CN104548140A - Novel copper-based nano contrast medium for three modes including magnetic resonance imaging, photoacoustic imaging and near infrared thermal imaging and preparation method of novel copper-based nano contrast medium - Google Patents
Novel copper-based nano contrast medium for three modes including magnetic resonance imaging, photoacoustic imaging and near infrared thermal imaging and preparation method of novel copper-based nano contrast medium Download PDFInfo
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Abstract
The invention relates to a novel copper-based nano contrast medium for three modes including magnetic resonance imaging, photoacoustic imaging and near infrared thermal imaging and a preparation method of the novel copper-based nano contrast medium. The nano contrast medium is characterized in that copper sulfide nanocrystalline coated with hydrophobic molecules is taken as a core which is coated with a layer of amphiphilic molecules, the copper sulfide nanocrystalline coated with the hydrophobic molecules adopts a disc structure, and the particle size of the copper sulfide nanocrystalline is 10-30 nm. According to the nano contrast medium, the copper sulfide nanocrystalline has high absorption in a near-infrared position and can be taken as a contrast medium for photoacoustic imaging and near infrared thermal imaging; meanwhile, copper atoms serve as paramagnetic metal ions and can provide a contrast performance for magnetic resonance imaging. The provided nano contrast medium has good multi-mode contrast performance.
Description
Technical field
The invention belongs to technical field of nano material, be specifically related to a kind of novel copper-based magnetic resonance/optoacoustic/near infrared imaging three mode imaging nano-contrast agent and preparation method thereof.
Background technology
Cancer is one of important diseases threatening human health, if in early diagnosis of cancer also treatment in time, then can greatly can improve the life quality of patient and reduce mortality rate.Medical Imaging has indelible effect in the diagnosis of cancer.The imaging technique of current clinical practice comprises nuclear magnetic resonance (MRI) that traditional X-ray, ultrasonic, computer tomography (CT) and development in recent years get up, photoacoustic imaging, single photon emission computerized tomography (SPECT), positron emission tomography (PET) and near infrared imaging etc.
But single molecular image technology also exists some defects self being difficult to overcome, such as in many-sided existence restriction such as Time and place resolution, penetration depth and energy extensibility.Single imaging mode is not enough to obtain tumor information fully, and the associating of multi-modal imaging technology can realize having complementary advantages each other, provides more accurately comprehensively information for clarifying a diagnosis.
But imaging technique conventional at present all uses contrast agent different separately, for obtaining comparatively comprehensively information, often needing to use multiple contrast agent or composite contrast agent simultaneously, this considerably increases the biological safety risk of contrast agent in human body.
The research developing into multi-modal imaging nano-probe of nanotechnology provides good platform, by nano-probe in conjunction with multiple imaging function, is applied to the diagnosis and detection that tumor is early stage.In prior art, the nano-probe in a large number based on nanotechnology is developed, and as quantum dot, magnetic nano-particle, near infrared fluorescent dye and radio-labelled molecule etc., but still not can solve radiography and strengthens the property and the problem of bio-toxicity.
Therefore, develop a kind of there is good biocompatibility and biological safety and have the novel nano contrast agent that multi-modal imaging radiography strengthens the property have very important significance.
Summary of the invention
For above demand, the object of the present invention is to provide a kind of novel copper-based magnetic resonance/optoacoustic/near infrared imaging three mode imaging nano-contrast agent and preparation method thereof.
At this, on the one hand, the invention provides a kind of cuprio magnetic resonance/optoacoustic/near infrared imaging three mode imaging nano-contrast agent, it is brilliant in kernel with the copper sulphide nano wrapped up by hydrophobic molecule, and be wrapped with one deck amphipathic molecule at described kernel, the described copper sulphide nano crystalline substance wrapped up by hydrophobic molecule is disc-shaped structure, and the particle diameter of described copper sulphide nano crystalline substance is 10 ~ 30nm.
In nano-contrast agent of the present invention, copper sulphide nano crystalline substance has strong absorption at near-infrared place, can as photoacoustic imaging and near infrared imaging contrast agent.Meanwhile, because copper atom is as paramagnetic metal ion, nuclear magnetic resonance radiography performance can be provided.Nano-contrast agent provided by the invention has good multi-mode radiography performance.And in nano-contrast agent of the present invention, the particle diameter of copper sulphide nano crystalline substance is 10 ~ 30nm, the little blood circulation time be conducive in body of particle diameter, and passive cogregation efficiency, can excrete out in organism.The existence of amphipathic molecule then overcomes hydrophobicity and the bio-toxicity of copper sulfide itself, gives biocompatibility in the dispersibility of its good phosphate-buffered phosphate buffered solution or normal saline, stability and body.In sum, the present invention adopts single compound nano material can strengthen the radiography performance of nuclear magnetic resonance, photoacoustic imaging and near infrared imaging three mode imaging simultaneously.The good biological safety that this nano-contrast agent has and three pattern radiography performances, can be used for the various diseases especially early discovery of cancer and diagnosis, have application prospect widely in clinical medicine.
Preferably, described hydrophobic molecule is at least one in oleyl amine, ethylenediamine, aniline and nitroaniline.
Preferably, described amphipathic molecule is at least one in phospholipid Polyethylene Glycol, TGA, mercaptoethylmaine, Mercaptoundecanoic acid and mercapto-polyglycol.
Preferably, described phospholipid Polyethylene Glycol is amino-terminated phospholipid Polyethylene Glycol and/or the phospholipid Polyethylene Glycol of methoxy group.
On the other hand, the present invention also provides the preparation method of above-mentioned nano-contrast agent, comprises the steps:
1) hydrophobic organic solvent being dissolved with copper sulfur source presoma is incubated 0.5 ~ 5 minute at 100 ~ 300 DEG C, cooling, solid-liquid separation, the copper sulphide nano obtaining hydrophobic molecule parcel is brilliant;
2) the copper sulphide nano crystalline substance that the hydrophobic molecule obtained is wrapped up is scattered in hydrophobic solvent, adds amphiphilic compound, except desolventizing after stirring;
3) by step 2) product be dissolved in aqueous solution, filter, i.e. obtained described nano-contrast agent.
The present invention adopts single compound (copper sulfur source presoma) simultaneously as sulfur source and copper source presoma, obtains CuS nanocrystalline, and realize the parcel of hydrophobic molecule simultaneously by thermal decomposition method.Preparation technology's simple and fast of the present invention, pollute little, reproducible.And by preparation method of the present invention, the copper sulphide nano that can obtain comparatively small particle diameter (10 ~ 30nm) is brilliant.
Preferably, step 1) in, described copper sulfur source presoma is ethoxy-dithioformic acid copper and/or copper diethyl dithiocarbamate etc., described ethoxy-dithioformic acid copper is prepared by the following method: to be added to by copper salt solution in ethoxy-dithioformic acid potassium solution and to stir, generate the rear solid-liquid separation of precipitation, and dry isolated solid.
Preferably, described mantoquita is copper chloride, copper nitrate, Schweinfurt green and/or copper sulfate etc.
Preferably, step 1) in, the consumption of described hydrophobic organic solvent is: every 1mol copper sulfur source presoma uses 40 ~ 60L.
Preferably, step 3) in, described aqueous solution is phosphate buffer or normal saline.
Preferably, step 1) comprise the steps:
A) at 100 ~ 150 DEG C, noble gas removing oxygen wherein and water are passed into hydrophobic organic solvent, is incubated 15 ~ 30 minutes;
B) described hydrophobic organic solvent be warming up to 200 ~ 300 DEG C and keep 5 ~ 10 minutes, the hydrophobic organic solvent that quick injection is dissolved with copper sulfur source presoma continues reaction 0.5 ~ 5 minute, cooling, solid-liquid separation, the copper sulphide nano obtaining hydrophobic molecule parcel is brilliant.
Accompanying drawing explanation
Fig. 1 is that embodiment 1 obtains copper sulphide nano crystalline substance and is dispersed in transmission electron microscope photo in chloroform and phosphate buffered solution and high resolution electron microscopy photo thereof, wherein a is the transmission electron microscope photo of the copper sulphide nano crystalline substance of oleyl amine parcel, the transmission electron microscope photo of the copper sulphide nano crystalline substance that b phospholipid molecule is modified, c is the SEAD ring of copper sulphide nano crystalline substance, and d is the brilliant high resolution electron microscopy photo of copper sulphide nano;
Fig. 2 is the EDS collection of illustrative plates of the copper sulphide nano crystalline substance that embodiment 1 obtains;
Fig. 3 is the XRD figure spectrum of the copper sulphide nano crystalline substance that embodiment 1 obtains;
Fig. 4 is the brilliant digital photograph be dispersed in chloroform and phosphate buffered solution of copper sulphide nano that embodiment 1 obtains.Wherein a is the brilliant digital photograph be dispersed in chloroform of copper sulphide nano of oleyl amine parcel, and upper strata is chloroform, and lower floor is phosphate buffered solution.B is the digital photograph that the parcel copper sulphide nano crystalline substance of phospholipid is dispersed in phosphate buffered solution;
The DLS particle diameter of the phospholipid parcel after cure copper nanocrystallite that Fig. 5 embodiment 1 is obtained and Zeta potential figure.Wherein, a is grain size distribution, and b is Zeta potential figure;
Fig. 6 is the FTIR collection of illustrative plates of the phospholipid modified front and back of the copper sulphide nano crystalline substance that embodiment 1 obtains.Wherein, a line is that the hydrophobicity copper sulphide nano of oleyl amine parcel is before modified brilliant, and b line is that the hydrophilic copper sulphide nano of modified phospholipid parcel is brilliant;
Fig. 7 is the UV-Vis collection of illustrative plates of the copper sulphide nano crystalline substance that embodiment 1 obtains.Wherein, a is the UV-Vis collection of illustrative plates of the brilliant aqueous solution of variable concentrations copper sulphide nano, and b is the linear graph of the brilliant aqueous solution of variable concentrations copper sulphide nano at summit position absorbance;
Fig. 8 is the external T1 nuclear magnetic resonance imaging signal figure of the copper sulphide nano crystalline substance that embodiment 1 obtains.Wherein, straight line is the brilliant relaxation rate r1 of solution of variable concentrations copper sulphide nano and the linear relationship chart of concentration, and illustration is the T1 nuclear magnetic resonance imaging signal figure of the brilliant solution of water and variable concentrations copper sulphide nano;
Fig. 9 is the external photoacoustic imaging signal graph of the copper sulphide nano crystalline substance that embodiment 1 obtains.Wherein, straight line be the photoacoustic signal value of the brilliant solution of variable concentrations copper sulphide nano under 1064nm laser excitation along with concentration curve, illustration is the photoacoustic signal figure that the brilliant solution of variable concentrations copper sulphide nano is embedded in agar gel;
Figure 10 is the near infrared imaging picture of the copper sulphide nano crystalline substance that embodiment 1 obtains.Wherein, adopt 980nm laser, power density is 0.21W cm
-2near infrared imaging picture under effect.
Detailed description of the invention
Further illustrate the present invention below in conjunction with accompanying drawing and following embodiment, should be understood that accompanying drawing and following embodiment are only for illustration of the present invention, and unrestricted the present invention.
The invention provides a kind of cuprio magnetic resonance/optoacoustic/near infrared imaging three mode imaging nano-contrast agent, brilliant in kernel with hydrophobicity copper sulphide nano, and be wrapped with one deck amphipathic molecule at kernel.Hydrophobic nano copper sulfide can be the copper sulphide nano crystalline substance wrapped up by hydrophobic molecule.Be connected by Van der Waals force between this hydrophobic molecule with amphipathic molecule.Wherein, the particle diameter of copper sulphide nano crystalline substance is disc-shaped structure, and particle diameter is 10 ~ 30nm.The present invention carries out surface modification by amphipathic molecule to copper sulphide nano crystalline substance, makes it have good biocompatibility and biological safety.
Described hydrophobic molecule can be amine, includes but not limited at least one in oleyl amine, ethylenediamine, aniline and nitroaniline.Described amphipathic molecule includes but not limited at least one in phospholipid Polyethylene Glycol, TGA, mercaptoethylmaine, Mercaptoundecanoic acid and mercapto-polyglycol.Wherein phospholipid Polyethylene Glycol is such as with methoxyl group and/or amino-terminated phospholipid peg molecule.In one example, the copper sulphide nano that nano-contrast agent of the present invention wraps up with oleyl amine is brilliant in kernel, the amphipathic phospholipid molecule of core outer wrapping one deck.
The present invention adopts single compound nano material can strengthen the radiography performance of nuclear magnetic resonance, photoacoustic imaging and near infrared imaging three mode imaging simultaneously.The good biological safety that this nano-contrast agent has and three pattern radiography performances.
Nano-contrast agent of the present invention can be prepared by the following method: first sulfur source and copper source presoma are obtained copper sulphide nano crystalline substance by thermal decomposition method in hydrophobic organic solvent, and make hydrophobic organic solvent molecule be wrapped in the surface of copper sulphide nano crystalline substance, thus the copper sulphide nano obtaining being wrapped up by hydrophobic molecule is brilliant simultaneously; And then carry out the parcel of outer amphipathic molecule.
Single compound (copper sulfur source presoma) wherein can be adopted simultaneously as sulfur source and copper source presoma.Copper sulfur source presoma includes but not limited to ethoxy-dithioformic acid copper, copper diethyl dithiocarbamate etc.Ethoxy-dithioformic acid copper can adopt coprecipitation to prepare: to be added to by copper salt solution in ethoxy-dithioformic acid potassium solution and to stir the consumption of mantoquita and the ehtyl potassium xanthate (can stoichiometrically), generates solid-liquid separation after precipitation, and dry isolated solid.Described mantoquita includes but not limited to copper chloride, copper nitrate, Schweinfurt green, copper sulfate etc.The consumption of hydrophobic organic solvent can be: every 1mol ethoxy-dithioformic acid copper uses 40 ~ 60L.Amphipathic molecule and the ratio of the mole of copper sulphide nano crystalline substance wrapped up by hydrophobic molecule can be 2:3 ~ 2:5.
In one example, coprecipitation is first adopted to prepare mantoquita presoma; Then, at 100 ~ 300 DEG C, in amine (combination of one or more in oleyl amine, ethylenediamine, aniline, nitroaniline) solvent, the copper sulphide nano being obtained amine parcel by thermal decomposition method is brilliant; Secondly one deck amphipathic molecule is wrapped up by surface modification at its outer surface, as phospholipid Polyethylene Glycol, sulfhydryl compound (TGA, mercaptoethylmaine, Mercaptoundecanoic acid, mercapto-polyglycol) etc.
In one example, preparation method comprises:
(1) preparation of mantoquita presoma: ehtyl potassium xanthate and copper chloride are dissolved in respectively in water, supersound process makes it dissolve completely, then copper chloride solution is joined in ethoxy-dithioformic acid potassium solution stir, obtain rapidly yellow ethoxy-dithioformic acid copper precipitation.Centrifugalize, vacuum drying;
(2) synthesis of oleyl amine parcel copper sulphide nano crystalline substance: at 100 ~ 150 DEG C, joined in there-necked flask by amine solvent, and the oxygen passed in noble gas removing system and water, be incubated 15 ~ 30 minutes;
System temperature brought up to 200 ~ 300 DEG C and keep 5 ~ 10 minutes, the amine solution injected fast containing above-mentioned ethoxy-dithioformic acid copper continues reaction 30 seconds ~ 5 minutes;
Centrifugalize, the copper sulphide nano namely obtaining oleyl amine parcel is brilliant, is scattered in chloroform, cyclohexane extraction equal solvent;
(3) synthesis of the copper sulphide nano crystalline substance of phospholipid parcel:
In the dispersion liquid of above-mentioned copper sulphide nano crystalline substance, add phospholipid molecule, after stirring at 30 ~ 100 DEG C evaporation of solvent; With phosphate buffer or physiological saline solution, after filtration, obtain the brilliant contrast agent of copper sulphide nano.
Exemplify embodiment below further to describe the present invention in detail.Should understand equally; following examples are only used to further illustrate the present invention; can not be interpreted as limiting the scope of the invention, some nonessential improvement that those skilled in the art's foregoing according to the present invention is made and adjustment all belong to protection scope of the present invention.The technological parameter etc. that following example is concrete is also only an example in OK range, and namely those skilled in the art can be done in suitable scope by explanation herein and select, and do not really want the concrete numerical value being defined in Examples below.
Embodiment 1
The preparation of mantoquita presoma:
Be dissolved in 20mL water respectively by 20mmol (3.21g) ehtyl potassium xanthate and 10mmol (1.705g) copper chloride, ultrasonic disperse, makes it fully dissolve;
Again copper chloride solution is joined in ethoxy-dithioformic acid potassium solution and stirs, generate rapidly yellow ethoxy-dithioformic acid copper precipitation, collected by centrifugation, with water and washing with alcohol several times, then at 50 DEG C, vacuum drying is for subsequent use.
The preparation of oleyl amine parcel hydrophobicity copper sulphide nano crystalline substance:
8mL oleyl amine is joined in 100mL there-necked flask and stirs, and pass into noble gas (N
2, Ar), temperature is elevated to 100 DEG C, keeps this temperature 15min with the water in removing system and oxygen;
Again reaction temperature be elevated to 230 DEG C and keep 15min, then injecting the oleyl amine solution comprising 0.2mmol (0.0621g) ethoxy-dithioformic acid copper fast, after reaction 30s-5min, this reaction solution being injected in 20mL acetone fast and cooling;
Centrifugalize, and with washing with alcohol several times, the hydrophobicity copper sulphide nano obtaining oleyl amine parcel is brilliant, is dispersed in chloroform for subsequent use.
Fig. 1 a is the transmission electron microscope photo that the hydrophobicity copper sulphide nano crystalline substance of oleyl amine parcel prepared by the present embodiment is dispersed in chloroform, and in figure, copper sulphide nano crystalline substance is in the form of annular discs, favorable dispersibility, and particle diameter is about 10-20nm;
Fig. 2 is the EDS collection of illustrative plates of copper sulphide nano crystalline substance prepared by the present embodiment.Element Cu described in figure and S can detect;
Fig. 3 is the XRD figure spectrum of copper sulphide nano crystalline substance prepared by the present embodiment.The crystalline substance of copper sulphide nano described in figure belongs to six side phase Cu
9s
5structure;
Fig. 4 a is the brilliant digital photograph be dispersed in chloroform of copper sulphide nano prepared by the present embodiment.Wherein, in figure, silica dish top solution is the chloroformic solution containing copper sulphide nano crystalline substance, and bottom solution is phosphate buffered solution.Top solution is shown as blackish green;
In Fig. 6, a line is the FTIR collection of illustrative plates of copper sulphide nano crystalline substance prepared by the present embodiment.Oleyl amine main functional group CH2 in figure, the characteristic peak of NH, CN can detect.
The synthesis of the hydrophilic copper sulphide nano crystalline substance of phospholipid parcel:
The amino-terminated phospholipid molecule of 500mg (1,2-distearyl-SN-glycerol-3-phosphatidyl ethanolamine-N-amino-Macrogol 2000, DSPE-PEG is added in the chloroformic solution (5mL) of the hydrophobicity copper sulphide nano crystalline substance wrapped up at above-mentioned oleyl amine
2000-NH
2) and the phospholipid molecule (DSPE-PEG 2000, DSPE-mPEG of 200mg methoxy group
2000), ultrasonic 5min, makes phospholipid molecule dissolve completely;
Remove chloroform in 60 DEG C of evacuation rotary evaporation 1h, obtain the cyan film of one deck;
Add 5mL phosphate buffered solution or the above-mentioned film of physiological saline solution, ultrasonic 5min in ultrasonic pond, film splits away off from bottle wall, obtains cyan aqueous solution;
By the filter membrane of this solution by 0.22 μm, remove large aggregate, finally solution is placed in 4 DEG C of refrigerators and saves backup.
Fig. 1 b is the transmission electron microscope photo that the hydrophilic copper sulphide nano crystalline substance of phospholipid parcel prepared by the present embodiment is dispersed in phosphate buffered solution, in figure copper sulphide nano brilliant through modified pattern and particle diameter without significant change, be still discoid, favorable dispersibility, soilless sticking body;
Fig. 1 c is the SEAD photo of hydrophilic copper sulphide nano crystalline substance prepared by the present embodiment, can find out that prepared copper sulphide nano crystalline substance is polycrystalline structure;
Fig. 1 d is the high-resolution-ration transmission electric-lens photo of hydrophilic copper sulphide nano crystalline substance prepared by the present embodiment;
Fig. 4 b is the digital photograph that the hydrophilic copper sulphide nano crystalline substance of phospholipid parcel prepared by the present embodiment is dispersed in phosphate buffered solution.Solution clear in figure, is shown as shallow blackish green;
Fig. 5 a is the DLS grain size distribution of hydrophilic copper sulphide nano crystalline substance prepared by the present embodiment.The brilliant narrow diameter distribution of copper sulphide nano described in figure, distribution of peaks particle diameter is 16.96nm;
Fig. 5 b is the Zeta potential figure of hydrophilic copper sulphide nano crystalline substance prepared by the present embodiment.Copper sulphide nano described in figure is brilliant positively charged due to the existence of surface amino groups, and current potential is 12.4mV;
In Fig. 6, b line is the FTIR collection of illustrative plates of hydrophilic copper sulphide nano crystalline substance prepared by the present embodiment.With amino-terminated phospholipid DSPE-PEG in figure
2000-NH
2the characteristic absorption peak of main functional group N-C=O can detect;
Fig. 7 a is the UV-Vis collection of illustrative plates of hydrophilic copper sulphide nano crystalline substance prepared by the present embodiment.The crystalline substance of copper sulphide nano described in figure has a wider absorption near infrared light region.Along with concentration increases, absorbance increases;
Fig. 7 b is the brilliant linear graph at summit position absorbance of variable concentrations hydrophilic copper sulphide nano prepared by the present embodiment.Figure neutral line degree of association is 0.99.
Copper sulphide nano is brilliant simultaneously as magnetic resonance/optoacoustic/near infrared imaging three mode imaging contrast agent:
Prepared copper sulphide nano crystalline substance has strong light absorption and photothermal conversion ability near infrared light, can simultaneously as photoacoustic imaging and near infrared imaging contrast agent.Simultaneously due to containing Cu atom as paramagnetic metal ion, can magnetic resonance imaging contrast be used as.
Experimental technique:
T1 NMR (Nuclear Magnetic Resonance)-imaging is tested: aqueous solution copper sulphide nano obtained in embodiment 1 crystalline substance being configured to 6 groups of variable concentrations, detects in the nuclear magnetic resonance analyser of 3.0T.
As shown in Figure 8, obtain T1 NMR (Nuclear Magnetic Resonance)-imaging relaxation rate value is 0.26mM to result
-1s
-1, the content being recorded Cu by ICP is 0.25-4.72mmol/L.
Agar gel photoacoustic imaging: be dissolved in 100mL water by 2g agar, puts into microwave oven and heats 5min.Then in homemade cylinder grinding tool, 2 agar are added, the more brilliant aqueous solution 100uL of the copper sulphide nano adding variable concentrations, and stir, at room temperature natural cooling, obtains the agar gel containing copper sulphide nano crystalline substance.This agar gel is placed on scanning imagery on optoacoustic instrument, and the pulse laser wavelength of employing is 1064nm.
Fig. 9 is the external photoacoustic imaging signal graph of hydrophilic copper sulphide nano crystalline substance prepared by the present embodiment.Figure cathetus be the photoacoustic signal value of the brilliant solution of variable concentrations copper sulphide nano under 1064nm laser excitation along with concentration curve, illustration is the photoacoustic signal figure that the brilliant solution of variable concentrations copper sulphide nano is embedded in agar gel.Along with concentration increases, photoacoustic signal value linearly increases, and the photoacoustic signal brightness of agar gel increases.
Near infrared imaging: water and the brilliant aqueous solution of copper sulphide nano are dropped in sample and covers, from the incident 980nm near-infrared laser of upper vertical, by thermal imaging system record variations in temperature.
Figure 10 is hydrophilic copper sulphide nano crystalline substance (Cu prepared by the present embodiment
2+concentration is 100ppm) and water, at 980nm laser, (power density is 0.21Wcm
-2) irradiate under thermal imaging picture.The brilliant solution of copper sulphide nano described in figure compares water, near infrared imaging effect highly significant.
In sum, copper sulphide nano provided by the invention crystalline substance has good water solublity and stability, blood compatibility and biological safety, to blood and biological tissue organ toxic and side effects little.Due to it, there is strong light absorption and photothermal conversion ability on the one hand, can simultaneously as photoacoustic imaging and near infrared imaging contrast agent.On the other hand, because it contains Cu atom as paramagnetic metal atom, again can as NMR contrast agent.This nanoparticle containing simple function element, as a kind of multifunctional nano contrast agent, significantly can strengthen the radiography performance of nuclear magnetic resonance, NMR/optoacoustic/near infrared imaging multi-modal imaging.This early diagnosis being disease and comprehensive diagnostic provide potential application prospect, are expected to be used widely in tumor or Other diseases diagnosis.
Claims (10)
1. cuprio magnetic resonance/optoacoustic/near infrared imaging three mode imaging nano-contrast agent, it is characterized in that, brilliant in kernel with the copper sulphide nano wrapped up by hydrophobic molecule, and be wrapped with one deck amphipathic molecule at described kernel, the described copper sulphide nano crystalline substance wrapped up by hydrophobic molecule is disc-shaped structure, and the particle diameter of described copper sulphide nano crystalline substance is 10 ~ 30 nm.
2. nano-contrast agent according to claim 1, is characterized in that, described hydrophobic molecule is at least one in oleyl amine, ethylenediamine, aniline and nitroaniline.
3. nano-contrast agent according to claim 1 and 2, is characterized in that, described amphipathic molecule is at least one in phospholipid Polyethylene Glycol, TGA, mercaptoethylmaine, Mercaptoundecanoic acid and mercapto-polyglycol.
4. nano-contrast agent according to claim 3, is characterized in that, described phospholipid Polyethylene Glycol is amino-terminated phospholipid Polyethylene Glycol and/or the phospholipid Polyethylene Glycol of methoxy group.
5. a preparation method for the nano-contrast agent according to any one of Claims 1-4, is characterized in that, comprises the steps:
1) hydrophobic organic solvent being dissolved with copper sulfur source presoma is incubated 0.5 ~ 5 minute at 100 ~ 300 DEG C, cooling, solid-liquid separation, the copper sulphide nano obtaining hydrophobic molecule parcel is brilliant;
2) the copper sulphide nano crystalline substance that the hydrophobic molecule obtained is wrapped up is scattered in hydrophobic solvent, adds amphiphilic compound, except desolventizing after stirring;
3) by step 2) product be dissolved in aqueous solution, filter, i.e. obtained described nano-contrast agent.
6. preparation method according to claim 5, is characterized in that, in step 1), described copper sulfur source presoma is ethoxy-dithioformic acid copper and/or copper diethyl dithiocarbamate
,described ethoxy-dithioformic acid copper is prepared by the following method: to be added to by copper salt solution in ethoxy-dithioformic acid potassium solution and to stir, and generates solid-liquid separation after precipitation, and dry isolated solid.
7. preparation method according to claim 6, is characterized in that, described mantoquita is copper chloride, copper nitrate, Schweinfurt green and/or copper sulfate.
8. the preparation method according to any one of claim 5 to 7, is characterized in that, in step 1), the consumption of described hydrophobic organic solvent is: every 1mol copper sulfur source presoma uses 40 ~ 60L.
9. the preparation method according to any one of claim 5 to 8, is characterized in that, in step 3), described aqueous solution is phosphate buffer or normal saline.
10. the preparation method according to any one of claim 5 to 9, is characterized in that, step 1) comprises the steps:
A) at 100 ~ 150 DEG C, noble gas removing oxygen wherein and water are passed into hydrophobic organic solvent, is incubated 15 ~ 30 minutes;
B) described hydrophobic organic solvent be warming up to 200 ~ 300 DEG C and keep 5 ~ 10 minutes, the hydrophobic organic solvent that quick injection is dissolved with copper sulfur source presoma continues reaction 0.5 ~ 5 minute, cooling, solid-liquid separation, the copper sulphide nano obtaining hydrophobic molecule parcel is brilliant.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109364246A (en) * | 2018-10-11 | 2019-02-22 | 南京鼓楼医院 | Magnetic resonance/activated form fluorescent dual module state imaging targeting photo-thermal diagnosis nano-probe and its synthetic method and application |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012138379A2 (en) * | 2010-10-19 | 2012-10-11 | Board Of Regents, The University Of Texas System | Multifunctional chelator-free radioactive nanoparticles for imaging and therapy |
| CN102961753A (en) * | 2012-12-06 | 2013-03-13 | 东华大学 | Copper sulfide/mesoporous silicon dioxide core-shell nano material as well as preparation method and application thereof |
| CN103936053A (en) * | 2014-04-10 | 2014-07-23 | 厦门大学 | Preparation method of copper sulfide nanowire |
-
2014
- 2014-12-25 CN CN201410838215.0A patent/CN104548140A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012138379A2 (en) * | 2010-10-19 | 2012-10-11 | Board Of Regents, The University Of Texas System | Multifunctional chelator-free radioactive nanoparticles for imaging and therapy |
| CN102961753A (en) * | 2012-12-06 | 2013-03-13 | 东华大学 | Copper sulfide/mesoporous silicon dioxide core-shell nano material as well as preparation method and application thereof |
| CN103936053A (en) * | 2014-04-10 | 2014-07-23 | 厦门大学 | Preparation method of copper sulfide nanowire |
Non-Patent Citations (2)
| Title |
|---|
| MIN ZHOU,ET AL: "Theranostic probe for simultaneous in vivo photoacoustic imaging and confined photothermolysis by pulsed laser at 1064 nm in 4T1 breast cancer model", 《NANOSCALE》 * |
| TIAOXING WEI,ET AL: "Surface-Dependent Localized Surface Plasmon Resonances in CuS Nanodisks", 《ACS APPL. MATER》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109364246A (en) * | 2018-10-11 | 2019-02-22 | 南京鼓楼医院 | Magnetic resonance/activated form fluorescent dual module state imaging targeting photo-thermal diagnosis nano-probe and its synthetic method and application |
| CN109364246B (en) * | 2018-10-11 | 2021-07-09 | 南京鼓楼医院 | Magnetic resonance/activation type fluorescence bimodal imaging targeted photothermal diagnosis and treatment nano probe and synthetic method and application thereof |
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