CN108187048A - A kind of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent and preparation method thereof - Google Patents
A kind of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent and preparation method thereof Download PDFInfo
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- 238000003745 diagnosis Methods 0.000 title claims abstract description 61
- 239000003153 chemical reaction reagent Substances 0.000 title claims abstract description 53
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 239000003446 ligand Substances 0.000 claims abstract description 47
- 229910001428 transition metal ion Inorganic materials 0.000 claims abstract description 37
- 239000002243 precursor Substances 0.000 claims abstract description 35
- 229910052723 transition metal Inorganic materials 0.000 claims abstract description 29
- 150000003624 transition metals Chemical class 0.000 claims abstract description 29
- 238000010521 absorption reaction Methods 0.000 claims abstract description 18
- 230000005291 magnetic effect Effects 0.000 claims abstract description 13
- 230000007704 transition Effects 0.000 claims abstract description 8
- 230000008859 change Effects 0.000 claims abstract description 7
- 230000003993 interaction Effects 0.000 claims abstract description 6
- 230000005408 paramagnetism Effects 0.000 claims abstract description 6
- 239000000243 solution Substances 0.000 claims description 117
- 230000005298 paramagnetic effect Effects 0.000 claims description 52
- 229910021645 metal ion Inorganic materials 0.000 claims description 27
- 206010028980 Neoplasm Diseases 0.000 claims description 22
- 239000011259 mixed solution Substances 0.000 claims description 16
- 239000002086 nanomaterial Substances 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 239000005864 Sulphur Substances 0.000 claims description 12
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical group OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 claims description 12
- 125000003916 ethylene diamine group Chemical group 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 11
- VRWKTAYJTKRVCU-UHFFFAOYSA-N iron(6+);hexacyanide Chemical compound [Fe+6].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] VRWKTAYJTKRVCU-UHFFFAOYSA-N 0.000 claims description 11
- 239000000463 material Substances 0.000 claims description 8
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 claims description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 6
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 claims description 6
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 6
- 229910002651 NO3 Inorganic materials 0.000 claims description 6
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 6
- 150000004820 halides Chemical class 0.000 claims description 6
- 150000003891 oxalate salts Chemical class 0.000 claims description 6
- 239000011365 complex material Substances 0.000 claims description 4
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- 150000001455 metallic ions Chemical class 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 2
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 claims 2
- 238000007626 photothermal therapy Methods 0.000 abstract description 9
- 238000002595 magnetic resonance imaging Methods 0.000 abstract description 7
- 239000002872 contrast media Substances 0.000 abstract description 2
- 150000004696 coordination complex Chemical class 0.000 abstract 1
- 230000001052 transient effect Effects 0.000 abstract 1
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 43
- 239000002105 nanoparticle Substances 0.000 description 33
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- 229940074391 gallic acid Drugs 0.000 description 21
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- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 12
- 229940032296 ferric chloride Drugs 0.000 description 12
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 12
- 239000008367 deionised water Substances 0.000 description 10
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- CTENFNNZBMHDDG-UHFFFAOYSA-N Dopamine hydrochloride Chemical compound Cl.NCCC1=CC=C(O)C(O)=C1 CTENFNNZBMHDDG-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- MQRWBMAEBQOWAF-UHFFFAOYSA-N acetic acid;nickel Chemical compound [Ni].CC(O)=O.CC(O)=O MQRWBMAEBQOWAF-UHFFFAOYSA-N 0.000 description 3
- 229960001149 dopamine hydrochloride Drugs 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 150000004698 iron complex Chemical class 0.000 description 3
- 229940078494 nickel acetate Drugs 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
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- 230000008901 benefit Effects 0.000 description 2
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- 201000011510 cancer Diseases 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- PMGONZDQRPMVRW-UHFFFAOYSA-L copper sulfanide Chemical compound S[Cu]S PMGONZDQRPMVRW-UHFFFAOYSA-L 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 238000002296 dynamic light scattering Methods 0.000 description 2
- 229940044631 ferric chloride hexahydrate Drugs 0.000 description 2
- 235000003891 ferrous sulphate Nutrition 0.000 description 2
- 239000011790 ferrous sulphate Substances 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- NQXWGWZJXJUMQB-UHFFFAOYSA-K iron trichloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].Cl[Fe+]Cl NQXWGWZJXJUMQB-UHFFFAOYSA-K 0.000 description 2
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 2
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 2
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- 239000002245 particle Substances 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 235000014220 Rhus chinensis Nutrition 0.000 description 1
- 240000003152 Rhus chinensis Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000002041 carbon nanotube Substances 0.000 description 1
- 229910021393 carbon nanotube Inorganic materials 0.000 description 1
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000004471 energy level splitting Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 229910021389 graphene Inorganic materials 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- 229960004657 indocyanine green Drugs 0.000 description 1
- MOFVSTNWEDAEEK-UHFFFAOYSA-M indocyanine green Chemical compound [Na+].[O-]S(=O)(=O)CCCCN1C2=CC=C3C=CC=CC3=C2C(C)(C)C1=CC=CC=CC=CC1=[N+](CCCCS([O-])(=O)=O)C2=CC=C(C=CC=C3)C3=C2C1(C)C MOFVSTNWEDAEEK-UHFFFAOYSA-M 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- CWQXQMHSOZUFJS-UHFFFAOYSA-N molybdenum disulfide Chemical compound S=[Mo]=S CWQXQMHSOZUFJS-UHFFFAOYSA-N 0.000 description 1
- AAPCZIZZUJJZAP-UHFFFAOYSA-L nickel(2+) sulfanide Chemical compound S[Ni]S AAPCZIZZUJJZAP-UHFFFAOYSA-L 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- QGLKJKCYBOYXKC-UHFFFAOYSA-N nonaoxidotritungsten Chemical compound O=[W]1(=O)O[W](=O)(=O)O[W](=O)(=O)O1 QGLKJKCYBOYXKC-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 229920000767 polyaniline Polymers 0.000 description 1
- 229920001690 polydopamine Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- ITRNXVSDJBHYNJ-UHFFFAOYSA-N tungsten disulfide Chemical compound S=[W]=S ITRNXVSDJBHYNJ-UHFFFAOYSA-N 0.000 description 1
- 229910001930 tungsten oxide Inorganic materials 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/085—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier conjugated systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Acoustics & Sound (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention discloses a kind of photo-thermal optoacoustic magnetic resonance diagnosis and treatment reagents and preparation method thereof, its interaction using transition metal ions and ligand, change the d electron transitions of transition metal ions, so as to obtain the transient metal complex near infrared absorption, it is diagnosed for photo-thermal therapy and optoacoustic, meanwhile using the paramagnetism of transition metal ions, gained transition metal ions complex can also be used as magnetic resonance imaging contrast medium；Multi-functional diagnosis and treatment reagent in the present invention can be prepared by transition metal precursors solution and ligand solution mixing, and preparation method is very easy, can obtain the multi-functional diagnosis and treatment reagent of photo-thermal optoacoustic magnetic resonance easily and fast, have broad application prospects.
Description
Technical field
This application involves a kind of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagents and preparation method thereof.
Background technology
Cancer is one of principal disease for threatening human health, and early stage Precise Diagnosis is current cancer with high effect nontoxic treatment
The ultimate challenge of disease diagnosis and treatment.In order to improve the therapeutic efficiency of tumour, not only need accurately to detect lesions position, it is also necessary to
Therapeutic effect is monitored, therefore diagnosis and treatment integration is the new trend of oncotherapy.The diagnosis and treatment reported at present are integrated
Means are there are many planting, such as magnetic resonance imaging-photo-thermal therapy（MRI-PTT）, optical imagery-optical dynamic therapy（optical
imaging-PDT）, magnetic resonance imaging-chemotherapy（MRI-Chemotherapy）, photoacoustic imaging-photo-thermal therapy（PAI-PTT）Deng
Deng the application of these diagnosis and treatment integration means be unable to do without the development of diagnosis and treatment reagent.
Diagnosis and treatment reagent is the reagent for integrating imaging and treatment function, common preparation method be will imaging primitive and
Treatment primitive is combined into one by certain connection mode.However the diagnosis and treatment reagent obtained by this method has the obvious disadvantage that,
When they are into complicated vivo environment, imaging primitive and treatment primitive are it is possible that detach, so as to be unfavorable for tumor locus
Accurate diagnosis and treatment.Therefore, develop based on same material both can be as imaging agents but also as the multi-functional of therapeutic reagent
Material is of great significance for the therapeutic efficiency for improving tumour.
Near infrared absorption material has relatively strong absorption in the range of 700-3000 nm, and biological tissue is in this wave band model
It is relatively low to enclose absorption, therefore they have been widely used in biomedical sector.On the one hand, it is generated after absorbing laser using them
Heat pass through photo-thermal therapy（PTT）Achieve the purpose that kill tumour.On the other hand, they absorb the fuel factor that laser generates and may be used also
Cause tissue that thermal expansion occurs, and then send out ultrasonic wave for photoacoustic imaging（PAI）.Therefore, using single near infrared absorption
Photoacoustic imaging-photo-thermal therapy integration can be realized in material, is detached so as to which perfection is solved in imaging primitive and treatment primitive body
The problem of.Moreover, photo-thermal therapy is compared with traditional oncotherapy means, also with some other potential advantage, packet
Include process is easy, specificity is high, normal tissue is not damaged, recovery is fast etc..Meanwhile photoacoustic imaging and traditional optical imagery phase
Than, it may have lower light scattering and higher resolution ratio and sensitivity.Therefore, optoacoustic-photo-thermal diagnosis reagent has extensive
Application prospect.
Current optoacoustic reported in the literature-photo-thermal diagnosis reagent mainly has four major class.The first kind is organic compound, including
Nir dye（Such as indocyanine green）And some high molecular polymers（Such as polyaniline, poly-dopamine）, their photo-thermal turn
It is relatively low to change rate, and photobleaching is serious；Second class is noble metal nanometer material, such as gold nanorods, gold nano grain, their valencys
Lattice are expensive, and cost is higher；Third class is carbon nanomaterial, such as carbon nanotube, graphene；4th class is the oxidation of transition metal
Object and sulfide, such as the nano material of tungsten oxide, tungsten sulfide, molybdenum sulfide.Although rear two classes material photostability or into
This has advantage than preceding two classes material above, is respectively provided with the potentiality for developing into optoacoustic-photo-thermal diagnosis reagent, but they are required for
Complicated preparation and last handling process, limit their application to a certain extent.
Invention content
In view of the above-mentioned problems, an object of the present invention, which is to provide one kind, can be used in tumor thermal therapy, photoacoustic imaging
And the integrated photo-thermal-optoacoustic of diagnosis and treatment-magnetic resonance diagnosis and treatment reagent of magnetic resonance imaging.The reagent can also simultaneously be used as magnetic resonance into
As contrast agent.In general, paramagnetic metal ion has azygous d electronics, when paramagnetic metal ion and ligand are mutual
When effect forms complex, energy level splitting occurs for d tracks in metal ion, and electronics can generate d-d transition, so that it is to spy
The light of standing wave length has certain absorption.Since d-d transition is strongly dependent on the property of ligand, by changing ligand i.e.
Controllable complex is in the visual field even absorption of near infrared region.Using above-mentioned characteristic, by be simply mixed paramagnetic metal from
Sub- precursor solution and ligand compound solution prepare the complex material near infrared absorption, for photo-thermal-light of tumour
Sound-integrated the new method of magnetic resonance diagnosis and treatment.The diagnosis and treatment integration reagent invented can both exist in the form of complex molecule,
Can also exist with nano material, and can make to mutually convert between them by the pH value and temperature for changing system.
The second object of the present invention is to provide a kind of preparation method of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent.
The technical scheme is that：A kind of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent, the diagnosis and treatment reagent is by paramagnetic
Property transition metal ions precursor solution and ligand solution mix, and utilize the phase of paramagnetic transition metal ion precursor and ligand
Interaction changes the d electron transitions of transition metal ions, so as to obtain the paramagnetic transition metal near infrared absorption ability
Complex material；Wherein, the paramagnetic transition metal ion precursor is the soluble-salt of transition metal；The ligand is
Contain the organic compound of group that can be coordinated with paramagnetic metal ion.
Preferably, the diagnosis and treatment reagent by the mol/L of 0.001 mol/L~0.2 paramagnetic transition metal ion precursor
Mixing and in room under conditions of the ligand aqueous solution of the mol/L of aqueous solution and 0.001 mol/L~0.5 is 2.5~8 in pH value of solution
Temperature decentralization sets to 0-forms for 24 hours.Wherein, the molar ratio of paramagnetic transition metal ion precursor and ligand is 5:1~1:5.
Preferably, the soluble-salt of the transition metal includes halide, nitrate, sulfate, the vinegar of transition metal
Hydrochlorate, oxalates or citrate；Wherein, transition metal is the transition metal ions with not pairs of d electronics, including Fe3+,
Fe2+, Mn2+, Ni2+, Cu2+, Cu+ or Co2+.
Preferably, the described group that can be coordinated with paramagnetic metal ion include catechol group, two sulphur alkenyl groups,
Ethylenediamine group, fewrricyanic acid root, ferrocyanic acid root or their deriveding group, the deriveding group are included in catechol base
The group that tumor targeted molecular is formed is modified on group, two sulphur alkenyl groups, ethylenediamine group, fewrricyanic acid root or ferrocyanic acid root.
Preferably, the diagnosis and treatment reagent is deposited as a complex when being mixed under conditions of pH value of solution is 5.0-8
It is in solution；The diagnosis and treatment reagent is scattered in when being mixed under conditions of pH is 2.8-4.9 in the form of nano material
In solution.Complex form and nano material form mutually convert under certain condition, and certain condition refers to the pH value of solution, temperature
Degree, standing time, concentration.
A kind of preparation method of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent, includes the following steps：
（1）Soluble in water, the wherein paramagnetic metal ion precursor concentration by paramagnetic transition metal ion precursor and ligand difference
For the mol/L of 0.001 mol/L~0.2, ligand concentration is the mol/L of 0.001 mol/L~0.5；
（2）Paramagnetic transition metal ion precursor aqueous solution and ligand aqueous solution are uniformly mixed；
（3）The pH value for adjusting mixed solution is 2.5~8；
（4）Mixed solution is placed at room temperature for 0~24 h；
The paramagnetic transition metal ion precursor is the soluble-salt of transition metal；The ligand contains can be with paramagnetism
The group of metallic ion coordination.
Preferably, step（1）In, paramagnetic metal ion precursor concentration is the mol/L of 0.01 mol/L~0.1, and ligand is dense
It spends for the mol/L of 0.01 mol/L~0.1；Step（2）In, paramagnetic transition metal ion precursor and ligand molar ratio are 5:1~
1:5；Step（3）In, the pH value of mixed solution is 3~7；Step（4）In, mixed solution is placed at room temperature for 0~2 h.
Preferably, the soluble-salt of the transition metal includes halide, nitrate, sulfate, the vinegar of transition metal
Hydrochlorate, oxalates or citrate；Wherein, transition metal is the transition metal ions with not pairs of d electronics, including Fe3+,
Fe2+, Mn2+, Ni2+, Cu2+, Cu+ or Co2+.
Preferably, the described group that can be coordinated with paramagnetic metal ion include catechol group, two sulphur alkenyl groups,
Ethylenediamine group, fewrricyanic acid root, ferrocyanic acid root or their deriveding group.The deriveding group is included in catechol base
The group that tumor targeted molecular is formed is modified on group, two sulphur alkenyl groups, ethylenediamine group, fewrricyanic acid root or ferrocyanic acid root.
Preferably, the diagnosis and treatment reagent is deposited as a complex when being mixed under conditions of pH value of solution is 5.0-8
It is in solution；The diagnosis and treatment reagent is scattered in when being mixed under conditions of pH is 2.8-4.9 in the form of nano material
In solution.Complex form and nano material form mutually convert under certain condition, and certain condition refers to the pH value of solution, temperature
Degree, standing time, concentration.
The present invention is changed the d-d transition of metal ion, is made using the interaction between ligand and paramagnetic metal ion
Obtaining gained complex has near infrared absorption, so as to be used for tumor thermal therapy, photoacoustic imaging.
For the present invention as a result of ion centered on paramagnetic metal ion, the complex finally obtained has paramagnetism,
Therefore it can be used as magnetic resonance imaging contrast simultaneously.
Complex of the present invention can be micromolecular compound, can also form complex nano material.It can be by changing
Become the structure of ligand, regulate and control the optical absorption characteristics and existence form in the solution of complex（Small molecule or nanometer
Grain）.The present invention can by adjusting pH, time, concentration control the size of complex nano particle.
The present invention is simply mixed using paramagnetic metal ion precursor solution and ligand solution, you can obtain photo-thermal-optoacoustic-
Magnetic resonance diagnosis and treatment reagent is more simpler than current preparation method reported in the literature.The present invention using paramagnetic metal ion and
Than reaction, obtained photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent is not needed to be further purified, be can be used directly for ligand metering.
If ligand molecular of the present invention modification is upper to molecule of the tumour with targeting, it is final obtain match
Close object also can target tumor, realize the accurate targeting diagnosis and treatment of tumour.
Description of the drawings
The invention will be further described with reference to the accompanying drawings and embodiments：
Fig. 1 is the abosrption spectrogram of 1 gained gallic acid of the embodiment of the present invention-iron complex；
Fig. 2 is 2 gained gallic acid of the embodiment of the present invention-heating curve of the iron complex under 808 nm laser irradiations；
Fig. 3 is the size of hydration distribution map of 3 gained gallic acid of the embodiment of the present invention-iron complex nano particle；
Fig. 4 is the transmission electron microscope photo of 3 gained gallic acid of the embodiment of the present invention-iron complex nano particle；
Fig. 5 is 3 gained gallic acid of the embodiment of the present invention-iron complex nanoparticles solution in 808 nm laser irradiation differences
Between when thermograph；
Fig. 6 is 4 gained gallic acid of the embodiment of the present invention-light of the iron complex nanoparticles solution under 808 nm laser irradiations
Thermal stability；
Fig. 7 is the photoacoustic imaging signal of 5 gained gallic acid of the embodiment of the present invention-iron complex nanoparticles solution various concentration
Figure；
Fig. 8 is the size of hydration variation tendency of 6 gained gallic acid of the embodiment of the present invention-iron complex nano particle；
Fig. 9 is the size of hydration variation tendency of 7 gained gallic acid of the embodiment of the present invention-iron complex nano particle；
Figure 10 is 8 gained dopamine of the embodiment of the present invention-heating curve of the iron complex under 808 nm laser irradiations；
Figure 11 is variation diagram of 8 gained dopamine of the embodiment of the present invention-iron complex photoacoustic signal with concentration；
Figure 12 is the abosrption spectrogram of 9 gained ferroferricyanide complex of the embodiment of the present invention；
Figure 13 increases temperature with concentration for 9 gained ferroferricyanide complex of the embodiment of the present invention under 808 nm laser irradiations
Variation tendency；
Figure 14 is the abosrption spectrogram of 10 gained Malaysia itrile group dimercapto of the embodiment of the present invention-copper (II) complex；
Figure 15 is the abosrption spectrogram of 11 gained polyethyleneimine of the embodiment of the present invention-copper (I) complex；
Figure 16 is the magnetic resonance imaging figure of 13 gained gallic acid of the embodiment of the present invention-iron complex nanoparticles solution.
Specific embodiment
Explain the technical solution of embodiment involved in the present invention in detail below with reference to drawings and examples.
A kind of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent, the diagnosis and treatment reagent are molten by paramagnetic transition metal ion precursor
Liquid and ligand solution mix, and using the interaction of paramagnetic transition metal ion precursor and ligand, change transition metal
The d electron transitions of ion, so as to obtain the paramagnetic transition metal complex material near infrared absorption ability；Wherein, institute
The paramagnetic transition metal ion precursor stated is the soluble-salt of transition metal；The ligand is containing can be with paramagnetic metal
The organic compound of the group of ion coordination.
The diagnosis and treatment reagent by the mol/L of 0.001 mol/L~0.2 paramagnetic transition metal ion precursor aqueous solution
Ligand aqueous solution with the mol/L of 0.001 mol/L~0.5 is mixed under conditions of being 2.5~8 in pH value of solution and is put at room temperature
It sets to 0-forms for 24 hours.Wherein, the molar ratio of paramagnetic transition metal ion precursor and ligand is 5:1~1:5.
The soluble-salt of the transition metal includes but not limited to halide, nitrate, sulfate, the vinegar of transition metal
Hydrochlorate, oxalates, citrate；Wherein, transition metal is the transition metal ions with not pairs of d electronics, including but it is unlimited
In Fe3+, Fe2+, Mn2+, Ni2+, Cu2+, Cu+, Co2+.
The group that can be coordinated with paramagnetic metal ion includes but not limited to catechol group, two sulphur alkenyls
Group, ethylenediamine group, fewrricyanic acid root, ferrocyanic acid root and their deriveding group, the deriveding group are included in adjacent benzene two
The base that tumor targeted molecular is formed is modified on phenolic group group, two sulphur alkenyl groups, ethylenediamine group, fewrricyanic acid root or ferrocyanic acid root
Group.
The diagnosis and treatment reagent is present as a complex when being mixed under conditions of pH value of solution is 5.0-8 in solution
In；The diagnosis and treatment reagent is scattered in the form of nano material in solution when being mixed under conditions of pH is 2.8-4.9.Match
Solvate form and nano material form mutually convert under certain condition, when certain condition refers to the pH value, temperature, placement of solution
Between, concentration.
A kind of preparation method of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent, includes the following steps：
（1）Soluble in water, the wherein paramagnetic metal ion precursor concentration by paramagnetic transition metal ion precursor and ligand difference
For the mol/L of 0.001 mol/L~0.2, the mol/L of preferably 0.01 mol/L~0.1, ligand concentration is 0.001 mol/L~0.5
The mol/L of mol/L, preferably 0.01 mol/L~0.1；
（2）By paramagnetic transition metal ion precursor aqueous solution and ligand according to molar ratio 5:1~1:5 are uniformly mixed；
（3）The pH value for adjusting mixed solution is 2.5~8, and preferable ph is 3~7；
（4）Mixed solution is placed at room temperature for 0~24 h, is preferably placed at room temperature for 0~2 h；
The paramagnetic transition metal ion precursor is the soluble-salt of transition metal；The ligand contains can be with paramagnetism
The group of metallic ion coordination.
The soluble-salt of the transition metal includes but not limited to halide, nitrate, sulfate, the vinegar of transition metal
Hydrochlorate, oxalates, citrate；Wherein, transition metal is the transition metal ions with not pairs of d electronics, including but it is unlimited
In Fe3+, Fe2+, Mn2+, Ni2+, Cu2+, Cu+, Co2+.
The group that can be coordinated with paramagnetic metal ion includes but not limited to catechol group, two sulphur alkenyls
Group, ethylenediamine group, fewrricyanic acid root, ferrocyanic acid root and their deriveding group, the deriveding group are included in adjacent benzene two
The base that tumor targeted molecular is formed is modified on phenolic group group, two sulphur alkenyl groups, ethylenediamine group, fewrricyanic acid root or ferrocyanic acid root
Group.
The diagnosis and treatment reagent is present as a complex when being mixed under conditions of pH value of solution is 5.0-8 in solution
In；The diagnosis and treatment reagent is scattered in the form of nano material in solution when being mixed under conditions of pH is 2.8-4.9.Match
Solvate form and nano material form mutually convert under certain condition, when certain condition refers to the pH value, temperature, placement of solution
Between, concentration.
Embodiment 1
Ferric chloride hexahydrate and gallic acid are dissolved in deionized water respectively, be made into respectively 0.01 M ferric chloride solution and
The gallic acid solution of 0.015 M.Then 5 mL ferric chloride solutions with 5 mL gallic acid solution are mixed, are adjusted with NaOH molten
Liquid pH value obtains gallic acid-iron complex to 7.0, absorption spectrum as shown in Figure 1, as can be seen from the figure nutgall
Acid-iron complex has stronger absorption near infrared region.
Embodiment 2
The 0.01 M ferric chloride solutions of 5 mL with the 0.015 M gallic acid solution of 5 mL are mixed, solution is adjusted with NaOH
PH value obtains gallic acid-iron complex, 1 mM is diluted to deionized water, then wherein 0.5 mL solution is taken to put to 7.0
In plastic centrifuge tube, place it under the 808 nm laser that power density is 0.5 W/cm2 and be irradiated, while with 0.5 mL
As a comparison, attached drawing 2 is change curve of the solution temperature with irradiation time to deionized water, from the figure, it can be seen that with irradiation
The extension of time, the temperature of gallic acid-iron complex solution gradually rises, and the temperature of deionized water is basically unchanged, explanation
Gallic acid-iron complex has good photothermal conversion effect.
Embodiment 3
The 0.01 M ferric chloride solutions of 5 mL with the 0.015 M gallic acid solution of 5 mL are mixed, solution is adjusted with NaOH
Mixed solution is placed 2 h, can obtain gallic acid-iron complex nano particle by pH value at room temperature again to 3.7.Attached drawing 3 is
The size of hydration distribution map of gained nano particle in the solution, average size of hydration is about 45 nm.Attached drawing 4 is gained nanometer
The transmission electron microscope photo of grain, average-size is about 43 nm.Gained gallic acid-iron complex nano particle is diluted to 1.5
MM takes wherein 0.5 mL solution to be placed under the 808 nm laser that power density is 0.5 W/cm2 and is irradiated, while with 0.5 mL
Deionized water as a comparison, attached drawing 5 be irradiate the heat of gallic acid-iron complex nanoparticles solution and water under different time into
As figure, it can be seen from the figure that gallic acid-iron complex nano particle has good photothermal conversion effect.
Embodiment 4
The 0.01 M ferric chloride solutions of 5 mL with the 0.015 M gallic acid solution of 5 mL are mixed, solution is adjusted with NaOH
Mixed solution is placed 2 h, can obtain gallic acid-iron complex nano particle by pH value at room temperature again to 3.7.By gained
Gallic acid-iron complex nano particle is diluted to 1.5 mM, and wherein 0.5 mL solution is taken to be placed in power density as 0.5 W/cm2
808 nm laser under be irradiated, be cooled to room temperature after ten minutes, be then irradiated again, so cycle 5 times, attached drawing 6
To irradiate the heating curve of 5 solution, it can be seen from the figure that gallic acid-iron complex nano particle has good light
Thermal stability.
Embodiment 5
The 0.01 M ferric chloride solutions of 5 mL with the 0.015 M gallic acid solution of 5 mL are mixed, solution is adjusted with NaOH
Mixed solution is placed 2 h, can obtain gallic acid-iron complex nano particle by pH value at room temperature again to 3.7.By gained
Gallic acid-iron complex nano particle is diluted to various concentration, it is tested using multispectral optoacoustic dislocation scanning and imaging system
Photoacoustic signal, attached drawing 7 for various concentration gallic acid-iron complex nanoparticles solution photoacoustic imaging figure and they
Corresponding photoacoustic signal value, it can be seen from the figure that gallic acid-iron complex nano particle is imitated with good photoacoustic imaging
Fruit.
Embodiment 6
The 0.01 M ferric chloride solutions of 5 mL with the 0.015 M gallic acid solution of 5 mL are mixed, obtain gallic acid-iron
Complex adjusts solution ph to 3.7 with NaOH, then places at room temperature, and point sampling in different times, using dynamic
Light scattering apparatus tests the size of hydration of particles in solution.Attached drawing 8 is the hydration of gallic acid-iron complex nano particle in solution
Size changes with time trend, and with the extension of standing time, the size of gallic acid-iron complex nano particle gradually increases
Add, illustrate that the size of nano particle can be controlled by controlling the standing time of solution.
Embodiment 7
The 0.01 M ferric chloride solutions of 5 mL with the 0.015 M gallic acid solution of 5 mL are mixed, obtain gallic acid-iron
Complex adjusts solution ph to 4.5 with NaOH, then places at room temperature, and point sampling in different times, using dynamic
Light scattering apparatus tests the size of hydration of particles in solution.Attached drawing 9 is the hydration of gallic acid-iron complex nano particle in solution
Size changes with time trend, compared with Example 6, increases pH value, can slow down the growth rate of nanoparticle size.If
Solution ph is further increased to more than 5.5, then gallic acid-iron complex nano particle will not be formed in solution.
Embodiment 8
Ferric chloride hexahydrate and Dopamine hydrochloride are dissolved in deionized water respectively, be made into respectively the ferric chloride solution of 0.01 M with
And 0.03 M Dopamine hydrochloride solution.Then 5 mL ferric chloride solutions are mixed with 5 mL gallic acid solution, with NaOH tune
Solution ph is saved to 7.0, obtains dopamine-iron complex.Dopamine-iron complex solution is diluted to various concentration, respectively
Take 0.5 mL be placed in power density be 0.5 W/cm2 808 nm laser under be irradiated, attached drawing 10 for various concentration dopamine-
Iron complex solution temperature with irradiation time change curve.Attached drawing 11 is the photoacoustic signal value of dopamine-iron complex solution
With the variation tendency of concentration.
Embodiment 9
Ferrous sulfate and the potassium ferricyanide are dissolved in deionized water respectively, are made into the ferric chloride solution and 0.01 M of 0.01 M respectively
Dopamine hydrochloride solution.Then 3 mL ferrous sulfate solutions with 2 mL potassium ferricyanide solutions are mixed, obtain ferroferricyanide
Solution, absorption spectrum as shown in Figure 12, as can be seen from the figure ferroferricyanide complex near infrared region have compared with
Strong absorption.Attached drawing 13 is ferroferricyanide solution in the 808 nm laser irradiations 10 minutes of 0.5 W/cm2, temperature change value
With the variation tendency of concentration.
Embodiment 10
Nitrification copper and dimercapto Maleic nitrile disodium are dissolved in deionized water respectively, are made into the nitrification copper solution of 0.01 M respectively
And 0.01 M two sodium solution of dimercapto Maleic nitrile.Then by 5 mL copper nitrate solutions and 10 mL dimercapto Maleic nitrile disodiums
Solution mixes, and obtains Malaysia itrile group dimercapto-copper (II) complex solution, absorption spectrum as shown in Figure 14, can from figure
To find out that Malaysia itrile group dimercapto-copper (II) complex has stronger absorption near infrared region.
Embodiment 11
Cuprous iodide is dissolved in the liquor kalii iodide of 2 M, is made into the cuprous iodide solution of 10 mM.It is 8000 by molecular weight
Polyethyleneimine is dissolved in deionized water, is made into the aq. polyethyleneimine of 5 mg/mL.By 1 mL cuprous iodides solution and 9
ML polyethylenimine solutions mix, and obtain polyethyleneimine-copper (I) complex solution, absorption spectrum is as shown in Figure 15.
Embodiment 12
Nickel acetate and dimercapto Maleic nitrile disodium are dissolved in deionized water, are made into the nickel acetate solution and 20 mM of 10 mM respectively
Two sodium solution of dimercapto Maleic nitrile.5 mL nickel acetate solutions with 5 mL dimercaptos Maleic nitrile, two sodium solution are mixed, obtain Malaysia
Itrile group dimercapto-nickel (II) complex solution can be used as optoacoustic-photo-thermal diagnosis reagent.
Embodiment 13
The 0.01 M ferric chloride solutions of 5 mL with the 0.015 M gallic acid solution of 5 mL are mixed, solution is adjusted with NaOH
Mixed solution is placed 2 h, obtains gallic acid-iron complex nano particle by pH value at room temperature again to 3.7.Gained is not eaten
Sub- acid-iron complex nano particle is diluted to various concentration, tests its magnetic resonance with 3T magnetic resonance imaging systems using clinic and makes
Shadow effect.The T1 magnetic resonance imaging figures of gallic acid-iron complex nanoparticles solution when attached drawing 16 is various concentration, from figure
As can be seen that in the presence of gallic acid-iron complex nano particle, T1 magnetic resonance image significantly brightens, and explanation does not have
Gallate-based-iron complex nano particle has preferable T1 magnetic resonance effect.
Adjusting pH value can be used hydrochloric acid, sodium hydroxide, sodium carbonate, sodium bicarbonate, PBS and delays according to actual needs in the present invention
Rush solution, HEPES buffer solutions, NaAc_HAc buffer solution etc..
The present invention can regulate and control the optical absorption characteristics of complex by changing the type of ligand.
The present invention can be by adjusting mixed solution pH, mixed solution standing time, paramagnetic metal ion precursor solution
The size of complex nano particle is controlled with ligand solution concentration.
The present invention is changed the d-d transition of metal ion, is made using the interaction between ligand and paramagnetic metal ion
Obtaining gained complex has near infrared absorption ability, so as to be used for tumor thermal therapy, photoacoustic imaging.As a result of suitable
Ion centered on magnetic metal ion, the complex finally obtained has paramagnetism, therefore can be made simultaneously as magnetic resonance imaging
Shadow agent.
The present invention is simply mixed using paramagnetic metal ion precursor solution and ligand solution, you can obtain photo-thermal-optoacoustic-
Magnetic resonance diagnosis and treatment reagent is more simpler than current preparation method reported in the literature.
If ligand molecular of the present invention modification is upper to molecule of the tumour with targeting, it is final obtain match
Close object also can target tumor, realize the accurate targeting diagnosis and treatment of tumour.
The present invention is using paramagnetic metal ion and ligand metering than reaction, obtained photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment
Reagent does not need to be further purified, and can be used directly.
It the above is only the concrete application example of the present invention, protection scope of the present invention be not limited in any way.Except above-mentioned
Outside embodiment, the present invention can also have other embodiment.All technical solutions formed using equivalent substitution or equivalent transformation,
It falls within scope of the present invention.
Claims (10)
1. a kind of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent, it is characterised in that：The diagnosis and treatment reagent is by paramagnetic transition metal
Ion precursor solution and ligand solution mix, and using the interaction of paramagnetic transition metal ion precursor and ligand, change
Become the d electron transitions of transition metal ions, so as to obtain the paramagnetic transition metal complex material near infrared absorption ability
Material；Wherein, the paramagnetic transition metal ion precursor is the soluble-salt of transition metal；The ligand is containing can be with
The organic compound of the group of paramagnetic metal ion coordination.
A kind of 2. photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent according to claim 1, which is characterized in that the diagnosis and treatment examination
Paramagnetic transition metal ion precursor aqueous solution and 0.001 mol/L~0.5 of the agent by the mol/L of 0.001 mol/L~0.2
The ligand aqueous solution of mol/L mixes under conditions of being 2.5~8 in pH value of solution and places 0-24h at room temperature and forms.
A kind of 3. photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent according to claim 1 or 2, which is characterized in that the mistake
The soluble-salt for crossing metal includes halide, nitrate, sulfate, acetate, oxalates or the citrate of transition metal；Its
In, transition metal is the transition metal ions with not pairs of d electronics, including Fe3+, Fe2+, Mn2+, Ni2+, Cu2+, Cu+ or
Co2+。
4. a kind of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent according to claim 2, which is characterized in that it is described can with it is suitable
The group of magnetic metal ion coordination includes catechol group, two sulphur alkenyl groups, ethylenediamine group, fewrricyanic acid root, ferrous cyanogen
Acid group or their deriveding group, the deriveding group be included in catechol group, two sulphur alkenyl groups, ethylenediamine group,
The group that tumor targeted molecular is formed is modified on fewrricyanic acid root or ferrocyanic acid root.
5. a kind of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent according to claim 1 or 2, which is characterized in that described examines
Reagent is treated to be present as a complex in solution when mixing under conditions of pH value of solution is 5.0-8；The diagnosis and treatment examination
Agent is scattered in the form of nano material in solution when being mixed under conditions of pH is 2.8-4.9.
A kind of 6. preparation method of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent according to claim 1, which is characterized in that packet
Include following steps：
（1）Soluble in water, the wherein paramagnetic metal ion precursor concentration by paramagnetic transition metal ion precursor and ligand difference
For the mol/L of 0.001 mol/L~0.2, ligand concentration is the mol/L of 0.001 mol/L~0.5；
（2）Paramagnetic transition metal ion precursor aqueous solution and ligand aqueous solution are uniformly mixed；
（3）The pH value for adjusting mixed solution is 2.5~8；
（4）Mixed solution is placed at room temperature for 0~24 h；
The paramagnetic transition metal ion precursor is the soluble-salt of transition metal；The ligand contains can be with paramagnetism
The group of metallic ion coordination.
7. a kind of preparation method of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent according to claim 6, which is characterized in that
Step（1）In, paramagnetic metal ion precursor concentration is the mol/L of 0.01 mol/L~0.1, ligand concentration 0.01
The mol/L of mol/L~0.1；
Step（2）In, paramagnetic transition metal ion precursor and ligand molar ratio are 5:1~1:5；
Step（3）In, the pH value of mixed solution is 3~7；
Step（4）In, mixed solution is placed at room temperature for 0~2 h.
8. a kind of preparation method of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent described according to claim 6 or 7, feature exist
In the soluble-salt of, the transition metal include the halide of transition metal, nitrate, sulfate, acetate, oxalates or
Citrate；Wherein, transition metal is the transition metal ions with not pairs of d electronics, including Fe3+, Fe2+, Mn2+, Ni2
+, Cu2+, Cu+ or Co2+.
9. a kind of preparation method of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent described according to claim 6 or 7, feature exist
In, the described group that can be coordinated with paramagnetic metal ion include catechol group, two sulphur alkenyl groups, ethylenediamine group,
Fewrricyanic acid root, ferrocyanic acid root or their deriveding group, the deriveding group are included in catechol group, two sulphur alkenyls
The group that tumor targeted molecular is formed is modified on group, ethylenediamine group, fewrricyanic acid root or ferrocyanic acid root.
10. a kind of preparation method of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent according to claim 6, which is characterized in that
The diagnosis and treatment reagent is present as a complex when being mixed under conditions of pH value of solution is 5.0-8 in solution；It is described
Diagnosis and treatment reagent be scattered in solution in the form of nano material when pH is mixes under conditions of 2.8-4.9.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111358949A (en) * | 2020-04-12 | 2020-07-03 | 广西师范大学 | Preparation and application of targeted anti-tumor iron (III) -based nano material |
| CN112704735A (en) * | 2020-12-22 | 2021-04-27 | 山西大学 | Inorganic ion mediated organic compound nano enzyme, preparation method and application |
| CN113713097A (en) * | 2021-09-16 | 2021-11-30 | 南通大学 | Tumor photothermal-photodynamic combined treatment nano-drug and preparation method and application thereof |
| CN114732946A (en) * | 2022-03-14 | 2022-07-12 | 中山大学附属第七医院(深圳) | Calcium-based biological material and preparation method and application thereof |
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2018
- 2018-02-28 CN CN201810166627.2A patent/CN108187048A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111358949A (en) * | 2020-04-12 | 2020-07-03 | 广西师范大学 | Preparation and application of targeted anti-tumor iron (III) -based nano material |
| CN112704735A (en) * | 2020-12-22 | 2021-04-27 | 山西大学 | Inorganic ion mediated organic compound nano enzyme, preparation method and application |
| CN113713097A (en) * | 2021-09-16 | 2021-11-30 | 南通大学 | Tumor photothermal-photodynamic combined treatment nano-drug and preparation method and application thereof |
| CN114732946A (en) * | 2022-03-14 | 2022-07-12 | 中山大学附属第七医院(深圳) | Calcium-based biological material and preparation method and application thereof |
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Application publication date: 20180622 |