stirring
Uniformly, precursor solution A is obtained；
(2) by vulcanized sodium（10mM）It is dissolved in 10mL methanol, obtains precursor solution B；
(3) precursor solution A is heated to 195 DEG C, is rapidly injected precursor solution B, continue to react 5h, question response solution is cold
But to room temperature, ethanol is added, centrifugation is collected lower sediment and dried, obtains basic nanometer copper zincium tin sulfur compound；
(4) bovine serum albumin(BSA) is taken to be mixed with above-mentioned basic nanometer copper zincium tin sulfur compound, ultrasonic 30min, thereafter ice-water bath shake
Swing 12h, the mass ratio of bovine serum albumin(BSA) used and basic nanometer copper zincium tin sulfur compound is 0.4:1, concussion is centrifuged after terminating
Washing, obtained solid matter is dried, product is obtained；
Product is carried out to transmission electron microscope observing, microwave heating experiment and T1 imaging tests in the way of embodiment 1, it is known that in product
The particle diameter of copper zincium tin sulfur compound is 2 ~ 20 nm, with good microwave temperature rise effect and obvious T1 image enhancements function.
Embodiment 11
（1）By embodiment 10（1）~（3）The step of prepare comparison copper zincium tin sulfur compound（CZTS）；
（2）By the copper zincium tin sulfur compound and product made from embodiment 10（CZTS-BSA）Carry out cell experiment, including body
Outer cytotoxicity test, the experiment of cell photo-thermal therapy；Hemolysis in vitro is tested；Mouse tumor Experiment on therapy, mouse toxicity experiment and
Active material is tested；
Test result indicates that, the standard mtt assay and dead cell stain living carried out by HePG-2 cells, CZTS and CZTS-BSA has
There is relatively low cytotoxicity；Both are respectively provided with efficient photo-thermal killing ability under near-infrared laser irradiation to cancer cell；It is different dense
The CZTS-BSA of degree hemolysis rate is below 5%, it was demonstrated that it has good blood compatibility, and contrasts, and CZTS is to red blood cell
Film has certain damaging influence；The PTT-CDT therapies that mouse uses are shown, CZTS-BSA is under laser irradiation, tumour table
Face temperature is rapidly increased to 60 DEG C in 5min, and tumour growth is significantly suppressed, and its volume persistently reduces, and in observation
Without rebound phenomenon in phase, and contrast groups without any treatment and the contrast groups that CZTS is individually used in the case of without irradiation, and
The contrast groups only irradiated using laser, its tumor surface is without considerable temperature variation, and gross tumor volume persistently increases, explanation
CZTS-BSA can cooperate with light power link to carry out oncotherapy as a kind of good internal photo-thermal sensitizer；And it is quiet by tail
When the mouse toxicity experiment that arteries and veins injection system is carried out finds CZTS injection volumes for 50mg/kg, mouse starts death, and its dosage reaches
During 200mg/kg, the death rate reaches 100%, and under same dosage and more other dosage tests, CZTS-BSA injection is equal
Mouse will not be caused to occur a death；By using DCFH-DA probe in detecting reactive oxygen species after histocyte culture 4h
The mode of cluster carries out active material test display, and near-infrared laser irradiation can induce CZTS or CZTS-BSA and produce reactive oxygen species
（ROS）, cause histocyte major injury, including mitochondrial dysfunction and ROS dyspoiesises occur, cause powerful cancer thin
Born of the same parents' lethal effect, electron paramagnetic resonance（ERP）Test finds that both can produce abundant hydroxyl radical free radical under irradiation, effectively
For oncotherapy.
Claims (10)
1. the copper-zinc-tin-sulfur quaternary nano composite material with microwave enhanced sensitivity and NMR imaging function, it is characterised in that：The tool
There is the copper-zinc-tin-sulfur quaternary nano composite material of microwave enhanced sensitivity and NMR imaging function comprising nanometer copper zincium tin sulfur compound and be somebody's turn to do
The biocompatiblity molecules of compound surface.
2. according to claim 1 have the nano combined material of the copper-zinc-tin-sulfur quaternary of microwave enhanced sensitivity and NMR imaging function
Material, it is characterised in that：The particle diameter of the nanometer copper zincium tin sulfur compound is 2 ~ 20 nm.
3. according to claim 1 have the nano combined material of the copper-zinc-tin-sulfur quaternary of microwave enhanced sensitivity and NMR imaging function
Material, it is characterised in that：The biocompatiblity molecules are one in polyethylene glycol, bovine serum albumin(BSA), chitosan, gelatin
Plant or a variety of.
4. according to claim 3 have the nano combined material of the copper-zinc-tin-sulfur quaternary of microwave enhanced sensitivity and NMR imaging function
Material, it is characterised in that：The molecular weight polyethylene glycol is 0.3 ~ 100,000；It is preferred that, the molecular weight polyethylene glycol is 0.5 ten thousand.
5. the copper-zinc-tin-sulfur quaternary with microwave enhanced sensitivity and NMR imaging function according to any one of claim 1 ~ 4 is received
The preparation method of nano composite material, it is characterised in that：Comprise the following steps：
Presoma respectively containing copper, zinc, the presoma of the copper of tin element, the presoma of zinc, tin is dissolved in the first solvent jointly
In, obtain precursor solution A；
The presoma of sulphur containing element sulphur is dissolved in the second solvent, precursor solution B is obtained；
The precursor solution A is heated to after 150 ~ 230 DEG C, the precursor solution B is rapidly injected, both are mutually reciprocal thereafter
Answer 0.5 ~ 5h；After the mixed solution that both constitute is cooled to room temperature, adds after the 3rd solvent and centrifuge, obtain solid matter
Based on nanometer copper zincium tin sulfur compound；
The basic nanometer copper zincium tin sulfur compound is mixed with biocompatiblity molecules, 10 ~ 120min of ultrasound, concussion 6 thereafter ~
24h, concussion is centrifuged after terminating, and gained solid matter is the described copper zinc with microwave enhanced sensitivity and NMR imaging function
Tin sulphur quaternary nano composite material.
6. preparation method according to claim 5, it is characterised in that：The biocompatiblity molecules and the basic nanometer
The mass ratio of copper zincium tin sulfur compound is 0.2:1~2:1.
7. preparation method according to claim 5, it is characterised in that：The presoma of the copper is selected from copper chloride, chlorination
One or more in cuprous, acetic acid copper liquor；The presoma of the zinc is one in zinc chloride, zinc acetate aqueous solution
Plant or a variety of；The presoma of the tin is the one or more in stannic chloride, the nitric acid tin aqueous solution；The presoma of the sulphur
For the one or more in vulcanized sodium, thiourea solution.
8. preparation method according to claim 5, it is characterised in that：Second solvent is selected from methanol, ethanol, isopropyl
One or more in alcohol, ethylene glycol.
9. preparation method according to claim 5, it is characterised in that：The concentration of the presoma of the copper is 40 ~ 60mM, excellent
Elect 50mM as, the concentration of the presoma of zinc is 20 ~ 40mM, preferably 30mM, and the concentration of the presoma of tin is 20 ~ 40mM, preferably
For 30mM.
10. the copper-zinc-tin-sulfur quaternary nanometer with microwave enhanced sensitivity and NMR imaging function any one of claim 1 ~ 4
What the preparation method any one of composite or claim 5 ~ 9 was prepared has microwave enhanced sensitivity and NMR imaging work(
The application process of the copper-zinc-tin-sulfur quaternary nano composite material of energy, it is characterised in that：Described will have microwave enhanced sensitivity and nuclear-magnetism into
As the copper-zinc-tin-sulfur quaternary nanocomposite applications of function are in treatment of cancer and/or NMR imaging.
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