CN107383252A - Polymer for quaternary quantum dot phase transfer and its preparation method and application - Google Patents
Polymer for quaternary quantum dot phase transfer and its preparation method and application Download PDFInfo
- Publication number
- CN107383252A CN107383252A CN201710252430.6A CN201710252430A CN107383252A CN 107383252 A CN107383252 A CN 107383252A CN 201710252430 A CN201710252430 A CN 201710252430A CN 107383252 A CN107383252 A CN 107383252A
- Authority
- CN
- China
- Prior art keywords
- quantum dot
- polymer
- high molecular
- preparation
- dmso
- 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.)
- Pending
Links
- 239000002096 quantum dot Substances 0.000 title claims abstract description 69
- 229920000642 polymer Polymers 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 238000012546 transfer Methods 0.000 title abstract description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 39
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 9
- 239000007788 liquid Substances 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 229920002521 macromolecule Polymers 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 238000001556 precipitation Methods 0.000 claims description 5
- VHSHLMUCYSAUQU-UHFFFAOYSA-N 2-hydroxypropyl methacrylate Chemical compound CC(O)COC(=O)C(C)=C VHSHLMUCYSAUQU-UHFFFAOYSA-N 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- -1 sulfuryl amine Chemical class 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 3
- 239000003495 polar organic solvent Substances 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 238000005119 centrifugation Methods 0.000 claims description 2
- 238000010511 deprotection reaction Methods 0.000 claims description 2
- 125000001033 ether group Chemical group 0.000 claims description 2
- UQUPIHHYKUEXQD-UHFFFAOYSA-N n,n′-dimethyl-1,3-propanediamine Chemical compound CNCCCNC UQUPIHHYKUEXQD-UHFFFAOYSA-N 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- SHLDRGRIHSAHQU-UHFFFAOYSA-N C(O)(O)=O.C(OC(C)(C)C)(OC(C)(C)C)=O Chemical compound C(O)(O)=O.C(OC(C)(C)C)(OC(C)(C)C)=O SHLDRGRIHSAHQU-UHFFFAOYSA-N 0.000 claims 1
- 241000255964 Pieridae Species 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 239000005864 Sulphur Substances 0.000 claims 1
- 150000008065 acid anhydrides Chemical class 0.000 claims 1
- 229960003237 betaine Drugs 0.000 claims 1
- 239000003054 catalyst Substances 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims 1
- 239000002105 nanoparticle Substances 0.000 abstract description 11
- 150000001875 compounds Chemical class 0.000 abstract description 10
- 210000000865 mononuclear phagocyte system Anatomy 0.000 abstract description 8
- 150000003384 small molecules Chemical class 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 4
- 230000003647 oxidation Effects 0.000 abstract description 3
- 238000007254 oxidation reaction Methods 0.000 abstract description 3
- 238000004873 anchoring Methods 0.000 abstract description 2
- 230000001105 regulatory effect Effects 0.000 abstract description 2
- 238000002474 experimental method Methods 0.000 description 13
- 239000003814 drug Substances 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000003446 ligand Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 239000002202 Polyethylene glycol Substances 0.000 description 7
- 229920001223 polyethylene glycol Polymers 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000002245 particle Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000002086 nanomaterial Substances 0.000 description 2
- 239000013110 organic ligand Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000006862 quantum yield reaction Methods 0.000 description 2
- 150000003839 salts Chemical group 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 150000008053 sultones Chemical class 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical class CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000005034 decoration Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 238000000695 excitation spectrum Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000002444 silanisation Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229910001428 transition metal ion Inorganic materials 0.000 description 1
- 230000010148 water-pollination Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
- C08F8/30—Introducing nitrogen atoms or nitrogen-containing groups
- C08F8/32—Introducing nitrogen atoms or nitrogen-containing groups by reaction with amines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/02—Use of particular materials as binders, particle coatings or suspension media therefor
- C09K11/025—Use of particular materials as binders, particle coatings or suspension media therefor non-luminescent particle coatings or suspension media
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
- C09K11/88—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing selenium, tellurium or unspecified chalcogen elements
- C09K11/881—Chalcogenides
- C09K11/883—Chalcogenides with zinc or cadmium
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Biomedical Technology (AREA)
- Polymers & Plastics (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides a kind of polymer for quaternary quantum dot phase transfer, is three block high-molecular compound that hydrophilic radical is prepared by anchoring group, sulfobetaines of azacyclo-, and preparation method of the present invention is simple, is adapted to industrialize.The present invention is good in quaternary quantum dot phase transfer effect, improves the shortcomings that sulfydryl small molecule is easy to oxidation；On the one hand substitute oxidizable PEG using its " biology is stealthy " function simultaneously, quantum dot nano particle is set to escape the capture of reticuloendothelial system, on the other hand quantum dot surface electric charge is assigned, by the way that the number of surface charge and strong and weak regulated and controled, the size adjustable of quantum dot nano particle is realized, further influences its internal distribution；And make the quantum dot nano compound of structure that there is preferable biocompatibility and modifiability.
Description
Technical field
The present invention relates to field of nanometer material technology, and in particular to a kind of high molecular polymerization for quaternary quantum dot phase transfer
Thing and its preparation method and application.
Background technology
Quantum dot, compared to traditional organic dyestuff, has excitation spectrum as a kind of new fluorescent nano material
It is wide, the advantages that emission spectrum is narrow and adjustable, resistance to photobleaching, and fluorescence quantum yield is high, glimmering in current biological fluorescent labelling and chemistry
Great development potentiality in light probe.The high quality quantum dot being commonly used, synthesized using the organic method of high temperature, it is such a
Synthetic method makes quantum dot be rich in oil-soluble part, limits its application in the association area such as biology and medicine and pharmacology.Will
Oil-soluble quantum dot studies its phase transition behavior, phase transfer is detected using autofluorescence as a kind of model of hydrophobic drug
Efficiency, be a kind of more directly perceived and cost-effective measure；Meanwhile using oil-soluble quantum dot as a kind of pharmaceutical carrier, profit
With the fluorescent characteristic of its own, a kind of effective means are provided for the DYNAMIC DISTRIBUTION of research medicine in vivo.Therefore, to oil
Dissolubility quantum dot carries out phase transfer, makes it have good biocompatibility, is that the one kind for realizing hydrophobic drug phase transfer has
Imitate simulation meanses and measure, and one of focus for being studied as pharmaceutical carrier in pharmaceutical field of quantum dot.
Realize that the water miscible method of quantum dot there are two classes：One is in the preparation of quantum dot, direct synthesis in water quantum
Point, but because water boiling point is relatively low, by the quantum dot for the synthesis that flows back, without being clearly nucleated and growing boundary, cause quantum dot
Crystal formation it is poor, surface defect is obvious, fluorescence quantum yield is low, half-peak breadth is wider and less stable；Another method is then
Oil-soluble quantum dot is exchanged by the organic ligand on surface, the measure such as amphipathy macromolecule material wraps up, using phase transfer
Method realize the water solubility of quantum dot, its main means has：(1) hydride modified method, silanization are to Nanoparticle Modified
Common method, i.e., quantum dot is coated by silica, makes quantum dot that there is water-soluble and modifiability；(2) match somebody with somebody
Body exchange process, i.e., using the organic ligand of suitable ligand substituting quantum dot surface, the quantum dot that such a method obtains has
Less change of size, but the coordinating group due to using causes the quantum dot easily to aoxidize often for sulfydryl, stability compared with
Difference；Simultaneously because such a part is usually small molecule, lack further modifiability, limit the biologic applications of quantum dot；
(3) macromolecule pack, i.e., by with amphipathic polymer, wrapping up quantum dot, making quantum dot on the one hand have
Water solubility, on the other hand because polymer is that one kind has multi-functional complicated molecule, it can further be repaiied
Decorations reach multi-level application of the quantum dot in biology or medicine and pharmacology.This method not only makes oil-soluble quantum dot in biocycle
It is compatible and be stabilized in border, can be with large biological molecule or medicine as well as possessing in corresponding part and high polymer material
The group that thing is combined, so that the quantum dot with excellent photoluminescent property is applied to biomedical imaging and internal medicine is supervised
Survey etc. is multi-field, but high molecular polymer is come real by the mutual hydrophobic effect of long alkane interchain with oil-soluble quantum dot
Existing, its obtained water-soluble quantum dot has a larger volume, and the quantum wrapped up is counted out uncertainty, the amount of limiting
Application of the son point in terms of biomarker and pharmaceutical carrier.
Meanwhile quantum dot possesses the characteristics of nano-particle is distributed in vivo, nano-particle exists as a kind of nano material
Easily captured in vivo by reticuloendothelial system (RES), so that it loses desired effect, measure universal at present is
Using polyethylene glycol (PEG) modify, PEG be it is a kind of it is neutral, nontoxic, hydrophily is higher, the polymer of non-immunogenic, can have
Effect avoids acting on immunoglobulin, hinders the bonding of particle and phagocyte, escapes the capture of reticuloendothelial system, prolong
The residence time of long nano-particle in vivo, but the nano-particle of its PEG modifications is to transition metal ions sensitivity and easily by oxygen
Change, therefore need badly and find a kind of PEG substitute to solve the problems, such as that nano-particle is captured by reticuloendothelial system.
The content of the invention
In order to solve the problems of the prior art, according to the first aspect of the invention, it is an object of the invention to provide one
Kind high molecular polymer, the polymer carry out profit phase inversion to oil-soluble quantum dot by way of macromolecule ligand exchange, made
On the one hand the water-soluble quantum dot of acquisition possesses photoluminescent property stabilization, particle diameter is adjustable, can modify the features such as strong；On the other hand assign
The property such as the escape of its reticuloendothelial system and specific targeting is given, extends its residence time and enhancing biological targeting in vivo
Property, further carry out biomedical applications.
The object of the present invention is achieved like this：
A kind of high molecular polymer, there is following structural formula：
Wherein a=1~15, b=1~15, n=5~33.
The present invention has synthesized a kind of A-B-C three blocks high-molecular compound (as shown in above formula), and wherein A is anchoring group,
B is skeleton structure, and C is water-wet side；It is advantageous that：(1) it instead of conventional mercapto using the more preferable azacyclo- of biocompatibility
Base small molecule is combined as A ends coordinating group and quaternary quantum dot, improves the shortcomings that sulfydryl small molecule is easy to oxidation；
(2) by the use of the sulfobetaines of inner salt form as hydrophilic C-terminal group, on the one hand substituted using its " biology is stealthy " function easy
The PEG of oxidation, quantum dot nano particle is escaped the capture of reticuloendothelial system, on the other hand assign quantum dot surface
Electric charge, by regulating and controlling the number of surface charge and strong and weak, the size adjustable of quantum dot nano particle is realized, further influences it
Internal distribution；(3) the quantum dot nano compound of structure is made have preferably as B skeleton structures using HPMA
Biocompatibility and modifiability.Secondly using the A-B-C three blocks high-molecular compound as ligand exchanger, by oil-soluble
Quaternary quantum dot carries out profit phase transfer as hydrophobic model.Finally, using structure water-soluble quantum dot carry out cell and
Animal imaging research, evaluate the value of its biomedical applications.
According to the second aspect of the invention, it is an object of the invention to provide the preparation method of above-mentioned high molecular polymer.
The preparation method of above-mentioned high molecular polymer, using following steps：
(1) preparation of sulfobetaines：
By to N, the free-NH of N- dimethyl -1,3- propane diamine (DMPDA)2Protection, sulfuryl amine and deprotection
Prepare sulfobetaines；
(2) preparation of polymer：
With fatty amido-azacyclo- (A), HPMA (B), sulfobetaines (C) for raw material, EDC/NHS is catalysis
Agent, react and high molecular polymer of the present invention is made.
Preferably, in above-mentioned steps (1), dissociate-NH2Blocking group be di-tert-butyl dicarbonate ((Boc)2O)。
Preferably, in above-mentioned steps (1), sulfuryl amine reagent is the sultone of 1,3- third.
Preferably, in above-mentioned steps (1), reaction reagent is anhydrous reagent.
Preferably, in above-mentioned steps (2), fatty amido-azacyclo- (A), HPMA (B), sulfobetaines
(C) mol ratio is：1∶1∶2、1∶1∶1.
Preferably, in above-mentioned steps (2), reaction dissolvent is dimethyl sulfoxide (DMSO) (DMSO), and the reaction time is 5h or so,
After completion of the reaction, add small polar organic solvent recrystallization and filter to obtain high molecular polymer of the present invention.
Preferably, in above-mentioned steps (2), recrystallization solvent is ether, ethyl acetate or petroleum ether.
According to the third aspect of the invention we, it is an object of the invention to provide above-mentioned high molecular polymer in oil-soluble amount
Application in son point phase inversion.
Application of the above-mentioned high molecular polymer in oil-soluble quantum dot phase inversion, using following steps：
Step 1: high molecular polymer of the present invention is dissolved in dimethyl sulfoxide (DMSO) (DMSO), A liquid is made；
Step 2: after oil-soluble quaternary quantum dot is utilized into ethanol purification, it is scattered in chloroform, B liquid is made；
Step 3: A drops are entered in B liquid, after reaction forms homogeneous phase solution, acetone/n-hexane mixed solution precipitation is added
Centrifugation, the precipitation of acquisition is water-soluble quantum dot.
Preferably, in step 1, DMSO temperature is 25~50 DEG C.
Preferably, in step 2, oil-soluble quaternary quantum dot is CuZnInSe/ZnS or AgZnInSe/ZnS；Chloroform
Volume be 1~3mL.
Preferably, in step 3, reaction temperature is 45~70 DEG C；Reaction time is 5~7h；Acetone/n-hexane mixing
The ratio of solution is：Acetone/n-hexane (V/V)=1: 1.
Beneficial effect：
The advantages of present invention is by integrating ligand exchange method and macromolecule pack, part friendship can be carried out by devising one kind
The high-molecular compound changed, using macromolecule ligand exchange process, changed using quantum dot by the relatively small particle after ligand exchange
And high molecular polymer can be modified the characteristics of strong, phase inversion is carried out to quaternary quantum dot.On the one hand utilizing more has biofacies
The azacyclo- of capacitive instead of more oxidizable sulfydryl small molecule as coordinating group, is combined with quaternary quantum dot；And profit
With PEG of the sulfobetaines substitution of inner salt form with " physiology is stealthy " function, quantum dot surface is set to possess multi-charge property
And escape the property of reticuloendothelial system capture；On the other hand instead of by the way of Polymeric ligands exchange traditional
Smaller ligand exchanges, and the quantum dot after phase inversion is had stronger modifiability, stability and self assembly performance, passes through
Further combined with bioactive molecule or medicine, it is carried out to intend in the cell imaging experiment and organism of physiological environment
Histoorgan imaging experiment is studied, and determines the biocompatibility after its phase inversion, can be widely applied for quantum dot with glimmering in vivo
Biology and medicine drug development field based on light probe and drug targeting detection, insoluble drug release tracer.Prepared by the present invention
Water-soluble quantum dot photoluminescent property is good, has good stability and surface is rich in-COOH, can further be coupled containing-NH2 or-
OH bioactive molecule such as antibody, nucleic acid, amino acid etc., can also connect the medicine containing amino；Prepared water solubility
Favorable dispersibility of the quantum dot in buffer system, and can be with the spontaneous nano-complex for being assembled into certain particle diameter, wherein grain
Particle of the footpath between 50-200nm has good EPR effects, is advantageous to increase the passive targeting of nano-particle, is easy to
Tumor research in organism.
Brief description of the drawings：
High molecular polymers (PPZ) of the Fig. 1 prepared by embodiment 5 is to purple before and after CuZnInSe/ZnS quantum dot phase inversions
Outer absorption collection of illustrative plates；
High molecular polymers (PPZ) of the Fig. 2 prepared by embodiment 5 is to glimmering before and after CuZnInSe/ZnS quantum dot phase inversions
Light launches collection of illustrative plates；
High molecular polymers (PPZ) of the Fig. 3 prepared by embodiment 5 is to Electronic Speculum after CuZnInSe/ZnS quantum dot phase inversions
Photo.
Embodiment
The present invention is specifically described below by specific embodiment, it is pointed out here that following examples are served only for this
Invention is further described, it is impossible to is interpreted as limiting the scope of the invention, the person skilled in the art of this area can be with
Some nonessential modifications and adaptations are made to the present invention according to foregoing invention content.All raw materials of the present invention and reagent are
Commercially available prod.
Embodiment 1
The synthesis of sulfobetaines
DB synthesis：
Experimental procedure：
By N, after N- dimethyl -1,3- propane diamine (7.95mmol) is dissolved in 20mL dioxane, 0 DEG C is cooled to, N2Protection
Under conditions of, di-tert-butyl dicarbonate (11.92mmol) is injected, is slowly increased to room temperature, reaction is overnight；After being spin-dried for dioxane,
After adding 20mL distilled water, ethyl acetate extraction, anhydrous sodium sulfate drying, yellow oil is obtained after being spin-dried for.
DBSP synthesis：
Experimental procedure：
After DB (6mmol) is dissolved in into 10mL dimethylformamides, adds the sultone of 1,3- third (9mmol) and react 48 hours
Afterwards, 50mL ether crystallizations are added, after precipitation is dissolved in into dichloromethane, are spin-dried for obtaining yellow oil.
DSP synthesis：
Experimental procedure：
After DBSP is used for into dichloromethane, the dioxane solution of hydrochloric acid is added at 0 DEG C, and is reacted 2 hours in 0 DEG C, is treated
Reaction terminates, and after being spin-dried for reaction solution, adds dichloromethane, isopropanol, the mixed solvent of methanol and is recrystallized, obtain white oil
Shape thing, the grease slowly crystallize into white solid.
Case study on implementation 2
The preparation (imidazole ring) of A-B-C three block compounds：
HPZ synthesis：
Experimental procedure：
After 0.385g HPMAs are dissolved in into 4mL dimethyl sulfoxide (DMSO)s, the dimethyl for being separately added into DSP and histidine is sub-
Sulfolane solution 1mL, 45 DEG C of reactions overnight, precipitate in acetone, filter to obtain white powder HPZ.
Case study on implementation 3
The preparation (pyridine ring) of A-B-C three block compounds
PPZ synthesis：
Experimental procedure：
With case study on implementation 2.
Case study on implementation 4
The preparation of A-B-C1-RGD three block compounds
Experimental procedure：
After HPZ is dissolved in into dimethyl sulfoxide (DMSO), add NHS/EDCI activation, and add c-RGD dimethyl sulphoxide solution in
45 DEG C are reacted 10 hours, are precipitated in acetone, are filtered to obtain white powder c-RGD-HPZ.
Case study on implementation 5
The preparation of A-B-C2-RGD three block compounds
Experimental procedure：
With case study on implementation 4.
Case study on implementation 6
Phase inversions of the HPZ to ZAISe/ZnS quantum dots
Experimental procedure：
After taking 1mL ZAISe/ZnS to be dissolved in ethanol, 4000r/min centrifugal purifications, precipitation is dissolved in CHCl3A liquid is made；Claim
After taking 1.5mg HPZ to be dissolved in dimethyl sulfoxide (DMSO), B liquid is made；Mixing reacts 5h after 55 DEG C, to the end of, add acetone/just oneself
Alkane mixing liquid precipitate, centrifuge to obtain water-soluble ZAlSe/ZnS quantum dots.
Case study on implementation 7
Phase inversions of the PPZ to ZAISe/ZnS quantum dots
Experimental procedure：
With case study on implementation 6.
Case study on implementation 8
Phase inversions of the c-RGD-HPZ to ZAISe/ZnS quantum dots
Experimental procedure：
With case study on implementation 6.
Case study on implementation 9
Phase inversions of the c-RGD-HPZ to ZCISe/ZnS quantum dots
Experimental procedure：
With case study on implementation 6.
Claims (10)
1. a kind of high molecular polymer, there is following structural formula：
Wherein a=1~15, b=1~15, n=5~33.
2. the preparation method of high molecular polymer as claimed in claim 1, using following steps：
(1) preparation of sulfobetaines：
By to N, the free-NH of N- dimethyl -1,3- propane diamine (DMPDA)2Protection, sulfuryl amine and deprotection prepare sulphur
Base glycine betaine；
(2) preparation of polymer：
With fatty amido-azacyclo- (A), HPMA (B), sulfobetaines (C) for raw material, EDC/NHS is catalyst, instead
High molecular polymer of the present invention should be made.
3. method as claimed in claim 2, it is characterised in that：In the step (1), dissociate-NH2Blocking group be two carbonic acid
Di tert butyl carbonate ((Boc)2O)。
4. method as claimed in claim 2, it is characterised in that：In the step (1), sulfuryl amine reagent is in the sulphurs of 1,3- third
Ester.
5. method as claimed in claim 2, it is characterised in that：In the step (2), fatty amido-azacyclo- (A), poly- Malaysia
Acid anhydrides (B), sulfobetaines (C) mol ratio are：1∶1∶2、1∶1∶1.
6. method as claimed in claim 2, it is characterised in that：In the step (2), reaction dissolvent is dimethyl sulfoxide (DMSO)
(DMSO), the reaction time is 5h or so, after completion of the reaction, adds small polar organic solvent recrystallization and filters to obtain macromolecule of the present invention
Polymer；The small polar organic solvent is ether, ethyl acetate or petroleum ether.
7. application of the high molecular polymer as claimed in claim 1 in oil-soluble quantum dot phase inversion.
8. application as claimed in claim 7, using following steps：
Step 1: high molecular polymer of the present invention is dissolved in dimethyl sulfoxide (DMSO) (DMSO), A liquid is made；
Step 2: after oil-soluble quaternary quantum dot is utilized into ethanol purification, it is scattered in chloroform, B liquid is made；
Step 3: A drops are entered in B liquid, after reaction forms homogeneous phase solution, acetone/n-hexane mixed solution pelleting centrifugation is added,
The precipitation of acquisition is water-soluble quantum dot.
9. application as claimed in claim 8, it is characterised in that：The temperature of the DMSO described in step 1 is 25~50 DEG C；In step
In rapid two, oil-soluble quaternary quantum dot is CuZnInSe/ZnS or AgZnInSe/ZnS；The volume of chloroform is 1~3mL.
10. application as claimed in claim 8, it is characterised in that：Reaction temperature is 45~70 DEG C in step 3；Reaction time is
5~7h；The ratio of acetone/n-hexane mixed solution is：Acetone/n-hexane (V/V)=1: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710252430.6A CN107383252A (en) | 2017-04-17 | 2017-04-17 | Polymer for quaternary quantum dot phase transfer and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710252430.6A CN107383252A (en) | 2017-04-17 | 2017-04-17 | Polymer for quaternary quantum dot phase transfer and its preparation method and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107383252A true CN107383252A (en) | 2017-11-24 |
Family
ID=60338305
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710252430.6A Pending CN107383252A (en) | 2017-04-17 | 2017-04-17 | Polymer for quaternary quantum dot phase transfer and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107383252A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110643346A (en) * | 2019-09-05 | 2020-01-03 | 深圳市华星光电半导体显示技术有限公司 | Quantum dot coordination method, quantum dot and display device |
| CN114163998A (en) * | 2021-12-15 | 2022-03-11 | 浙江工业大学 | Perovskite quantum dot/silicon dioxide composite nano probe for quickly detecting trace water in alcohol and application method thereof |
-
2017
- 2017-04-17 CN CN201710252430.6A patent/CN107383252A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| DAWEI DENG等: ""Highly Iuminescent water-soluble quaternary Zn-Ag-In-S quantum dots for tumor cell-targeted imaging"", 《PHYS.CHEM.CHEM.PHYS.》 * |
| DAWEI DENG等: ""Quaternary Zn-Ag-In-Se Quantum Dots for Biomedical Optical Imaging of RGD-Modified Micelles"", 《ACS APPL.MATER.INTERFACES》 * |
| TAO DENG等: ""Water-Solubilizing Hydrophobic ZnAgInSe/ZnS QDs with Tumor- Targeted cRGD-Sulfobetaine-PIMA-Histamine Ligands via a Self- Assembly Strategy for Bioimaging"", 《ACS APPL.MATER.INTERFACE》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110643346A (en) * | 2019-09-05 | 2020-01-03 | 深圳市华星光电半导体显示技术有限公司 | Quantum dot coordination method, quantum dot and display device |
| WO2021042458A1 (en) * | 2019-09-05 | 2021-03-11 | 深圳市华星光电半导体显示技术有限公司 | Coordination method for quantum dots, quantum dots and display apparatus |
| CN114163998A (en) * | 2021-12-15 | 2022-03-11 | 浙江工业大学 | Perovskite quantum dot/silicon dioxide composite nano probe for quickly detecting trace water in alcohol and application method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ali et al. | Red fluorescent carbon nanoparticle-based cell imaging probe | |
| Yang et al. | Biomineralization-inspired crystallization of manganese oxide on silk fibroin nanoparticles for in vivo MR/fluorescence imaging-assisted tri-modal therapy of cancer | |
| Gui et al. | Recent advances in synthetic methods and applications of photo-luminescent molecularly imprinted polymers | |
| Tasso et al. | Sulfobetaine–Vinylimidazole block copolymers: a robust quantum dot surface chemistry expanding bioimaging’s horizons | |
| CN105596294B (en) | A kind of nano target carrier micelle and preparation method thereof and a kind of anticancer drug and preparation method thereof | |
| Xu et al. | Facile preparation of pH-sensitive and self-fluorescent mesoporous silica nanoparticles modified with PAMAM dendrimers for label-free imaging and drug delivery | |
| Hu et al. | A fast synthesis of near-infrared emitting CdTe/CdSe quantum dots with small hydrodynamic diameter for in vivo imaging probes | |
| CN110128665B (en) | Amphiphilic block polymer near-infrared fluorescent probe based on azo reductase response and application | |
| CN104968712A (en) | Nested supramolecular capsules | |
| CN112409384B (en) | Double thiophene thiadiazole receptor near-infrared two-region fluorescent molecule and preparation method and application thereof | |
| Yan et al. | General and scalable approach to bright, stable, and functional AIE fluorogen colloidal nanocrystals for in vivo imaging | |
| JP6164637B2 (en) | Fluorescent probe for labeling biological samples | |
| Qiao et al. | Rapid conversion from common precursors to carbon dots in large scale: Spectral controls, optical sensing, cellular imaging and LEDs application | |
| CN101294955A (en) | Production method of probe molecule for recognizing tumor cell by specificity | |
| Tu et al. | Silicon quantum dot nanoparticles with antifouling coatings for immunostaining on live cancer cells | |
| CN107541208B (en) | Preparation method of core-shell graphene quantum dot @ mesoporous silica nanomaterial | |
| WO2017043484A1 (en) | Intracellular delivery vehicle | |
| CN106362162A (en) | ZnO@PMAA-b-PHPMA quantum dot nanomaterial and preparation thereof and application of nanomaterial serving as drug carrier | |
| CN107383252A (en) | Polymer for quaternary quantum dot phase transfer and its preparation method and application | |
| Xing et al. | Disulfide Cross‐Linked Polypeptide Nanogel Conjugated with a Fluorescent Probe as a Potential Image‐Guided Drug‐Delivery Agent | |
| CN110665014A (en) | Preparation method of rare earth MOF nanoparticles with dual-mode imaging function | |
| Zhang et al. | Organic-to-aqueous phase transfer of Zn–Cu–In–Se/ZnS quantum dots with multifunctional multidentate polymer ligands for biomedical optical imaging | |
| CN103642491B (en) | Strong signal and low toxicity composite nanometer material and preparation method thereof | |
| CN106243244B (en) | A kind of carboxyl chitosan namo fluorescence probe and preparation method thereof with aggregation-induced emission characteristic | |
| Zhao et al. | A novel strategy for the aqueous synthesis of down-/up-conversion nanocomposites for dual-modal cell imaging and drug delivery |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20171124 |