CN104208685B - A kind of hollow Ions in nanocrystalline zirconia with tumor microwave heat treatment and CT imaging function and its preparation method and application - Google Patents
A kind of hollow Ions in nanocrystalline zirconia with tumor microwave heat treatment and CT imaging function and its preparation method and application Download PDFInfo
- Publication number
- CN104208685B CN104208685B CN201410453049.2A CN201410453049A CN104208685B CN 104208685 B CN104208685 B CN 104208685B CN 201410453049 A CN201410453049 A CN 201410453049A CN 104208685 B CN104208685 B CN 104208685B
- Authority
- CN
- China
- Prior art keywords
- methylimidazole
- hollow
- ions
- nanocrystalline zirconia
- tumor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention discloses a kind of multi-functional hollow Ions in nanocrystalline zirconia with tumor microwave heat treatment and CT imaging function, and this hollow nano-material a diameter of 50～1000nm, shell thickness is 10～500nm.Multi-functional hollow Ions in nanocrystalline zirconia particle diameter narrow distribution, shell thickness prepared by the present invention and size is controlled, be respectively provided with good dispersibility with ethanol in water.Hollow Ions in nanocrystalline zirconia is applied simultaneously to tumor microwave heat treatment and CT technical field of imaging by the present invention first, achieve good treatment and imaging effect, substantially increase diagnoses and treatment efficiency, the target of diagnosis and treatment integration can be realized simultaneously, there is good clinical value.
Description
Technical field
The present invention relates to hollow zirconium dioxide nanotechnology and biologic applications field thereof.More particularly, to one
Plant and there is tumor microwave heat treatment and the multi-functional hollow Ions in nanocrystalline zirconia of CT imaging function and preparation thereof
Methods and applications.
Background technology
At present, worldwide cancer morbidity allows of no optimist still in ascent stage, cancer present situation
(Nanoscale,2012,4,330-342,Nanoscale,2013,5,12409-12424).The whole world in 2013
New cancer number is more than 1,400 ten thousand, it is contemplated that will rise to more than 20,000,000 to the year two thousand thirty.For China,
The whole nation just has a people to be diagnosed as cancer in every 6 minutes, has every day 8550 people to become cancer patient, there are about 22%
People suffer from cancer, every 7～8 people just have a people to die from cancer, accumulative rate (0～74 years old) is that China occupies
The people are 12.94% because of the probability that cancer is dead.For various reasons, coming 10 years, the cancer morbidity of China
With mortality rate, continuation is risen.Expecting the year two thousand twenty, the annual cancer mortality sum of China will reach 3,000,000
About people, ill sum will reach 6,600,000 people.
Therefore, cancer remains a serious problem threatening human health within decades in the future, to society
Meeting, family and individual bring huge burden and misery.Conventional anti-cancer therapies mainly by chemotherapy,
Radiotherapy, operation etc. are carried out, and rather can bring certain painful and side effect, therefore, science skill to patient
Progressively development and nanotechnology the most perfect of art, brings new opportunity for cancer diagnosis treatment.Make
For the heating of a kind of non-invasion and attack formula local, microwave heat therapeutic technology have noinvasive or Wicresoft, safety preferably, phase
Pass organization internal heating-up temperature is higher, ablated volume is bigger, melts the time faster more equal with heat flux distribution
Even advantage, gradually causes everybody concern in the treatment of tumor.The mechanism of microwave heat therapeutic is to utilize microwave
Heat effect carry out the thermotherapy of tumor.When microwave enters biological tissue, transmission and the energy of microwave can be produced
The absorption of amount, thus in tissue, form certain temperature raise.When temperature reaches more than 43 DEG C, can
To effectively kill tumor cell, so realize thermotherapy purpose (Cardiovasc.Inter.Rad.2010,33
(4),818-827,Phys.Med.Biol.2012,57(8),2309-2327,Nat.Rev.Drug.Discov.
2010,615-27)。
The United States Patent (USP) of Patent No. US20110034916A1, discloses one and can be used for tumor microwave heat
The preparation method and application of the magnetic nanoparticle treated；Patent No. US005330518A and Patent No.
The United States Patent (USP) of US005861021A, also discloses that the application in oncotherapy of the microwave heat therapeutic technology, and
Achieve good therapeutic effect.But it is micro-that the ionic liquid with microwave enhanced sensitivity performance is applied to tumor
Ripple thermotherapy field have not been reported.
CT imaging technique, as the medical imaging diagnostic means of a kind of maturation, has that scanning speed is fast, image
Inorganization Structural superposition, anatomy relationship are clear and definite, image is clear, density resolution is high, hurtless measure is with painful
Etc. advantage (J.Nucl.Med.2013,54 (11), 1938-1945, JACC-Cardiovasc.Imag.2013,6
(12),1229-1238,Clin.Oral Implant.Res.2013,24(7),746-749).For enhanced CT
Image effect, the most usually needs to use contrast agent.The contrast agent used in CT image has following several
Type: 1. injection contrast agent in vein or arteries；2. cholegraphic agent；3. gastrointestinal tract is administered orally
Contrast agent；4. canalis spinalis and ventricles of the brain CT radiography contrast agent；5. liver spleen specific contrast agent；6. lymphsystem
Contrast agent.The present invention finds under study for action, and zirconium dioxide material self has good CT enhanced sensitivity performance,
Can be as good CT contrast agent, and the longer internal blood circulation of this material, excellent internal peace
Quan Xing, tumor tissue specificity, cost be relatively low and highly sensitive feature, is expected to become structure new CT
The preferred material of contrast agent.
On traditional clinical, the diagnosis of disease and treatment are two self-contained process, and diagnosis and medicine for treatment are also
Two kinds of independent medicines.Cancer patient is for accepting corresponding instrument diagnosis, contrast agent to be used, and controls
Other drug to be used during treatment.Such twice medical procedure is longer for interval time, easily affects adversely and most preferably controls
Treatment opportunity, also can increase misery and the risk of patient.Further, since medicine for diagnosis and medicine for treatment thing
Generally all patient is had certain side effect, be divided into twice medication can increase the unnecessary misery of patient and wind
Danger.Therefore, can diagnostic agent and medicine for treatment unite two into one, always a disaster of biological medicine circle
Topic.The hollow zirconium dioxide kernel appendix with CT enhancing performance is had microwave enhanced sensitivity performance by the present invention
Ionic liquid, obtains a kind of multi-functional nanometer material, can apply simultaneously to tumor microwave heat treatment field and
CT imaging field, thus realize the diagnosis and treatment integration of tumor.Current multifunctional nano material of the present invention
Material have not been reported.
Summary of the invention
First technical problem that the invention solves the problems that is to provide one and has tumor microwave heat treatment and CT imaging
The multi-functional hollow Ions in nanocrystalline zirconia of function, this hollow nano-material has good bio-compatible
Property, have no side effect, be used directly in animal body, be applied to tumor microwave heat treatment and CT
Imaging technique, has good clinic diagnosis using value.
Second technical problem that the invention solves the problems that is to provide for tumor microwave heat treatment and CT imaging technique
The preparation method of multi-functional hollow Ions in nanocrystalline zirconia, hollow nano-material shape prepared by this method
Looks are good, narrow diameter distribution, shell thickness, size tunable.
The 3rd technical problem that the invention solves the problems that is to provide Multifunctional air heart Ions in nanocrystalline zirconia and exists
Application in tumor microwave heat treatment.
The 4th technical problem that the invention solves the problems that is to provide Multifunctional air heart Ions in nanocrystalline zirconia and exists
Application in CT imaging technique.
For solving above-mentioned first technical problem, the present invention uses following technical proposals:
It is a kind of for tumor microwave heat treatment and the multi-functional hollow Ions in nanocrystalline zirconia of CT imaging technique,
Described hollow nano-material a diameter of 50～1000nm, the shell thickness of described hollow nano-material is
10～500nm；Described hollow nano-material kernel appendix has the ionic liquid of microwave enhanced sensitivity performance.
Preferably, described hollow nano-material a diameter of 250～450nm, the shell of described hollow nano-material
Layer thickness is 50～120nm.
Described hollow nano-material particle diameter narrow distribution, shell thickness and size is controlled, in water with second
Alcohol is respectively provided with good dispersibility；Described hollow nano-material, its Shell Materials zirconium dioxide has CT
Strengthen performance, can be applicable to CT image-forming contrast medium in organism.
Preferably, described ionic liquid is selected from 1-butyl-3-methyl imidazolium tetrafluoroborate, 1-butyl-3-first
Base limidazolium hexafluorophosphate, 1-butyl-3-Methylimidazole. L lactate, chlorination 1-cyanogen methyl-3-Methylimidazole.,
One or more in chlorination 1-carboxymethyl-3-Methylimidazole. or chlorination 1-amine propyl group-3-Methylimidazole..
For solving above-mentioned second technical problem, the present invention uses following technical proposals:
System for tumor microwave heat treatment Yu the multi-functional hollow Ions in nanocrystalline zirconia of CT imaging technique
Preparation Method, comprises the steps:
1) being scattered in dehydrated alcohol by ionic liquid, volume fraction is 1～10%, ultrasonic or dispersed with stirring
Uniformly；
2) to step 1) the ionic liquid dispersion liquid that obtains adds hollow Ions in nanocrystalline zirconia, matter
Amount volume fraction is 1～10mg mL-1, supersound process 30～60 minutes under vacuum conditions；
3) by step 2) appendix that obtains has the hollow Ions in nanocrystalline zirconia of ionic liquid to use nothing successively
Water-ethanol and deionized water wash, obtain multi-functional hollow Ions in nanocrystalline zirconia.
Preferably, step 1) described in solvent selected from deionized water, dehydrated alcohol, acetonitrile, DMSO,
One or more in 1,4-dioxane, normal hexane, hexamethylene or isopropanol.
Preferably, step 1) described in ionic liquid selected from 1-butyl-3-methyl imidazolium tetrafluoroborate,
1-butyl-3-Methylimidazole. hexafluorophosphate, 1-butyl-3-Methylimidazole. L lactate, chlorination 1-cyanogen methyl
One in-3-Methylimidazole., chlorination 1-carboxymethyl-3-Methylimidazole. or chlorination 1-amine propyl group-3-Methylimidazole.
Or it is several.
3rd technical problem to be solved by this invention is to provide Multifunctional air heart Ions in nanocrystalline zirconia
Application in tumor microwave heat treatment technology, has the multi-functional hollow zirconium dioxide of ionic liquid to receive by appendix
Rice material is dispersed in normal saline, and compound concentration scope is 0～40mg mL-1Dispersion liquid, put respectively
In external microwave heating device, microwave irradiation processes；Or appendix is had the hollow titanium dioxide of ionic liquid
Zirconium nano material is dispersed in normal saline, and compound concentration is 1～10mg mL-1Dispersion liquid, pass through tail
Intravenous injection is in the Mice Body of inoculated tumour, and microwave irradiation knub position, tumor by local temperature can be fast
Speed reaches more than 43 DEG C, and this temperature be enough to kill tumor cell.
4th technical problem to be solved by this invention is to provide Multifunctional air heart Ions in nanocrystalline zirconia
Application in CT imaging technique, by 0～40mg mL-1The hollow zirconium dioxide nanometer material of variable concentrations
Material carries out external CT imaging, and CT value has concentration dependent.
Preferably, being dispersed in normal saline by hollow Ions in nanocrystalline zirconia, compound concentration is 1～10
mg mL-1Dispersion liquid, by tail vein injection in the Mice Body of inoculated tumour, different time sections is carried out
Internal CT imaging.
Beneficial effects of the present invention is as follows:
1, the present invention and prior art is dramatically different, by the hollow dioxy of multifunction in the present invention
Change zirconium nano material and apply simultaneously to tumor microwave heat treatment and CT technical field of imaging, and achieve good
Diagnostic and therapeutic effect, substantially increases diagnoses and treatment efficiency, has good clinical value.
2, of the present invention for tumor microwave heat treatment and the multi-functional hollow titanium dioxide of CT imaging technique
Zirconium nano material, its kernel appendix has the ionic liquid with microwave enhanced sensitivity performance, due at room temperature from
Sub-liquid is made up of the ion of positively charged and negative electricity, and its cationic has good conductivity and polarizability,
Making them that function of ion polarization can occur under microwave radiation, the frequent change in microwave direction can cause ion
Liquid polarized direction changes the most therewith, and interionic collides with each other, frictional heat, and microwave energy is direct
It is converted into heat energy, and then the form raised with temperature shows, and has excellent microwave effect of enhanced sensitivity.
3, of the present invention for tumor microwave heat treatment and the multi-functional hollow titanium dioxide of CT imaging technique
Zirconium nano material, its shell is zirconium dioxide, has preferable CT and strengthens performance, can be as good
CT contrast agent.
4, of the present invention for tumor microwave heat treatment and the multi-functional hollow titanium dioxide of CT imaging technique
Zirconium nano material, by ionic liquid appendix after hollow zirconium dioxide kernel, fully remains ion
The microwave enhanced sensitivity character of liquid and the CT imaging performance of zirconium dioxide, obtained a kind of for tumor microwave
Thermotherapy and the multi-functional hollow Ions in nanocrystalline zirconia of CT imaging technique.
Accompanying drawing explanation
Below in conjunction with the accompanying drawings the detailed description of the invention of the present invention is described in further detail.
It is many for tumor microwave heat treatment and CT imaging technique that Fig. 1 illustrates obtained by the embodiment of the present invention 1
The transmission electron microscope photo of the hollow Ions in nanocrystalline zirconia of function；
It is many for tumor microwave heat treatment and CT imaging technique that Fig. 2 illustrates obtained by the embodiment of the present invention 1
The transmission electron microscope photo of the shell of the hollow Ions in nanocrystalline zirconia of function；
It is many for tumor microwave heat treatment and CT imaging technique that Fig. 3 illustrates obtained by the embodiment of the present invention 1
The electron scanning micrograph of the hollow Ions in nanocrystalline zirconia of function；
It is many for tumor microwave heat treatment and CT imaging technique that Fig. 4 illustrates obtained by the embodiment of the present invention 1
The grain size distribution sheet of the hollow Ions in nanocrystalline zirconia of function；
It is many for tumor microwave heat treatment and CT imaging technique that Fig. 5 illustrates obtained by the embodiment of the present invention 1
The microwave temperature rise effect of the hollow Ions in nanocrystalline zirconia of function.
Detailed description of the invention
In order to be illustrated more clearly that the present invention, below in conjunction with preferred embodiments and drawings, the present invention is done further
Explanation.Parts similar in accompanying drawing are indicated with identical reference.Those skilled in the art should
Understand, below specifically described content be illustrative and be not restrictive, the present invention should not limited with this
Protection domain.
Embodiment 1
(1) 1-butyl-3-methyl imidazolium tetrafluoroborate being scattered in deionized water, volume fraction is
1%, ultrasonic or dispersed with stirring is uniform；
(2) to step 1) the 1-butyl-3-methyl imidazolium tetrafluoroborate dispersion liquid that obtains adds hollow
Ions in nanocrystalline zirconia, mass body fraction is 1mg mL-1, supersound process about 30 under vacuum conditions
Minute；
(3) by step 2) appendix that obtains has the hollow dioxy of 1-butyl-3-methyl imidazolium tetrafluoroborate
Change zirconium nano material successively with dehydrated alcohol and deionized water wash；
(4) step 3) the hollow Ions in nanocrystalline zirconia that obtains has CT simultaneously and strengthens and increase with microwave
Quick performance, is a kind of multi-functional hollow nano-material.
From Fig. 1-4 can with clear view to, the hollow Ions in nanocrystalline zirconia of gained is uniformly distributed, grain
Footpath narrow distribution, a diameter of 350nm, shell thickness is 50nm, and obvious with transmission image by scanning
Can be seen that resulting materials is hollow-core construction.
The multi-functional hollow Ions in nanocrystalline zirconia prepared by the present embodiment is used for tumor microwave heat treatment
Technology, the intensification experiment of its external and internal microwave is as follows with tumor thermotherapy effect:
Appendix is had the multi-functional hollow Ions in nanocrystalline zirconia of 1-butyl-3-methyl imidazolium tetrafluoroborate
Being dispersed in normal saline, configuration concentration is 40mg mL-1Dispersion liquid, be placed in external microwave heat up set
In Bei, microwave irradiation process, the isopyknic normal saline of matched group, intensification result as it is shown in figure 5,
Respond well.The experiment that heats up in animal body is as follows: appendix has 1-butyl-3-methyl imidazolium tetrafluoroborate
Multi-functional hollow Ions in nanocrystalline zirconia be dispersed in normal saline, tail vein injection in inoculation H22
In the ICR Mice Body of tumor, injection dosage is 10～40mg kg-1, after 12 hours, microwave irradiation processes,
Knub position temperature can be rapidly reached more than 43 DEG C, and this temperature be enough to kill tumor cell；Two weeks is left
Right knub position returns to one's perfect health, and skin recovers normal completely.
The multi-functional hollow Ions in nanocrystalline zirconia prepared by the present embodiment is used for CT imaging technique,
It is external and in-vivo imaging effect is as follows:
Appendix is had the multi-functional hollow Ions in nanocrystalline zirconia of 1-butyl-3-methyl imidazolium tetrafluoroborate
Being dispersed in normal saline, be formulated as different gradient concentration dispersion liquid, concentration range is 0～40mg mL-1,
Carrying out external CT imaging respectively, CT value has concentration dependent, has good imaging effect.Animal
Internal CT imaging experiment is as follows: appendix has the Multifunctional air of 1-butyl-3-methyl imidazolium tetrafluoroborate
Heart Ions in nanocrystalline zirconia is dispersed in normal saline, and tail vein injection is in the ICR of inoculation H22 tumor
In Mice Body, injection dosage is 10～40mg kg-1, different time sections carries out internal CT imaging, tumor
Position has obvious CT enhancement effect, and CT strengthens can reach 8～10 times, has good diagnosis effect
Really.
Embodiment 2
(1) being scattered in deionized water by 1-butyl-3-Methylimidazole. hexafluorophosphate, volume fraction is
10%, ultrasonic or dispersed with stirring is uniform；
(2) to step 1) the 1-butyl-3-Methylimidazole. hexafluorophosphate dispersion liquid that obtains adds hollow
Ions in nanocrystalline zirconia, mass body fraction is 10mg mL-1, supersound process is about under vacuum conditions
60 minutes；
(3) by step 2) appendix that obtains has the hollow dioxy of 1-butyl-3-Methylimidazole. hexafluorophosphate
Change zirconium nano material successively with dehydrated alcohol and deionized water wash；
(4) step 3) the hollow Ions in nanocrystalline zirconia that obtains has CT simultaneously and strengthens and increase with microwave
Quick performance, is a kind of multi-functional hollow nano-material.
The multi-functional hollow Ions in nanocrystalline zirconia prepared by the present embodiment is used for tumor microwave heat treatment
Technology, the intensification experiment of its external and internal microwave is as follows with tumor thermotherapy effect:
Appendix is had the multi-functional hollow Ions in nanocrystalline zirconia of 1-butyl-3-Methylimidazole. hexafluorophosphate
Being dispersed in normal saline, configuration concentration is 0～40mg mL-1Dispersion liquid, be placed in external microwave heat up
In equipment, microwave irradiation processes, and the isopyknic normal saline of matched group, temperature rise effect is good.Animal
The internal experiment that heats up is as follows: appendix has multi-functional hollow the two of 1-butyl-3-Methylimidazole. hexafluorophosphate
Nanometer zirconium oxide is dispersed in normal saline, and tail vein injection is in the ICR mice of inoculation H22 tumor
Internal, injection dosage is 10～40mg kg-1, after 12 hours, microwave irradiation processes, knub position temperature
Can be rapidly reached more than 43 DEG C, this temperature be enough to kill tumor cell；Two weeks left and right knub position is complete
Full rehabilitation, skin recovers normal completely.
The multi-functional hollow Ions in nanocrystalline zirconia prepared by the present embodiment is used for CT imaging technique,
It is external and in-vivo imaging effect is as follows:
Appendix is had the multi-functional hollow Ions in nanocrystalline zirconia of 1-butyl-3-Methylimidazole. hexafluorophosphate
Being dispersed in normal saline, be formulated as different gradient concentration dispersion liquid, concentration range is 0～40mg mL-1,
Carrying out external CT imaging respectively, CT value has concentration dependent, has good imaging effect.Animal
Internal CT imaging experiment is as follows: appendix has the Multifunctional air of 1-butyl-3-Methylimidazole. hexafluorophosphate
Heart Ions in nanocrystalline zirconia is dispersed in normal saline, and tail vein injection is in the ICR of inoculation H22 tumor
In Mice Body, injection dosage is 10～40mg kg-1, different time sections carries out internal CT imaging, tumor
Position has obvious CT enhancement effect, and CT strengthens can reach 8～10 times, has good diagnosis effect
Really.
Embodiment 3
(1) being scattered in deionized water by 1-butyl-3-Methylimidazole. L lactate, volume fraction is 3%,
Ultrasonic or dispersed with stirring is uniform；
(2) to step 1) the 1-butyl-3-Methylimidazole. L lactate dispersion liquid that obtains adds hollow two
Nanometer zirconium oxide, mass body fraction is 2mg mL-1, supersound process about 40 points under vacuum conditions
Clock；
(3) by step 2) appendix that obtains has the 1-butyl Lactated hollow titanium dioxide of-3-Methylimidazole. L
Zirconium nano material is successively with dehydrated alcohol and deionized water wash；
(4) step 3) the hollow Ions in nanocrystalline zirconia that obtains has CT simultaneously and strengthens and increase with microwave
Quick performance, is a kind of multi-functional hollow nano-material.
The multi-functional hollow Ions in nanocrystalline zirconia prepared by the present embodiment is used for tumor microwave heat treatment
Technology, the intensification experiment of its external and internal microwave is as follows with tumor thermotherapy effect:
Appendix have the 1-Lactated multi-functional hollow Ions in nanocrystalline zirconia of butyl-3-Methylimidazole. L divide
Being dispersed in normal saline, configuration concentration is 0～40mg mL-1Dispersion liquid, be placed in external microwave heat up set
In Bei, microwave irradiation processes, and the isopyknic normal saline of matched group, temperature rise effect is good.Animal body
The interior experiment that heats up is as follows: appendix has the 1-Lactated multi-functional hollow titanium dioxide of butyl-3-Methylimidazole. L
Zirconium nano material is dispersed in normal saline, tail vein injection in inoculation H22 tumor ICR Mice Body in,
Injection dosage is 10～40mg kg-1, after 12 hours, microwave irradiation processes, and knub position temperature can be fast
Speed reaches more than 43 DEG C, and this temperature be enough to kill tumor cell；Two weeks left and right knub position returns to one's perfect health,
Skin recovers normal completely.
The multi-functional hollow Ions in nanocrystalline zirconia prepared by the present embodiment is used for CT imaging technique,
It is external and in-vivo imaging effect is as follows:
Appendix have the 1-Lactated multi-functional hollow Ions in nanocrystalline zirconia of butyl-3-Methylimidazole. L divide
Being dispersed in normal saline, be formulated as different gradient concentration dispersion liquid, concentration range is 0～40mg mL-1,
Carrying out external CT imaging respectively, CT value has concentration dependent, has good imaging effect.Animal
Internal CT imaging experiment is as follows: appendix has 1-butyl-3-Methylimidazole. L Lactated multi-functional hollow
Ions in nanocrystalline zirconia is dispersed in normal saline, and tail vein injection is little in the ICR of inoculation H22 tumor
In Mus body, injection dosage is 10～40mg kg-1, different time sections carries out internal CT imaging, tumor position
Putting and have obvious CT enhancement effect, CT strengthens can reach 8～10 times, has good diagnosis effect.
Embodiment 4
(1) being scattered in deionized water by chlorination 1-cyanogen methyl-3-Methylimidazole., volume fraction is 6%,
Ultrasonic or dispersed with stirring is uniform；
(2) to step 1) the chlorination 1-cyanogen methyl-3-Methylimidazole. dispersion liquid that obtains adds hollow dioxy
Changing zirconium nano material, mass body fraction is 5mg mL-1, supersound process about 45 minutes under vacuum conditions；
(3) by step 2) appendix that obtains has the hollow zirconium dioxide of chlorination 1-cyanogen methyl-3-Methylimidazole.
Nano material is successively with dehydrated alcohol and deionized water wash；
(4) step 3) the hollow Ions in nanocrystalline zirconia that obtains has CT simultaneously and strengthens and increase with microwave
Quick performance, is a kind of multi-functional hollow nano-material.
The multi-functional hollow Ions in nanocrystalline zirconia prepared by the present embodiment is used for tumor microwave heat treatment
Technology, the intensification experiment of its external and internal microwave is as follows with tumor thermotherapy effect:
The multi-functional hollow Ions in nanocrystalline zirconia that appendix has chlorination 1-cyanogen methyl-3-Methylimidazole. disperses
In normal saline, configuration concentration is 0～40mg mL-1Dispersion liquid, be placed in external microwave heating device
In, microwave irradiation processes, and the isopyknic normal saline of matched group, temperature rise effect is good.In animal body
The experiment that heats up is as follows: appendix has the multi-functional hollow zirconium dioxide of chlorination 1-cyanogen methyl-3-Methylimidazole. receive
Rice material is dispersed in normal saline, and tail vein injection, in the ICR Mice Body of inoculation H22 tumor, is noted
Penetrating dosage is 10～40mg kg-1, after 12 hours, microwave irradiation processes, and knub position temperature can be rapid
Reaching more than 43 DEG C, this temperature be enough to kill tumor cell；Two weeks left and right knub position returns to one's perfect health,
Skin recovers normal completely.
The multi-functional hollow Ions in nanocrystalline zirconia prepared by the present embodiment is used for CT imaging technique,
It is external and in-vivo imaging effect is as follows:
The multi-functional hollow Ions in nanocrystalline zirconia that appendix has chlorination 1-cyanogen methyl-3-Methylimidazole. disperses
In normal saline, being formulated as different gradient concentration dispersion liquid, concentration range is 0～40mg mL-1, point
Not carrying out external CT imaging, CT value has concentration dependent, has good imaging effect.Animal body
Interior CT imaging experiment is as follows: appendix has the multi-functional hollow dioxy of chlorination 1-cyanogen methyl-3-Methylimidazole.
Changing zirconium nano material to be dispersed in normal saline, tail vein injection is in the ICR Mice Body of inoculation H22 tumor
In, injection dosage is 10～40mg kg-1, different time sections carries out internal CT imaging, and knub position has
Having obvious CT enhancement effect, CT strengthens can reach 8～10 times, has good diagnosis effect.
Embodiment 5
(1) being scattered in deionized water by chlorination 1-carboxymethyl-3-Methylimidazole., volume fraction is 8%,
Ultrasonic or dispersed with stirring is uniform；
(2) to step 1) the chlorination 1-carboxymethyl-3-Methylimidazole. dispersion liquid that obtains adds hollow dioxy
Changing zirconium nano material, mass body fraction is 7mg mL-1, supersound process about 30 points under vacuum conditions
Clock；
(3) by step 2) appendix that obtains has the hollow zirconium dioxide of chlorination 1-carboxymethyl-3-Methylimidazole.
Nano material is successively with dehydrated alcohol and deionized water wash；
(4) step 3) the hollow Ions in nanocrystalline zirconia that obtains has CT simultaneously and strengthens and increase with microwave
Quick performance, is a kind of multi-functional hollow nano-material.
The multi-functional hollow Ions in nanocrystalline zirconia prepared by the present embodiment is used for tumor microwave heat treatment
Technology, the intensification experiment of its external and internal microwave is as follows with tumor thermotherapy effect:
The multi-functional hollow Ions in nanocrystalline zirconia that appendix has chlorination 1-carboxymethyl-3-Methylimidazole. disperses
In normal saline, configuration concentration is 0～40mg mL-1Dispersion liquid, be placed in external microwave heating device
In, microwave irradiation processes, and the isopyknic normal saline of matched group, temperature rise effect is good.In animal body
The experiment that heats up is as follows: appendix has the multi-functional hollow zirconium dioxide of chlorination 1-carboxymethyl-3-Methylimidazole. receive
Rice material is dispersed in normal saline, and tail vein injection, in the ICR Mice Body of inoculation H22 tumor, is noted
Penetrating dosage is 10～40mg kg-1, after 12 hours, microwave irradiation processes, and knub position temperature can be rapid
Reaching more than 43 DEG C, this temperature be enough to kill tumor cell；Two weeks left and right knub position returns to one's perfect health,
Skin recovers normal completely.
The multi-functional hollow Ions in nanocrystalline zirconia prepared by the present embodiment is used for CT imaging technique,
It is external and in-vivo imaging effect is as follows:
The multi-functional hollow Ions in nanocrystalline zirconia that appendix has chlorination 1-carboxymethyl-3-Methylimidazole. disperses
In normal saline, being formulated as different gradient concentration dispersion liquid, concentration range is 0～40mg mL-1, point
Not carrying out external CT imaging, CT value has concentration dependent, has good imaging effect.Animal body
Interior CT imaging experiment is as follows: appendix has the multi-functional hollow dioxy of chlorination 1-carboxymethyl-3-Methylimidazole.
Changing zirconium nano material to be dispersed in normal saline, tail vein injection is in the ICR Mice Body of inoculation H22 tumor
In, injection dosage is 10～40mg kg-1, different time sections carries out internal CT imaging, and knub position has
Having obvious CT enhancement effect, CT strengthens can reach 8～10 times, has good diagnosis effect.
Embodiment 6
(1) being scattered in deionized water by chlorination 1-amine propyl group-3-Methylimidazole., volume fraction is 5%,
Ultrasonic or dispersed with stirring is uniform；
(2) to step 1) the chlorination 1-amine propyl group-3-Methylimidazole. dispersion liquid that obtains adds hollow dioxy
Changing zirconium nano material, mass body fraction is 5mg mL-1, supersound process about 60 minutes under vacuum conditions；
(3) by step 2) appendix that obtains has the hollow zirconium dioxide of chlorination 1-amine propyl group-3-Methylimidazole.
Nano material is successively with dehydrated alcohol and deionized water wash；
(4) step 3) the hollow Ions in nanocrystalline zirconia that obtains has CT simultaneously and strengthens and increase with microwave
Quick performance, is a kind of multi-functional hollow nano-material.
The multi-functional hollow Ions in nanocrystalline zirconia prepared by the present embodiment is used for tumor microwave heat treatment
Technology, the intensification experiment of its external and internal microwave is as follows with tumor thermotherapy effect:
The multi-functional hollow Ions in nanocrystalline zirconia that appendix has chlorination 1-amine propyl group-3-Methylimidazole. disperses
In normal saline, configuration concentration is 0～40mg mL-1Dispersion liquid, be placed in external microwave heating device
In, microwave irradiation processes, and the isopyknic normal saline of matched group, temperature rise effect is good.In animal body
The experiment that heats up is as follows: appendix has the multi-functional hollow zirconium dioxide of chlorination 1-amine propyl group-3-Methylimidazole. receive
Rice material is dispersed in normal saline, and tail vein injection, in the ICR Mice Body of inoculation H22 tumor, is noted
Penetrating dosage is 10～40mg kg-1, after 12 hours, microwave irradiation processes, and knub position temperature can be rapid
Reaching more than 43 DEG C, this temperature be enough to kill tumor cell；Two weeks left and right knub position returns to one's perfect health,
Skin recovers normal completely.
The multi-functional hollow Ions in nanocrystalline zirconia prepared by the present embodiment is used for CT imaging technique,
It is external and in-vivo imaging effect is as follows:
The multi-functional hollow Ions in nanocrystalline zirconia that appendix has chlorination 1-amine propyl group-3-Methylimidazole. disperses
In normal saline, being formulated as different gradient concentration dispersion liquid, concentration range is 0～40mg mL-1, point
Not carrying out external CT imaging, CT value has concentration dependent, has good imaging effect.Animal body
Interior CT imaging experiment is as follows: appendix has the multi-functional hollow dioxy of chlorination 1-amine propyl group-3-Methylimidazole.
Changing zirconium nano material to be dispersed in normal saline, tail vein injection is in the ICR Mice Body of inoculation H22 tumor
In, injection dosage is 10～40mg kg-1, different time sections carries out internal CT imaging, and knub position has
Having obvious CT enhancement effect, CT strengthens can reach 8～10 times, has good diagnosis effect.
Embodiment 7～13
With embodiment 1, it the difference is that only, the solvent deionized water used by step (1) is used respectively
Dehydrated alcohol, acetonitrile, DMSO, Isosorbide-5-Nitrae-dioxane, normal hexane, hexamethylene or isopropanol replace, knot
The most similar.
Obviously, the above embodiment of the present invention is only for clearly demonstrating example of the present invention, and not
It is the restriction to embodiments of the present invention, for those of ordinary skill in the field, states upper
Can also make other changes in different forms on the basis of bright, here cannot be to all of embodiment party
Formula gives exhaustive, every belongs to obvious change that technical scheme extended out or variation still
It is in the row of protection scope of the present invention.
Claims (5)
1. one kind is used for tumor microwave heat treatment and the multi-functional hollow zirconium dioxide nanometer material of CT imaging technique
Material, it is characterised in that: described hollow nano-material a diameter of 50～1000nm, shell thickness is 10～500
nm；The inside appendix of described hollow nano-material has the ionic liquid of microwave enhanced sensitivity performance, Qi Zhongsuo
State ionic liquid selected from 1-butyl-3-methyl imidazolium tetrafluoroborate, 1-butyl-3-Methylimidazole. hexafluorophosphoric acid
Salt, 1-butyl-3-Methylimidazole. L lactate, chlorination 1-cyanogen methyl-3-Methylimidazole., chlorination 1-carboxymethyl
One or more in-3-Methylimidazole. or chlorination 1-amine propyl group-3-Methylimidazole..
Multi-functional hollow Ions in nanocrystalline zirconia the most according to claim 1, it is characterised in that:
Preferably, described hollow nano-material a diameter of 250～450nm, the shell of described hollow nano-material is thick
Degree is 50～120nm.
Many merits for tumor microwave heat treatment Yu CT imaging technique the most according to claim 1 and 2
The preparation method of the hollow Ions in nanocrystalline zirconia of energy, it is characterised in that comprise the steps:
1) being scattered in solvent by ionic liquid, volume fraction is 1～10%, ultrasonic or dispersed with stirring is uniform；
2) to step 1) the ionic liquid dispersion liquid that obtains adds hollow Ions in nanocrystalline zirconia, matter
Amount volume fraction is 1～10mg mL-1, supersound process 30～60 minutes under vacuum conditions；
3) by step 2) appendix that obtains has the hollow Ions in nanocrystalline zirconia of ionic liquid to use nothing successively
Water-ethanol and deionized water wash, obtain multi-functional hollow Ions in nanocrystalline zirconia.
Multifunctional air for tumor microwave heat treatment Yu CT imaging technique the most according to claim 3
The preparation method of heart Ions in nanocrystalline zirconia, it is characterised in that: step 1) described in solvent selected from go from
In sub-water, dehydrated alcohol, acetonitrile, DMSO, 1,4-dioxane, normal hexane, hexamethylene or isopropanol
One.
Multifunctional air for tumor microwave heat treatment Yu CT imaging technique the most according to claim 3
The preparation method of heart Ions in nanocrystalline zirconia, it is characterised in that: step 1) described in ionic liquid be selected from
1-butyl-3-methyl imidazolium tetrafluoroborate, 1-butyl-3-Methylimidazole. hexafluorophosphate, 1-butyl-3-first
Base imidazoles L lactate, chlorination 1-cyanogen methyl-3-Methylimidazole., chlorination 1-carboxymethyl-3-Methylimidazole., chlorine
Change one or more in 1-amine propyl group-3-Methylimidazole..
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410453049.2A CN104208685B (en) | 2014-09-05 | 2014-09-05 | A kind of hollow Ions in nanocrystalline zirconia with tumor microwave heat treatment and CT imaging function and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410453049.2A CN104208685B (en) | 2014-09-05 | 2014-09-05 | A kind of hollow Ions in nanocrystalline zirconia with tumor microwave heat treatment and CT imaging function and its preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104208685A CN104208685A (en) | 2014-12-17 |
| CN104208685B true CN104208685B (en) | 2016-08-10 |
Family
ID=52090857
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410453049.2A Active CN104208685B (en) | 2014-09-05 | 2014-09-05 | A kind of hollow Ions in nanocrystalline zirconia with tumor microwave heat treatment and CT imaging function and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104208685B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107812191B (en) * | 2015-02-12 | 2020-07-31 | 中国医科大学附属第一医院 | A dispersion for chemotherapy, microwave thermotherapy and CT imaging |
| CN113925970B (en) * | 2021-11-25 | 2023-01-03 | 中国科学院过程工程研究所 | Application of tumor photothermal preparation |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110034916A1 (en) * | 2008-04-09 | 2011-02-10 | Alexis Te | Nanoparticle-mediated microwave treatment methods |
| CN102327625A (en) * | 2011-08-19 | 2012-01-25 | 中国科学院宁波材料技术与工程研究所 | Water-soluble nano composite material and preparation method and use thereof |
-
2014
- 2014-09-05 CN CN201410453049.2A patent/CN104208685B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110034916A1 (en) * | 2008-04-09 | 2011-02-10 | Alexis Te | Nanoparticle-mediated microwave treatment methods |
| CN102327625A (en) * | 2011-08-19 | 2012-01-25 | 中国科学院宁波材料技术与工程研究所 | Water-soluble nano composite material and preparation method and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104208685A (en) | 2014-12-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wu et al. | Deep-tissue photothermal therapy using laser illumination at NIR-IIa window | |
| Dai et al. | Two-dimensional tantalum carbide (MXenes) composite nanosheets for multiple imaging-guided photothermal tumor ablation | |
| Zhang et al. | A multifunctional theranostic nanoagent for dual-mode image-guided HIFU/chemo-synergistic cancer therapy | |
| CN104474559B (en) | Hollow mesoporous prussian blue nano photo-thermal diagnosis and treatment agent with ultrasound contrast function and preparation method of hollow mesoporous prussian blue nano photo-thermal diagnosis and treatment agent | |
| Wang et al. | A self‐assembled biocompatible nanoplatform for multimodal MR/fluorescence imaging assisted photothermal therapy and prognosis analysis | |
| Chiang et al. | Biofunctional core-shell polypyrrole–polyethylenimine nanocomplex for a locally sustained photothermal with reactive oxygen species enhanced therapeutic effect against lung cancer | |
| CN108671231B (en) | Multifunctional nano-carrier for tumor photothermal synergistic treatment and ultrasonic imaging and preparation method thereof | |
| CN104208685B (en) | A kind of hollow Ions in nanocrystalline zirconia with tumor microwave heat treatment and CT imaging function and its preparation method and application | |
| CN104436193A (en) | Preparation method of folic acid coupled gold nano-rod/polypyrrole/ferroferric oxide multifunctional composite nano diagnosis and treatment agent | |
| CN104888216B (en) | Delay the zirconium dioxide composite nano materials and preparation method and application of controlled release and CT imaging functions with microwave enhanced sensitivity, chemotherapeutics | |
| Zhao et al. | Recent progress of nanogenerators acting as self‐powered drug delivery devices | |
| CN104069494B (en) | A kind of sodium alginate micro gel capsule for tumor microwave heat treatment technology and its preparation method and application | |
| CN206138577U (en) | Targetable drug delivery device of antitumor nano particles medicine | |
| CN104225631B (en) | A kind of have nuclear magnetic resonance microcapsule with micro-wave therapeutic tumor function and its preparation method and application | |
| CN104117074B (en) | A kind for the treatment of diagnostic preparation based on polypyrrole complex and preparation method thereof | |
| CN107837404B (en) | A kind of nanoparticle diagnosing tumor treatment combination preparation and its preparation method and application | |
| CN103432585A (en) | Targeted marking system for efficiently mediating folate receptor-alpha subtype | |
| CN103341057B (en) | Chinese patent medicine pill for treating calculus, nephritis and cholecystitis | |
| CN105169420B (en) | A kind of New-type radio-frequency diagnosis and treatment agent and preparation method thereof | |
| CN1562225A (en) | Medication for curing hematuria caused by multiform kidney disease and it prepn. process | |
| CN102028794A (en) | Gynecological disease resisting gel for treating gynecological disease and preparation method thereof | |
| Silva Pedraza et al. | Development of Ferroelectric P (VDF-TrFE) Microparticles for Ultrasound-Driven Cancer Cell Killing | |
| CN107496416A (en) | It is a kind of to be used to treat EGCG spices medicines of Parkinson's and preparation method thereof | |
| CN106729125A (en) | It is a kind of to treat composition of acne and application thereof | |
| Roopashree et al. | Advent of nanomaterial in modern health science and ayurveda |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |