CN107899023A - A kind of nano-contrast agent and preparation method thereof - Google Patents
A kind of nano-contrast agent and preparation method thereof Download PDFInfo
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- CN107899023A CN107899023A CN201711467382.9A CN201711467382A CN107899023A CN 107899023 A CN107899023 A CN 107899023A CN 201711467382 A CN201711467382 A CN 201711467382A CN 107899023 A CN107899023 A CN 107899023A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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Abstract
The invention belongs to imaging method technical field, discloses a kind of nano-contrast agent and preparation method thereof, and the preparation method of the nano-contrast agent comprises the following steps：The blue tungsten oxide nano particle that particle diameter is 60nm has been synthesized using hydro-thermal method, has been uniformly dispersed in water, the suspension of synthesis；A series of iodine of various concentrations and the solution of tungsten are configured using Iohexol and tungsten oxide nanoparticles, imaging is detected to it using CT.The present invention discloses the targeting of WO3 X@PEG Tf, compare the difference of endocytosis targeted oxidative tungsten nano particle between normal cell and cancer cell and the distribution in tumor-bearing rat and rat body, illustrating WO3 X PEG Tf can be by cancer cell (surface has abundant Tf acceptors) highly single-minded identification, and proves the advantage of transferrins covalent modification.Disclose SPECT/CT imagings and the biocompatibility of WO3 X@PEG Tf.
Description
Technical field
The invention belongs to imaging method technical field, more particularly to a kind of nano-contrast agent and preparation method thereof.
Background technology
The a great problem that cancer is the whole world is captured, successful treating cancer mainly faces 4 problems, that is, makes a definite diagnosis later, easy
In transfer, serious multidrug resistance and easily recurrence etc..The early diagnosis of cancer is the discovery that the key of successful treatment, and selection is optimal
, most sensitive diagnostic means；Strong foundation can be provided for judgement of the doctor to the state of an illness.Currently used Tomographic Diagnosis Technology
Analysis mainly includes：Magnetic resonance imaging, fluorescence imaging, ultrasonic imaging and radionuclide imaging etc..It may be selected according to demand not
With imaging technique live body different parts are carried out with detection in real time in place, makes every effort to reach most clear, accurately image, is pathological diagnosis
Reliable foundation is provided.Fusion of imaging technology (Fusion) can be by CT anatomical structures image and nuclear medicine SPECT functional metabolism shadows
Sound is superimposed.Be conducive to lesion positioning and etiologic diagnosis；In order to obtain clearer, accurately pathology in actually detected
Modified-image, nuclear medicine molecular imaging are one kind of molecular image technology, it molecular medicine fundamental analysis can be obtained into
Fruit is applied directly in clinic using the preclinical phase analysis of molecular image technology.
With the development of molecular image technology, the SPECT/CT technologies that various modes medical image imaging technique combines are had
A degree of development.SPECT/CT is the equipment by high-end SPECT and being combined into one of multi-slices CT, is not only provided
The functional image of SPECT, and the anatomical visualization of CT is provided, improve tradition positioning, qualitatively accuracy.But due to SPECT/
CT acquisition parameters are mostly low milliampere in CT, while CT dose of radiations are reduced, the quality of CT images also have it is different degrees of under
Drop.The common method for reducing dose of radiation is to reduce tube current, the tube voltage of X-ray tube.When tube current is constant, tube voltage from
120kV, which is down to 80kV, can reduce by 70% dose of radiation, obtain the diagnostic message of maximum with minimum dose of radiation as far as possible,
The principle that dose of radiation minimizes is brought up to professional ethics, the height of patient, self-responsibility is recognized, it is ensured that Ge Xiangji
The high quality of art operation；The relation between low-dose scanning and picture quality is how balanced, reduces dose of radiation to greatest extent
Good picture quality is kept as far as possible to meet that diagnostic requirements are the tasks that nucleus medical image needs most concern and completion.It is auxiliary
Help and shown using some nano-contrast agents to carry out enhancing to detection position.The generally preferred ultrasonic imaging inspection of diagnosis for liver cancer
Survey, but unstable tissue attenuation is produced in adiposis patient, the scope of relative small size is difficult to observe, therefore to early stage
Diagnosing cancer of liver be easy to cause mistaken diagnosis；Magnetic resonance imaging can also be used for the diagnosis of liver cancer, but due to its higher testing cost
And using less in the Hepatocarcinoma screening of early stage.The nano-contrast agent often used for common CT imagings is mostly organic iodine small molecule
(such as：Amidotrizoic acid, Iohexol etc.), these micromolecular compounds have short circulation time in vivo, whole body distribution, do not possess targeting
Property, removed by kidney the shortcomings of make contrast time short rapidly, in addition iodine has kidney toxicity, and X-ray can induce iodine thing
The iodine particle that matter ionizes out causes stronger toxicity；Idodine conduct cannot be used to the patient (such as thyroid gland patient) of idodine allergy
The nano-contrast agent of CT.And for often using radioactive element (such as 99mTc, 131I) to be used as nano-contrast agent in SPECT/CT,
Gamma-rays is detected, and damage is also higher than CT bigger, the expense of generation caused by human body.
In conclusion problem existing in the prior art is：An important factor for early diagnosis of tumour is successful treatment tumour
One of, clinically, CT imaging diagnosis are common detection means, and CT nano-contrast agents used in the clinical diagnosis of tumour are mostly to have
Machine iodine small molecule, there are short, the strong renal toxicity of circulation time in vivo and to limitations such as iodine allergy person disablings.
The content of the invention
In view of the problems of the existing technology, the present invention provides a kind of nano-contrast agent and preparation method thereof.
The present invention is achieved in that the preparation method of the nano-contrast agent comprises the following steps：Closed using hydro-thermal method
Into the blue tungsten oxide nano particle that particle diameter is 60nm, it is uniformly dispersed in water, the suspension of synthesis；
A series of iodine of various concentrations and the solution of tungsten are configured using Iohexol and tungsten oxide nanoparticles, using CT to it
Detection imaging.
The solution concentration of iodine is 0-220mmol/L；
The solution concentration of tungsten is 0-150mmol/L.
The nano-contrast agent prepared another object of the present invention is to provide a kind of preparation method such as nano-contrast agent, should
Nano-contrast agent selects novel oxidized tungsten base nano-probe as CT nano-contrast agents, the height identified using TfR
Specificity, reaches targeting；And then the pathological change of targeting moiety is inquired into, illustrate the effect of Accurate Diagnosis.
Advantages of the present invention and good effect are：
The early diagnosis of cancer is the discovery that the key of successful treatment, and nano-contrast agent replaces molecule nano contrast agent to improve
The sensitivity of diagnosis and the clarity of image are imaged in cancer targeting detection, makes it possible that the early stage of cancer makes a definite diagnosis, tungsten and iodine
Compared to the atomic radius with bigger and stronger to X-ray absorption coefficient.The nanometer tungsten oxide that this analysis is synthesized with hydro-thermal method,
Bridging is done with polyethylene glycol, it is SPECT/CT nano-radiographies to be covalently attached the tungsten oxide base nano particle that transferrins is prepared
Agent, using Human normal hepatocyte L-02 and hepatocellular carcinoma H22 as contrast model, with laser confocal microscope, fluidic cell
The transporting mechanism from cell to nano target system and the analysis of the biological effect to cell respectively of the technologies such as instrument, discloses nano-radiography
The targeting of agent；Using rat as model, by being injected intravenously tungsten oxide base nano particle, its internal CT imagings, tissue is analyzed
Distribution and blood biochemistry index measure its biocompatibility；Using tumor-bearing mice as model, pass through CT imaging tracking tungsten oxide bases
The internal targeting of nano particle, experimental basis is provided for the early diagnosis of tumour, is the clinical practice of targeted nano contrast agent
And theoretical and experiment basis are established in exploitation, the in-depth analysis for cancer target diagnosis provides new approaches, new way.It will be tungsten oxide
Theoretical and experimental basis is established in the clinical practice and exploitation of nano particle CT imagings, and the in-depth analysis for nano-contrast agent imaging carries
For new approaches and new way.
(1) targeting of WO3-X@PEG-Tf is disclosed
Compare between normal cell and cancer cell the difference of endocytosis targeted oxidative tungsten nano particle and tumor-bearing mice and big
Distribution in mouse body, illustrate WO3-X PEG-Tf can by the highly single-minded identification of cancer cell (surface have abundant Tf acceptors), and
Prove the advantage of transferrins covalent modification.
(2) SPECT/CT imagings and the biocompatibility of WO3-X@PEG-Tf is disclosed
Influence of the cytotoxicity and nano particle of mtt assay measure nano particle to the blood of rat and tissue, in vivo
Metabolism etc. evaluate the biocompatibility of WO3-X PEG-Tf, using CT imagings compare nano particle and organic iodine reagent into
As rate, and prove advantage of the nano particle in terms of CT imagings respectively.
Brief description of the drawings
Fig. 1 is the SPECT/CT imaging diagnostic analysis schematic diagrams of tungsten oxide base nano particle provided in an embodiment of the present invention；
Fig. 2 is CT imagings (tube voltage 80kV, the pipe electricity of Iohexol and tungsten oxide nanoparticles provided in an embodiment of the present invention
Flow 100mA)；
Fig. 3 is relation (tube voltage 80kV, the tube current between the concentration and CT values of iodine and tungsten provided in an embodiment of the present invention
100mA)；
Fig. 4 is the CT values of tungsten oxide nanoparticles under different tube voltages provided in an embodiment of the present invention；
Fig. 5 is CT image of the tungsten oxide nanoparticles provided in an embodiment of the present invention in pork liver.
Embodiment
In order to make the purpose , technical scheme and advantage of the present invention be clearer, with reference to embodiments, to the present invention
It is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to
Limit the present invention.
Below in conjunction with the accompanying drawings and specific embodiment is further described the application principle of the present invention.
The tungsten oxide nanoparticles (WO3-X) for being adapted to biologic applications particle diameter (10~100nm) are prepared using hydro-thermal method.Selection
Transferrins (Tf) is targeted molecular, by polyethylene glycol (PEG) covalent modification to tungsten oxide nanoparticles.With people's normal hepatocytes
The Bel7402 (HepG2) of cell line (L-02) and the high expression of TfR is external contrast model, carries out nanometer
Cell traffic mechanism and the biological effect analysis of particle, and by comparing the tungsten oxide nanoparticles of endocytosis Surface-modified by Transferrin
Difference between normal cell and cancer cell, discloses the targeting of novel nano tungsten oxide probe system；It is small using lotus knurl at the same time
Mouse is In vivo model, the CT imagings of analysis novel nano oxidation tungsten tipped probe, discloses the tungsten oxide nanometer of transferrins covalent modification
Probe is imaged the superiority in diagnosing tumour in CT.
The analysis of the target cell membrane transporting mechanism of tungsten oxide base nano particle
Using nanometer tungsten oxide-polyethylene glycol-transferrins (WO3-X@PEG-Tf) nano particle of preparation as material, carry out
The analysis of transporting mechanism is targeted, and verifies the advantage of covalent coupling transferrins.
(1) targets identification of cell is acted on
(2) cell traffic mechanism and positioning analysis
(3) difference analysis that nano particle covalent coupling gulps down in the cell with physical absorption transferrins
The biological effect of nano particle and cytosis is analyzed
Selecting nano particle WO3-X@PEG-Tf, WO3-X@- Tf, WO3-X@BSA, (tungsten oxide adsorbs the nanometer of albumin
Grain) and independent WO3-X be related control, carry out the analysis to cytosis effect.
(1) to the influence of cytoactive, form
(2) to the influence of Apoptosis and cycle
(3) to the influence of desmoenzyme and reactive oxygen species
The internal CT imaging trackings of nano particle and the analysis of biocompatibility
It is related control by nano particle WO3-X@PEG-Tf, WO3-X@- Tf, WO3-X@BSA and independent WO3-X, respectively
In tail vein injection rat body, carry out the CT imagings and biocompatibility analysis of nano-probe in rat body.
Nano particle is compared with the CT imagings of common organic iodine (such as Iohexol)
Distribution and metabolism of the nano particle in tumor-bearing rat body, the analysis of internal CT imagings
Influence of the nano particle to rat blood system and tissue
HepG2 cells are injected in Mice Body to the model for establishing tumor-bearing mice, by nano particle WO3-X PEG-Tf and list
Only WO3-X is related control, by tail vein injection and tumor locus locating injection two ways injection model Mice Body, leading to
The targeting positioning tumor of CT imaging analysis tungsten oxide nanoparticles is crossed, and experimental basis is provided for the early diagnosis of tumour.
By selecting novel oxidized tungsten base nano-probe to be used as CT nano-contrast agents, the height of TfR identification is utilized
Specificity is spent, reaches targeting；And then the pathological change of targeting moiety is inquired into, illustrate the effect of Accurate Diagnosis.Therefore target is used
To tungsten oxide base nano particle as SPECT/CT nano-contrast agents for tumour early diagnosis be the present invention innovation.
By to the cell traffic mechanism of nano-contrast agent and the analysis of biological effect, illustrating nano-contrast agent WO3-X@
PEG-Tf has the function of CT imaging diagnosing tumours.
1st, the preparation of tungsten oxide base nano particle
The blue tungsten oxide nano particle that particle diameter is 60nm has been synthesized using hydro-thermal method, can be uniformly dispersed in water.Close
Into suspension it is as shown in Figure 1.
2nd, the CT imagings of tungsten oxide nanoparticles
A series of iodine of various concentrations and the solution (being shown in Table 1) of tungsten are configured using Iohexol and tungsten oxide nanoparticles, is made
Imaging (as shown in Figure 2) is detected to it with CT, the results showed that compared with Iohexol, tungsten oxide nanoparticles equally have X-ray
There are stronger absorption and damping capacity.The CT values of Iohexol and tungsten oxide nanoparticles under various concentrations are compared at the same time, as a result
As shown in figure 3, show that the CT values of tungsten and iodine are in a linear relationship with concentration.It is at the same time 100mA in fixed tube current, changes pipe electricity
Pressure (80,100,120kV) measures the CT values of tungsten oxide nanoparticles, and the results are shown in Figure 4, with the reduction of tube voltage, oxygen
Change the CT values increase of tungsten nano particle, show that tungsten oxide nanoparticles are more advantageous to improving its sensitivity under low tube voltage, carry
The resolution and clarity of hi-vision.In addition absorption of the human body to X-ray can be reduced by reducing tube voltage, so as to reduce human body to X
The radioactive exposure of ray.
The concentration of 1. iodine of table and tungsten
3rd, the CT imagings of tungsten oxide nanoparticles in the tissue
Commercially available pork liver is chosen as tissue model, tungsten oxide nanoparticles suspension the portal vein is injected in liver, is put
CT imagings are carried out in SPECT/CT, the results are shown in Figure 5.Show that tungsten oxide nanoparticles have preferable CT imagings in liver
Function, can be imaged blood vessel as nano-contrast agent.
With the Bel7402 (HepG2) of high expression TfR for external model, Human normal hepatocyte system (L-
02) it is control, analyzes the targeting to tumour with the tungsten oxide nanoparticles of Surface-modified by Transferrin；Established with tumor-bearing mice internal
Model, is injected directly into tumor locus by tungsten oxide base nano particle and tail vein injection two ways carries out CT imaging diagnosis point
Analysis, while biological assessment is carried out to the vivo biodistribution metabolism of tungsten oxide base nano particle and toxicity.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
All any modification, equivalent and improvement made within refreshing and principle etc., should all be included in the protection scope of the present invention.
Claims (3)
1. a kind of preparation method of nano-contrast agent, it is characterised in that the preparation method of the nano-contrast agent includes following step
Suddenly：Using hydro-thermal method synthesized particle diameter be 60nm blue tungsten oxide nano particle, be uniformly dispersed in water, synthesis it is suspended
Liquid；
A series of iodine of various concentrations and the solution of tungsten are configured using Iohexol and tungsten oxide nanoparticles, it is detected using CT
Imaging.
2. the preparation method of nano-contrast agent as claimed in claim 1, it is characterised in that the solution concentration of iodine is 0-220mmol/
L；
The solution concentration of tungsten is 0-150mmol/L.
3. nano-contrast agent prepared by a kind of preparation method of nano-contrast agent as claimed in claim 1, it is characterised in that this is received
Rice contrast agent selects novel oxidized tungsten base nano-probe, and as CT nano-contrast agents, the height identified using TfR is special
One property, reaches targeting.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110507829A (en) * | 2019-07-31 | 2019-11-29 | 湖北大学 | The preparation method and applications of ferrotungsten composite oxide nano-crystal cluster |
| CN114728084A (en) * | 2019-11-29 | 2022-07-08 | 西门子医疗有限公司 | Simultaneous image display of two different functional areas |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101732733A (en) * | 2009-12-24 | 2010-06-16 | 厦门大学 | CT imaging contrast agent and preparation method thereof |
-
2017
- 2017-12-28 CN CN201711467382.9A patent/CN107899023A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101732733A (en) * | 2009-12-24 | 2010-06-16 | 厦门大学 | CT imaging contrast agent and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 宋旭春等: "氧化钨纳米颗粒和纳米线的选择合成及光致发光研究", 《稀有金属材料与工程》 * |
| 闫伟等: "氧化钨（WO3-X@BSA）纳米颗粒的CT成像", 《中国医学影像技术》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110507829A (en) * | 2019-07-31 | 2019-11-29 | 湖北大学 | The preparation method and applications of ferrotungsten composite oxide nano-crystal cluster |
| CN114728084A (en) * | 2019-11-29 | 2022-07-08 | 西门子医疗有限公司 | Simultaneous image display of two different functional areas |
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Application publication date: 20180413 |