CN105233307A - Preparation method of small-size rare earth nanogold bioprobe - Google Patents
Preparation method of small-size rare earth nanogold bioprobe Download PDFInfo
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- CN105233307A CN105233307A CN201510683800.2A CN201510683800A CN105233307A CN 105233307 A CN105233307 A CN 105233307A CN 201510683800 A CN201510683800 A CN 201510683800A CN 105233307 A CN105233307 A CN 105233307A
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Abstract
The invention discloses a preparation method of a small-size rare earth nanogold bioprobe. The preparation method includes the steps of stirring rare earth and oleylamine at high temperature for coordination; injecting chloroauric acid, utilizing oleylamine to reduce the chloroauric acid, and allowing gradual nucleating and growing to obtain rare earth nanogold; modifying the rare earth nanogold through polyethylene glycol (PEG) to obtain the rare earth nanogold material high in water solubility and biocompatibility. The preparation method has the advantages of simple experiment process and high repeatability; and the nano material obtained is small in size and high in monodispersity and biocompatibility in water, can be applied in multiple modes of magnetic resonance imaging, CT imaging and photothermal physiotherapy, and can be used in the biomedicine field of imaging in different modes.
Description
Technical field
The present invention relates to a kind of preparation method of nano meter biomaterial, particularly relate to the preparation method of a kind of rare earth nano gold bioprobe, be applied to biomaterial and medical material tech field.
Background technology
In the last few years, Medical Imaging Technology as nuclear magnetic resonance, computer tomography CT imaging etc., clinical medicine detect in obtain great development, this be due to its have highly sensitive, from cell to advantages such as biological tissue's not damaged observations.And the use of contrast agent is absolutely necessary in these image technologies, especially in enhanced ct scans.This is because contrast agent can have the effect of enhancing signal to these image technologies, thus cause the density difference of pathological tissues and normal structure, allow focus " be completely exposed ".But most of contrast agent all only has simple function, such as nanometer Fe
3o
4only has T
2weighted magnetic resonance imaging function; Containing materials such as Ba, Yb, Lu, only there is CT radiography function.If by the size that there is nuclear magnetic resonance, CT imaging function Material cladding can increase nanoparticle, be unfavorable for its metabolism in vivo.Meanwhile, two kinds of functional material compounds certainly can increase experimental procedure, bring difficulty to design of material.
Summary of the invention
In order to solve prior art problem, the object of the invention is to the deficiency overcoming prior art existence, the preparation method of a kind of small size rare earth nano gold bioprobe is provided, obtain that there is undersized multifunctional nano bioprobe, in water good dispersion and biocompatibility good, rare earth nano gold bioprobe prepared by the present invention is applicable to the aspects such as nuclear magnetic resonance, CT imaging and photo-thermal physical therapy, can be used for the biomedical sectors such as the imaging under different mode.
Creating object for reaching foregoing invention, adopting following technical proposals:
A preparation method for small size rare earth nano gold bioprobe, step is as follows:
First, rare earth metal cations solution and oleyl amine are stirred coordination under the high temperature conditions, then gold chloride is injected mixing, utilize oleyl amine to be reduced by gold chloride, and nucleation and growth process obtains rare earth nano gold dispersion liquid gradually, finally by the polyethyleneglycol modified dispersion liquid obtaining rare earth nano gold copper-base alloy.
As the preferred technical scheme of the present invention, the step of the preparation method of small size rare earth nano gold bioprobe is as follows:
A. be solution 30 ~ 60mL and the 5mL oleyl amine mixing of 0.03 ~ 0.06mmol by rare earth metal cations total concentration, be warming up to the yellow solution that 150 ° of C form transparent and homogeneous, obtain the first dispersion liquid, described rare earth metal cations is Gd
3+and Yb
3+in any one or two kinds of ions; The described Gd of preferred employing
3+solution is GdCl
3solution, the described Yb preferably adopted
3+solution is YbCl
3solution;
B. be that 0.3mmol gold chloride 0.118g and 1mL oleyl amine are mixed to get mixed liquor by concentration, then mixed liquor fast injection is entered the first dispersion liquid prepared in described step a, and 90min is maintained under 150 ° of C, then after cooling to room temperature, carry out again centrifugal, washing obtain product, then product is dispersed in chloroform and forms the second dispersion liquid;
C. 10 ~ 30mg Polyethylene Glycol is dissolved in chloroform, add the second dispersion liquid that 2 ~ 4mL is prepared in described step b, and be at room temperature stirred to chloroform evaporate to dryness, add 10mL deionized water again and ultrasonic dissolution, then make gained solution by 0.22mm micropore injection filter membrane, finally obtain rare earth nano gold copper-base alloy aqueous dispersions.
The present invention compared with prior art, has following apparent outstanding substantive distinguishing features and remarkable advantage:
1. the small size rare earth nano gold bioprobe synthetic method of the present invention's employing is simple, repeatability is high, and the rare earth nano gold utensil obtained has good water solublity and biocompatibility;
2. adopt the inventive method to obtain to have the Multifunctional scale cun rare earth nano gold bioprobe of nuclear magnetic resonance, CT imaging and photo-thermal physical therapy simultaneously, compared to Conventional nano radiography material, the technical process of rare earth nano gold bioprobe material prepared by the present invention is simple, repeatability is high, the nano material size obtained is little, in water monodispersity and biocompatibility good, nuclear magnetic resonance, CT imaging, photo-thermal physical therapy multi-mode application can be realized, be expected to be applied to the field of medical biotechnology such as clinical diagnose and targeting diagnosis.
Accompanying drawing explanation
Fig. 1 is the TEM photo of small size rare earth nano gold bioprobe prepared by the embodiment of the present invention one.
Fig. 2 is mice with tumor magnetic resonance imaging contrast figure, wherein scheme A be mice with tumor injection embodiment one prepare small size rare earth nano gold bioprobe before nuclear magnetic resonance figure, and scheme B be mice with tumor tumor locus injection embodiment one prepare small size rare earth nano gold bioprobe after nuclear magnetic resonance figure.
Fig. 3 is mice with tumor CT imaging contrast figure, wherein scheme A be mice with tumor injection embodiment one prepare small size rare earth nano gold bioprobe before CT image, and scheme B be mice with tumor tumor locus injection embodiment one prepare small size rare earth nano gold bioprobe after CT image.
Fig. 4 be the embodiment of the present invention one prepare small size rare earth nano gold bioprobe cell survival rate experimental result picture.
Detailed description of the invention
Details are as follows for the preferred embodiments of the present invention:
embodiment one:
In the present embodiment, see Fig. 1 ~ 4, a kind of step of preparation method of small size rare earth nano gold bioprobe is as follows:
A. be the GdCl of 0.06mmol by rare earth metal cations total concentration
3solution and YbCl
3solution has the mixing of 60mL and 5mL oleyl amine altogether, is warming up to the yellow solution that 150 ° of C form transparent and homogeneous, obtains the first dispersion liquid;
B. be that 0.3mmol gold chloride 0.118g and 1mL oleyl amine are mixed to get mixed liquor by concentration, then mixed liquor fast injection is entered the first dispersion liquid prepared in described step a, and 90min is maintained under 150 ° of C, then after cooling to room temperature, carry out again centrifugal, washing obtain product, then product is dispersed in chloroform and forms the second dispersion liquid;
C. 15mg Polyethylene Glycol is dissolved in chloroform, add the second dispersion liquid that 2mL is prepared in described step b, and be at room temperature stirred to chloroform evaporate to dryness, add 10mL deionized water again and ultrasonic dissolution, then make gained solution by 0.22mm micropore injection filter membrane, finally obtain rare earth nano gold copper-base alloy aqueous dispersions.
experimental test and analysis:
Fig. 1 be the present embodiment prepare gadolinium, ytterbium doping, there is the TEM photo of multifunctional rare-earth nano gold biological probe of nuclear magnetic resonance, CT imaging and photo-thermal physical therapy simultaneously, in FIG, can find out the doping of gadolinium, ytterbium from figure A wherein after, nanometer gold size is less.Figure B is wherein through the modified rare earth nano gold copper-base alloy of PEG, this nano material dispersion homogeneous, do not reunite.Small size nanoparticle is more easily by cell endocytic, and metabolism is very fast in vivo, and this is used as bioprobe to it and circulates significant in vivo.
Fig. 2 is the present embodiment gained sample gadolinium, ytterbium doping while there is the nuclear magnetic resonance figure of multifunctional rare-earth nano gold biological probe of nuclear magnetic resonance, CT imaging and photo-thermal physical therapy.In FIG, figure A is wherein nuclear magnetic resonance figure before mice with tumor injection, and can after tumor locus injects this rare earth nano Au probe from figure B wherein, signal obviously strengthens, and illustrates that small size rare earth nano gold bioprobe material prepared by embodiment can be used for potential magnetic resonance contrast agent.
Fig. 3 is the present embodiment gained sample gadolinium, ytterbium doping while there is the CT image of multifunctional rare-earth nano gold biological probe of nuclear magnetic resonance, CT imaging and photo-thermal physical therapy, figure A is CT image before mice with tumor injection, and can after tumor locus injects this rare earth nano Au probe from figure B, signal obviously strengthens, and illustrates that small size rare earth nano gold bioprobe material prepared by embodiment may be used for potential CT image-forming contrast medium.
Fig. 4 is the present embodiment gained sample gadolinium, ytterbium doping while there is the cell survival rate figure of multifunctional nano gold bioprobe of nuclear magnetic resonance, CT imaging and photo-thermal physical therapy.Even if be 400mg × mL at maximum concentration as can be seen from Fig.
-1time, overt toxicity is not had to cell yet, illustrates that this nano-probe has good biocompatibility.
According to the present embodiment rare earth nano gold bioprobe material preparation method, the product obtained not only size is little, and has the advantages such as multi-modal imaging simultaneously, and particularly gained nano material can be applicable to nuclear magnetic resonance, CT imaging and photo-thermal physical therapy.And this its surface can functionalization further, can be applicable to the field such as clinical diagnose and targeting diagnosis.
In the present embodiment, first, rare earth and oleyl amine are stirred coordination under the high temperature conditions, then by gold chloride inject, utilize oleyl amine by gold chloride reduction and gradually nucleation and growth process obtain nanometer gold.Modify finally by Polyethylene Glycol (PEG) and obtain the rare earth nano gold copper-base alloy with good aqueous solubility and biocompatibility.The inventive method has the advantage that experimentation is simple, repeatability is high, the nano material size obtained is little, in water monodispersity and biocompatibility good, there is the multi-mode application of nuclear magnetic resonance, CT imaging and photo-thermal physical therapy simultaneously, can be used for the biomedical sectors such as the imaging under different mode.
embodiment two:
The present embodiment is substantially identical with embodiment one, and special feature is:
In the present embodiment, a kind of step of preparation method of small size rare earth nano gold bioprobe is as follows:
A. be the GdCl of 0.03mmol by rare earth metal cations concentration
3solution 30mL mixes with 5mL oleyl amine, is warming up to the yellow solution that 150 ° of C form transparent and homogeneous, obtains the first dispersion liquid;
B. be that 0.3mmol gold chloride 0.118g and 1mL oleyl amine are mixed to get mixed liquor by concentration, then mixed liquor fast injection is entered the first dispersion liquid prepared in described step a, and 90min is maintained under 150 ° of C, then after cooling to room temperature, carry out again centrifugal, washing obtain product, then product is dispersed in chloroform and forms the second dispersion liquid;
C. 15mg Polyethylene Glycol is dissolved in chloroform, add the second dispersion liquid that 2mL is prepared in described step b, and be at room temperature stirred to chloroform evaporate to dryness, add 10mL deionized water again and ultrasonic dissolution, then make gained solution by 0.22mm micropore injection filter membrane, finally obtain rare earth nano gold copper-base alloy aqueous dispersions.
embodiment three:
The present embodiment and previous embodiment are substantially identical, and special feature is:
In the present embodiment, a kind of step of preparation method of small size rare earth nano gold bioprobe is as follows:
A. be the YbCl of 0.03mmol by rare earth metal cations concentration
3solution 30mL mixes with 5mL oleyl amine, is warming up to the yellow solution that 150 ° of C form transparent and homogeneous, obtains the first dispersion liquid;
B. be that 0.3mmol gold chloride 0.118g and 1mL oleyl amine are mixed to get mixed liquor by concentration, then mixed liquor fast injection is entered the first dispersion liquid prepared in described step a, and 90min is maintained under 150 ° of C, then after cooling to room temperature, carry out again centrifugal, washing obtain product, then product is dispersed in chloroform and forms the second dispersion liquid;
C. 15mg Polyethylene Glycol is dissolved in chloroform, add the second dispersion liquid that 2mL is prepared in described step b, and be at room temperature stirred to chloroform evaporate to dryness, add 10mL deionized water again and ultrasonic dissolution, then make gained solution by 0.22mm micropore injection filter membrane, finally obtain rare earth nano gold copper-base alloy aqueous dispersions.
By reference to the accompanying drawings the embodiment of the present invention is illustrated above; but the invention is not restricted to above-described embodiment; multiple change can also be made according to the object of innovation and creation of the present invention; change, the modification made under all spirit according to technical solution of the present invention and principle, substitute, combination or simplify; all should be the substitute mode of equivalence; as long as goal of the invention according to the invention; only otherwise deviate from know-why and the inventive concept of the preparation method of small size rare earth nano of the present invention gold bioprobe, all protection scope of the present invention is belonged to.
Claims (3)
1. a preparation method for small size rare earth nano gold bioprobe, it is characterized in that, step is as follows:
First, rare earth metal cations solution and oleyl amine are stirred coordination under the high temperature conditions, then gold chloride is injected mixing, utilize oleyl amine to be reduced by gold chloride, and nucleation and growth process obtains rare earth nano gold dispersion liquid gradually, finally by the polyethyleneglycol modified dispersion liquid obtaining rare earth nano gold copper-base alloy.
2. according to claim 1 small size rare earth nano gold bioprobe preparation method, it is characterized in that, step is as follows:
A. be solution 30 ~ 60mL and the 5mL oleyl amine mixing of 0.03 ~ 0.06mmol by rare earth metal cations total concentration, be warming up to the yellow solution that 150 ° of C form transparent and homogeneous, obtain the first dispersion liquid, described rare earth metal cations is Gd
3+and Yb
3+in any one or two kinds of ions;
B. be that 0.3mmol gold chloride 0.118g and 1mL oleyl amine are mixed to get mixed liquor by concentration, then mixed liquor fast injection is entered the first dispersion liquid prepared in described step a, and 90min is maintained under 150 ° of C, then after cooling to room temperature, carry out again centrifugal, washing obtain product, then product is dispersed in chloroform and forms the second dispersion liquid;
C. 10 ~ 30mg Polyethylene Glycol is dissolved in chloroform, add the second dispersion liquid that 2 ~ 4mL is prepared in described step b, and be at room temperature stirred to chloroform evaporate to dryness, add 10mL deionized water again and ultrasonic dissolution, then make gained solution by 0.22mm micropore injection filter membrane, finally obtain rare earth nano gold copper-base alloy aqueous dispersions.
3. according to claim 2 small size rare earth nano gold bioprobe preparation method, it is characterized in that: in described step a, the described Gd of employing
3+solution is GdCl
3solution, the described Yb of employing
3+solution is YbCl
3solution.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106075443A (en) * | 2016-07-15 | 2016-11-09 | 上海工程技术大学 | A kind of gold cladding copper selenide nanoparticles and preparation method and application |
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| CN102127444A (en) * | 2010-12-10 | 2011-07-20 | 吉林大学 | Nanogold modified enhanced up-conversion luminescence composite material and preparation method thereof |
| WO2014207490A1 (en) * | 2013-06-28 | 2014-12-31 | Bbs Nanotechnology Ltd. | Tumorspecific spect/mr(t1), spect/mr(t2) and spect/ct contrast agents |
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| CN102127444A (en) * | 2010-12-10 | 2011-07-20 | 吉林大学 | Nanogold modified enhanced up-conversion luminescence composite material and preparation method thereof |
| WO2014207490A1 (en) * | 2013-06-28 | 2014-12-31 | Bbs Nanotechnology Ltd. | Tumorspecific spect/mr(t1), spect/mr(t2) and spect/ct contrast agents |
Non-Patent Citations (2)
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106075443A (en) * | 2016-07-15 | 2016-11-09 | 上海工程技术大学 | A kind of gold cladding copper selenide nanoparticles and preparation method and application |
| CN106075443B (en) * | 2016-07-15 | 2019-05-24 | 上海工程技术大学 | A kind of gold cladding copper selenide nanoparticles and the preparation method and application thereof |
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