CN107189074A - The surface-functionalized method of modifying of metal-organic framework materials based on liposome membrane - Google Patents
The surface-functionalized method of modifying of metal-organic framework materials based on liposome membrane Download PDFInfo
- Publication number
- CN107189074A CN107189074A CN201710386696.XA CN201710386696A CN107189074A CN 107189074 A CN107189074 A CN 107189074A CN 201710386696 A CN201710386696 A CN 201710386696A CN 107189074 A CN107189074 A CN 107189074A
- Authority
- CN
- China
- Prior art keywords
- liposome
- metal
- mofs
- modifying
- liposomes
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
- C08G83/008—Supramolecular polymers
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to technical field of nanometer material preparation, disclose a kind of surface-functionalized method of modifying of the metal-organic framework materials based on liposome membrane, the MOFs materials and liposome being mutually matched are selected, makes the presence of Electrostatic Absorption or covalent attachment effect between liposome membrane and the exposed avtive spot of MOFs material surfaces；Corresponding MOFs materials are directly mixed with liposome solutions, fusion cladding is carried out, centrifuge washing obtains final product；Quality evaluation and Performance Evaluation are carried out to final product, by Electrostatic Absorption or covalent attachment, liposome realizes the cladding to MOFs materials, completes the surface-functionalized modification to MOFs materials.Higher biological stability can be provided compared to traditional polyethyleneglycol modified method；It is easy to operate, and modification efficiency is also of a relatively high；Organic solvent or other toxic reagents need not be used；It is expected to assign MOFs materials new function when in terms of applied to medicine delivery, molecular image.
Description
Technical field
The invention belongs to technical field of nanometer material preparation, more particularly to a kind of metal organic framework based on liposome membrane
The surface-functionalized method of modifying of material.
Background technology
Metal-organic framework materials (Metal-organic frameworks, MOFs) be using inorganic metal ion cluster as with
Position node, using organic ligand as connection unit, a kind of three-dimensional poroid material formed by coordination.Due to various
Structure composition, higher specific surface area, adjustable pore size, the spy such as regulatable appearance and size and good biocompatibility
Point, MOFs materials are widely used in the biomedical sectors such as medicine delivery, molecular imaging, bio-sensing.From the organic bone of metal
From the point of view of the design feature of frame material, there is the metal ion binding site not being coordinated and not connected organic ligand connection in its surface
Node, therefore must carry out functional modification to its surface to improve its biological stability and life when carrying out biomedical applications
Thing security.Traditional surface-functionalized method of modifying such as connects polyethylene glycol in MOFs material surfaces, although to a certain degree
On can improve the biological stability and biological safety of MOFs materials, but still MOFs materials can not be met applied to biology
To the demand of biological stability during medical domain, while can not also improve MOFs materials is delivering some imaging molecules or curative
The present situation of early release occurs during thing, therefore, in the urgent need to developing a kind of new, modification means that functionalization is stronger, not only
The biological stability of MOFs materials can be significantly improved, moreover it is possible to which basis assigns MOFs materials some new functions herein, for example in fact
Controlled release of existing delivery molecule etc..
In summary, the problem of prior art is present be：There is application in traditional MOFs functionalizing material surfaces method of modifying
It is poor to biological stability when biomedical sector, it is impossible to improve MOFs materials and occur when delivering imaging molecule or medicine
Early release.
The content of the invention
The problem of existing for prior art, the invention provides a kind of metal-organic framework materials based on liposome membrane
Surface-functionalized method of modifying.
The present invention is achieved in that a kind of surface-functionalized modification of the metal-organic framework materials based on liposome membrane
Method, it is autonomous that the surface-functionalized method of modifying of the metal-organic framework materials based on liposome membrane passes through liposome membrane
The mode of fusion is coated to MOFs material surfaces；
The surface-functionalized method of modifying of the metal-organic framework materials based on liposome membrane is specifically included：
(1) the MOFs materials and liposome being mutually matched are selected, makes liposome membrane and the exposed activity of MOFs material surfaces
There is Electrostatic Absorption or covalent attachment effect between site；
(2) corresponding MOFs materials are directly mixed with liposome solutions, carries out fusion cladding, centrifuge washing is obtained finally
Product；
(3) quality evaluation and Performance Evaluation are carried out, it is determined that by Electrostatic Absorption or covalent attachment, liposome is successfully realized pair
The cladding of MOFs materials, completes the surface-functionalized modification to MOFs materials.
Further, the MOFs materials include UiO series, MIL series and ZIF series；
The UiO series includes UiO-66, UiO-66-NH2；
The MIL series includes MIL-100, MIL-101-NH2、MIL-88A、MIL-53；
The ZIF series includes ZIF-8, ZIF-7, ZIF-11, ZIF-5.
Further, the liposome includes anionic liposome, neutral liposome, cationic-liposome；
The anionic liposome is DOPA liposomes, DPPA liposomes, DOPG liposomes, DOPS liposomes；
The neutral liposome is DOPC liposomes, DPPC liposomes；
The cationic-liposome is DOTAP liposomes.
Further, the synthesis material of the liposome includes 1,2- DOPCs DOPC, 1,2- dioleoyl phospholipid
Sour DOPA, 2- dioleoyl hydroxypropyl -3-N, N, N- trimethylammonium chlorine DOTAP, dioleoyl phosphatidylserine DOPS, dioleoyl
Phosphatidyl glycerol DOPG, DOPE-polyethylene glycol 18:1PEG-2000PE, cholesterol chol.
Further, the synthetic method of the MOFs materials comprises the following steps：
(1) UiO series and ZIF series are synthesized with solvent-thermal process method, weighs metal ion with organic ligand that it is ultrasonic
It is dispersed in corresponding solvent, adds to be transferred to after conditioning agent in water heating kettle and react, the ultrasonic redisperse of centrifugation washs several with solvent
It is secondary to obtain final product；
(2) MIL series is synthesized with microwave process for synthesizing, weighs metal ion and organic ligand by its ultrasonic disperse corresponding
In solvent, it is transferred in microwave reaction bottle, is reacted on microwave synthesizer, the ultrasonic redisperse of rotating speed centrifugation is washed with solvent
Wash and obtain final product several times.
Further, metal ion is anhydrous zirconium chloride when synthesizing UiO-66, and the amount weighed is 10~30mg；Organic ligand is
Terephthalic acid (TPA), the amount weighed is 30~80mg；Reaction dissolvent is DMF, and the amount measured is 3~6mL；Adjust
Section agent is glacial acetic acid, and the amount measured is 0.2~1mL；Reaction temperature is 60~110 DEG C；Reaction time is 10~24h；Centrifuged
Journey rotating speed is 10000rpm, and the time is 10min, and washing reagent is DMF and absolute ethyl alcohol, and washing times are 2
~5 times；
Metal ion is zinc nitrate hexahydrate when synthesizing ZIF-8, and the amount weighed is 1.0~3.5g；Organic ligand is diformazan
Base imidazoles, the amount weighed is 4.3~7.2g；Reaction dissolvent is methanol, and the amount measured is 50~200mL；Reaction temperature be 15~
60℃；Reaction time is 0.5~12h；Centrifugal process rotating speed is 12000rpm, and the time is 15min, and washing reagent is methanol and nothing
Water-ethanol, washing times are 2~5 times.
Further, metal ion is Iron(III) chloride hexahydrate when synthesizing MIL-100, and the amount weighed is 1.0~3.5g；It is organic
Part is trimesic acid, and the amount weighed is 4.3~7.2g；Reaction dissolvent is the mixed solution of water and ethanol, and the amount measured is
50~200mL；Reaction temperature is 15~60 DEG C；Reaction time is 0.5~12h；Centrifugal process rotating speed is 12000rpm, and the time is
15min, washing reagent is methanol and absolute ethyl alcohol, and washing times are 2~5 times；
Synthesize MIL-101-NH2When metal ion be Iron(III) chloride hexahydrate, the amount weighed be 1.0~3.5g；It is organic to match somebody with somebody
Body is adjacent amino terephthalic acid (TPA), and the amount weighed is 4.3~7.2g；Reaction dissolvent is that the amount measured is 50~200mL；Reaction
Temperature is 15~60 DEG C；Reaction time is 0.5~12h；Centrifugal process rotating speed is 12000rpm, and the time is 15min, washing reagent
For methanol and absolute ethyl alcohol, washing times are 2~5 times.
Further, the synthetic method of the liposome is specifically included：
Liposome is prepared with extruder extrusion molding, various 2.5~10mg of lipid is weighed by quality proportioning, is dissolved in 2~4mL chlorine
In the mixed solution of imitative and methanol, volume ratio is 4:1, dissolving in a water bath will be organic with Rotary Evaporators after being mixed thoroughly
Solvent is drained, and is dried in vacuum overnight at room temperature；4~6ml HEPES buffer solution room temperature 1~2h of aquation are added, then by lipid
Body extruder is extruded 21 times, obtains final liposome.
Further, quality proportioning is DOPA during the synthesis DOPA liposomes:chol：18:1PEG-2000PE=15:6:
1, bath temperature is 35 DEG C；
The quality proportioning of lipid is DOPC when synthesizing DOPC liposomes:chol：18:1PEG-2000PE=15:6:1, water-bath
Temperature is 25 DEG C；
The quality proportioning of lipid is DOPA when synthesizing DOTAP liposomes:chol：18:1PEG-2000PE=15:6:1, water
Bath temperature is 40 DEG C.
Another object of the present invention is to provide a kind of table by the metal-organic framework materials based on liposome membrane
The metal-organic framework materials of face functional modification method modification.
Advantages of the present invention and good effect are：Select powered property different, the different liposome difference of water-wet side group
Probe into and merge situation with the autonomous of MOFs materials, find to utilize the Electrostatic Absorption between liposome membrane and MOFs material surfaces or covalent
Lipid bilayer can be achieved in the autonomous fusion of MOFs material surfaces, the table for making it successfully be coated on MOFs materials in connection
Face so that the MOFs materials after modification have the biological stability of superelevation.Liposome as a comprehensive transport agent
It is widely used in image-forming contrast medium, small-molecule drug, biomolecule (including oligonucleotides, polypeptide, albumen and gas point
Son) transport and delivering.Liposome is mainly made up of phospholipid bilayer, similar with the composition of cell membrane, therefore with higher
Biological stability and biological safety.Compared with traditional MOFs material surface method of modifying, it is preferable using biocompatibility
Liposome membrane to MOFs surfaces carry out cladding be a kind of novel surface-functionalized modification means, before good application
Scape.
Liposome can be achieved by the Electrostatic Absorption between liposome membrane and MOFs material surfaces or covalent attachment in the present invention
Autonomous fusion and cladding of the film in MOFs material surfaces, complete the surface-functionalized modification to MOFs materials.The invention is constructed
A kind of new method simple to operate, green high-efficient that surface-functionalized modification is carried out for MOFs materials, is the table of MOFs materials
Face functional modification provides a kind of new thinking；Also assigned while MOFs materials biological stability is improved with biological safety
Some new functions of MOFs materials have been given, the common delivering, the controlled release of delivery molecule such as hydrophilic and hydrophobic drug molecule,
It is significant to its application in terms of biomedical sector.In addition the combination also for MOFs materials and liposome is carried
A new example is supplied, the MOFs materials for completing surface modification using liposome membrane will be expected to while possessing the excellent of two kinds of materials
More property, has greatly widened MOFs materials and application prospect of the liposome in terms of biomedical sector.
It is provided by the present invention carry out the method for surface-functionalized modification mainly with Electrostatic Absorption for MOFs materials or
Covalent effect, to realize autonomous fusion of the liposome membrane in MOFs material surfaces, completes the table to MOFs materials as driving force
Face functional modification, is not disclosed in current periodical and paper.Can compared to traditional polyethyleneglycol modified method
To provide higher biological stability；It is easy to operate, directly mixed with liposome only by MOFs materials just can a step realize, and
Modify efficiency also of a relatively high；Organic solvent or other toxic reagents need not be used, meet the theory of green syt；By lipid
Body is organically combined together with MOFs materials, is expected to assign MOFs materials when in terms of applied to medicine delivery, molecular image
The new function of material.
Brief description of the drawings
Fig. 1 is the surface-functionalized modification of the metal-organic framework materials provided in an embodiment of the present invention based on liposome membrane
Method flow diagram.
Fig. 2 be the DOPA liposomes prepared in embodiment 1 provided in an embodiment of the present invention hydration kinetics dimensional drawing with
Potential diagram；
In figure：(a) the hydration kinetics dimensional drawing of DOPA liposomes；(b) it is the potential diagram of DOPA liposomes.
Fig. 3 is the UiO-66 prepared in embodiment 2 provided in an embodiment of the present invention stereoscan photograph and transmission electron microscope
Photo schematic diagram；
In figure：(a) stereoscan photograph for the UiO-66 for being a diameter of 230nm of hydration kinetics；(b) it is hydration kinetics
A diameter of 150nm UiO-66 transmission electron microscope photo.
Fig. 4 be the UiO-66@DOPA prepared in embodiment 3 provided in an embodiment of the present invention hydration kinetics dimensional drawing with
Potential diagram；
In figure：(a) UiO-66@DOPA hydration kinetics dimensional drawing；(b) potential diagram for being UiO-66@DOPA.
Fig. 5 is DOPA liposomes, UiO-66, UiO-66@DOPA infrared figure in embodiment provided in an embodiment of the present invention
Compose schematic diagram；
Wherein 1 is the infared spectrum of DOPA liposomes；2 be UiO-66 infared spectrum；3 be the infrared of UiO-66@DOPA
Collection of illustrative plates.
Fig. 6 be in embodiment 6 provided in an embodiment of the present invention UiO-66-PEG and UiO-66@DOPA in PBS
Stability change figure.
Embodiment
In order to make the purpose , technical scheme and advantage of the present invention be clearer, with reference to embodiments, to the present invention
It is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to
Limit the present invention.
The intrinsic design feature of MOFs materials determines that its surface certainly exists many exposed avtive spots, i.e., be not coordinated
Metal ion binding site and not connected organic ligand connection unit, with good surface modification basis.Liposome membrane
The exposed group of surfaces externally and internally has diversity and alternative.By reasonably select the species of MOFs materials and liposome come
Matched, will using liposome membrane and interaction such as Van der Waals force, electrostatic interaction or the covalent effect of MOFs material surfaces
Effective cladding of the liposome membrane on MOFs material surfaces is realized, the biological stability of MOFs materials is greatly enhanced.
The application principle of the present invention is explained in detail below in conjunction with the accompanying drawings.
As shown in figure 1, the function of surface of the metal-organic framework materials provided in an embodiment of the present invention based on liposome membrane
Change method of modifying to comprise the following steps：
S101：0.1~2.0mg MOFs materials are weighed, ultrasonic disperse is dense in 1~4ml corresponding liposome solutions
Spend for 2.5mg/mL, 0.5~2h is stood at room temperature, carrying out piping and druming with liquid-transfering gun every 5~15min is mixed several times, and reaction is tied
It is washed with deionized after beam three times, washes away the uncoated liposome in MOFs material surfaces, finally gives one layer of Surface coating
The MOFs materials of lipid bilayer, i.e. MOFs@liposome；
S102：The surface of MOFs materials is successfully coated on using liposome, MOFs materials after surface-functionalized modification are completed
Compared to unmodified preceding MOFs materials because liposome membrane is relatively thin, about 5~10nm, hydrodynamics size is basically unchanged, table
The current potential of face current potential and the liposome of selected cladding is essentially identical.
The MOFs materials of the present invention include UiO series, MIL series and ZIF series etc..
Wherein UiO series is including UiO-66, UiO-66-NH2 etc.；MIL series include MIL-100, MIL-101-NH2,
MIL-88A, MIL-53 etc.；ZIF series is including ZIF-8, ZIF-7, ZIF-11, ZIF-5 etc..
The liposome of the present invention includes anionic liposome such as DOPA liposomes, DPPA liposomes, DOPG liposomes, DOPS
Liposome etc.；Neutral liposome such as DOPC liposomes, DPPC liposomes etc.；Cationic-liposome such as DOTAP liposomes etc..
The synthesis material of liposome includes 1,2- DOPCs (DOPC), and 1,2- dioleoyl phospholipid is sour (DOPA),
2- dioleoyl hydroxypropyl -3-N, N, N- trimethylammonium chlorine (DOTAP), dioleoyl phosphatidylserine (DOPS), dioleoyl phosphorus
Phosphatidyl glycerol (DOPG), DOPE-polyethylene glycol (18:1PEG-2000PE), cholesterol (chol)
MOFs material prioritizing selections UiO-66, MIL-100, MIL-101-NH2.
Liposome prioritizing selection DOPA liposomes, DOTAP liposomes, DOPC liposomes.
The synthetic method of MOFs materials of the present invention is specifically included：
(1) with solvent-thermal process method synthesis UiO series and ZIF series, concretely comprise the following steps weigh appropriate metal ion with
Its ultrasonic disperse in corresponding solvent, is transferred in water heating kettle, in a constant temperature by organic ligand after adding appropriate conditioning agent
Degree lower reaction a period of time, with certain ultrasonic redisperse of rotating speed centrifugation, washed with suitable solvent and obtain final product several times.
Metal ion is anhydrous zirconium chloride when UiO-66 is synthesized in above-mentioned steps, and the amount weighed is 10~30mg, specifically may be used
For 25mg；Organic ligand is terephthalic acid (TPA), and the amount weighed is 30~80mg, concretely 40mg；Reaction dissolvent is N, N- bis-
NMF, the amount measured is 3~6mL, concretely 4mL；Conditioning agent is glacial acetic acid, and the amount measured is 0.2~1mL, tool
Body can be 0.5mL；Reaction temperature is 60~110 DEG C, concretely 80 DEG C；Reaction time is 10~24h, concretely 15h；From
Heart process rotating speed is 10000rpm, and the time is 10min, and washing reagent is DMF and absolute ethyl alcohol, washing time
Number is 2~5 times, concretely 3 times.
Metal ion is zinc nitrate hexahydrate when synthesizing ZIF-8, and the amount weighed is 1.0~3.5g, concretely 2.0g；Have
Machine part is methylimidazole, and the amount weighed is 4.3~7.2g, concretely 5.6g；Reaction dissolvent is methanol, and the amount measured is
50~200mL, concretely 130mL；Reaction temperature is 15~60 DEG C, concretely 25 DEG C；Reaction time is 0.5~12h, tool
Body can be 1h；Centrifugal process rotating speed is 12000rpm, and the time is 15min, and washing reagent is methanol and absolute ethyl alcohol, washing times
For 2~5 times, concretely 3 times.
(2) synthesize MIL series with microwave process for synthesizing, concretely comprise the following steps weigh appropriate metal ion and organic ligand by its
Ultrasonic disperse is transferred them in microwave reaction bottle in corresponding solvent, and corresponding reaction bar is set on microwave synthesizer
Part is reacted, and with certain ultrasonic redisperse of rotating speed centrifugation, is washed with suitable solvent and is obtained final product several times.
Metal ion is Iron(III) chloride hexahydrate when synthesizing MIL-100, and the amount weighed is 1.0~3.5g, concretely
2.0g；Organic ligand is trimesic acid, and the amount weighed is 4.3~7.2g, concretely 5.6g；Reaction dissolvent is water and ethanol
Mixed solution, the amount measured is 50~200mL, concretely 130mL；Reaction temperature is 15~60 DEG C, concretely 25 DEG C；
Reaction time is 0.5~12h, concretely 1h；Centrifugal process rotating speed is 12000rpm, and the time is 15min, and washing reagent is first
Alcohol and absolute ethyl alcohol, washing times are 2~5 times, concretely 3 times.
Synthesize MIL-101-NH2When metal ion be Iron(III) chloride hexahydrate, the amount weighed be 1.0~3.5g, specifically may be used
For 2.0g；Organic ligand is adjacent amino terephthalic acid (TPA), and the amount weighed is 4.3~7.2g, concretely 5.6g；Reaction dissolvent
For the amount measured is 50~200mL, concretely 130mL；Reaction temperature is 15~60 DEG C, concretely 25 DEG C；Reaction time
For 0.5~12h, concretely 1h；Centrifugal process rotating speed is 12000rpm, and the time is 15min, washing reagent be methanol with it is anhydrous
Ethanol, washing times are 2~5 times, concretely 3 times.
The synthetic method of invented liposomes is specifically included：
Liposome is prepared with extruder extrusion molding, concrete implementation process is to weigh various lipids by certain quality proportioning
In 2.5~10mg, the mixed solution for being dissolved in 2~4mL chloroforms and methanol, volume ratio is 4:1, dissolve after being mixed thoroughly one
Organic solvent is drained with Rotary Evaporators under fixed bath temperature, is dried in vacuum overnight at room temperature.Add 4~6ml HEPES
Buffer solution (100mM NaCl, 10Mm HEPES, pH7.4) room temperature 1~2h of aquation, then extrudes 21 by liposome extruder
It is secondary, obtain final liposome.
Quality proportioning is DOPA when synthesizing DOPA liposomes:chol：18:1PEG-2000PE=15:6:1, bath temperature is
35℃。
The quality proportioning of lipid is DOPC when synthesizing DOPC liposomes:chol：18:1PEG-2000PE=15:6:1, water-bath
Temperature is 25 DEG C.
The quality proportioning of lipid is DOPA when synthesizing DOTAP liposomes:chol：18:1PEG-2000PE=15:6:1, water
Bath temperature is 40 DEG C.
The synthetic method of invented liposomes cladding MOFs materials is specifically included：
0.1~2.0mg MOFs materials are weighed, ultrasonic disperse is in 1~4ml corresponding liposome solutions, and concentration is
2.5mg/mL, stands 0.5~2h at room temperature, and piping and druming is carried out with liquid-transfering gun every 5~15min mixes several times, after reaction terminates
It is washed with deionized three times, washes away the uncoated liposome in MOFs material surfaces, finally gives one layer of lipid of Surface coating
The MOFs materials of bilayer, i.e. MOFs@liposome.
UiO-66 is when being UiO-66@DOPA for above method synthesis DOPA claddings, the UiO-66 weighed amount for 0.1~
0.5mg, concretely 0.3mg, the amount of DOPA liposomes is 1ml, and the driving force of wherein UiO-66@DOPA formation is UiO-66 tables
The covalent effect of the exposed zirconium ion in face and the phosphate group on DOPA liposome membranes.
When synthesis DOTAP claddings MIL-100 is MIL-100@DOPA, the amount on MIL-100 weighed is 0.5~2.0mg,
Concretely 1mg, the amount of DOTAP liposomes is 1mL, and the driving force of wherein MIL-100@DOTAP formation is naked for MIL-100 surfaces
The electrostatic interaction of the carboxylate radical of dew and the choline group on DOTAP liposome membranes.
The final surface that MOFs materials are successfully coated on using liposome, completes MOFs material phases after surface-functionalized modification
Than in unmodified preceding MOFs materials, because liposome membrane is relatively thin, about 5~10nm, hydrodynamics size is basically unchanged, surface
The current potential of current potential and the liposome of selected cladding is essentially identical, and Biostatic performance has obtained larger lifting.
The application principle of the present invention is further described with reference to specific embodiment.
Embodiment 1
The preparation of liposome
The preparation of DOPA liposomes
5mg lipids are weighed, wherein the mass ratio of various lipid compositions is DOPA/chol/18:1PEG-2000PE=15:6:
1, it is dissolved in the mixed solution of 2mL chloroforms and methanol that (volume ratio is 4:1) in 35 DEG C of water bath conditions after, dissolving is mixed thoroughly
It is lower to be drained organic solvent with Rotary Evaporators, it is dried in vacuum overnight at room temperature.Add 4ml HEPES buffer solutions (100mM
NaCl, 10Mm HEPES, pH 7.4) room temperature 1~2h of aquation, is then extruded 21 times, obtaining size is by liposome extruder
120~130nm DOPA liposomes.Such as Fig. 2 (a) show the hydration kinetics diameter figure of DOPA liposomes, such as Fig. 2 (b) institutes
It is shown as the potential diagram of DOPA liposomes.
The preparation of DOPC liposomes
5mg lipids are weighed, wherein the mass ratio of various lipid compositions is DOPC/chol/18:1PEG-2000PE=15:6:
1, it is dissolved in the mixed solution of 2mL chloroforms and methanol that (volume ratio is 4:1) in 25 DEG C of water bath conditions after, dissolving is mixed thoroughly
It is lower to be drained organic solvent with Rotary Evaporators, it is dried in vacuum overnight at room temperature.Add 4ml HEPES buffer solutions (100mM
NaCl, 10Mm HEPES, pH 7.4) room temperature 1~2h of aquation, then extrudes 21 times by liposome extruder, obtains hydrodynamic force
Learn the DOPC liposomes that size is 120~130nm.
The preparation of DOTAP liposomes
5mg lipids are weighed, wherein the mass ratio of various lipid compositions is DOTAP/chol/18:1PEG-2000PE=15:
6:1, it is dissolved in the mixed solution of 2mL chloroforms and methanol (volume ratio is 4/1), dissolves after being mixed thoroughly in 40 DEG C of water-bath bars
Organic solvent is drained with Rotary Evaporators under part, is dried in vacuum overnight at room temperature.Add 4ml HEPES buffer solutions (100mM
NaCl, 10Mm HEPES, pH 7.4) room temperature 1~2h of aquation, then extrudes 21 times by liposome extruder, obtains hydrodynamic force
Learn the DOTAP liposomes that size is 120~130nm.
Embodiment 2
The preparation of MOFs materials
UiO-66 preparation
Weigh 15.5mg zirconium chlorides (ZrCl4), 50mg terephthalic acid (TPA)s (H2BDC), it is dissolved in 4ml DMFs
(DMF) in, dissolving is complete, adds 0.3~0.9ml acetic acid, is transferred to hydrothermal reaction kettle, 18h is reacted at 90~100 DEG C,
Obtained solution centrifuges 10min under 10000rpm rotating speeds, is washed twice, obtained respectively with ethanol and water by ultrasonic disperse and centrifugation
To UiO-66, its hydrodynamics size is 140~900nm.As Fig. 3 (a) show a diameter of 230nm of hydrodynamics UiO-66
Scanning electron microscope (SEM) photograph, such as Fig. 3 (b) show a diameter of 150nm of hydrodynamics UiO-66 transmission electron microscope picture.
MIL-100 preparation
Weigh 486mg ferric chloride hexahydrate (FeCl3·6H2O), 140mg equal phthalic acid (H3BTC), it is dissolved in 5ml
In the mixed solution of water and ethanol, the volume ratio of its reclaimed water and ethanol is 1:0.25~4, dissolving is complete, is transferred to the micro- of 10ml
In ripple reaction bulb, 130 DEG C of reaction 5min in microwave synthesizer, obtained solution centrifuges 20min under 10500rpm rotating speeds, led to
Cross ultrasonic disperse to be washed with ethanol three times with centrifugation, obtain MIL-100, hydrodynamics size is 150~500nm.
MIL-101-NH2Preparation
Weigh 27mg ferric chloride hexahydrate (FeCl3·H2O), 18.1mg adjacent amino terephthalic acid (TPA) (H2BDC-
NH2), in the mixed solution for being dissolved in 5ml water and ethanol, the volume ratio of its reclaimed water and ethanol is 1:0.25~4, dissolving is complete, turns
In the microwave reaction bottle for moving to 10ml, 60 DEG C of reaction 5min in microwave synthesizer, obtained solution is under 10500rpm rotating speeds
10min is centrifuged, is washed by ultrasonic disperse and centrifugation with ethanol three times, obtains MIL-101-NH2, hydrodynamics size be 170~
500nm。
ZIF-8 preparation
Weigh 2.4g six water and zinc nitrate (Zn (NO3)2·6H2O), 5.28g methylimidazole (2-MIm), is dissolved in
In 100ml methanol, dissolving is complete, is transferred in 250ml round-bottomed flask and carries out magnetic agitation, react 30 at room temperature~
90min, obtained solution centrifuges 1.5h under 7800rpm rotating speeds, is washed three times, obtained with methanol by ultrasonic disperse and centrifugation
ZIF-8, hydrodynamics size is 100~300nm.
ZIF-7
Weigh the water of 136mg six and zinc nitrate (Zn (NO3)2·6H2O), 120mg benzimidazoles (bIm), is dissolved in 5mlN, N- bis-
In NMF (DMF), dissolving is complete, is transferred in 25ml round-bottomed flask and carries out magnetic agitation, 10 are reacted at room temperature
~30min, obtained solution centrifuges 1.5h under 7800rpm rotating speeds, is washed respectively with DMF with methanol with centrifugation by ultrasonic disperse
Three times, ZIF~7 are obtained, hydrodynamics size is 300~600nm.
Embodiment 3
DOPA liposomes are covalently attached cladding UiO-66
DOPA lipid water-wet sides end is phosphate group, can be combined with the zirconium ion not being coordinated of UiO-66 surface exposures
Site is covalently attached, and DOPA liposomes is independently merged on UiO-66 surface, so as to complete the cladding to UiO-66, is remembered
For UiO-66@DOPA, the DOPA fat that it is 1mg/mL in 1mL concentration by 1mg UiO-66 ultrasonic disperses that concrete implementation process, which is,
In plastid solution, stand 1h at room temperature, each 10min carries out piping and druming with liquid-transfering gun and mixed several times, reaction spent after terminating from
Sub- water washing three times, washes away the uncoated DOPA liposomes on UiO-66 surfaces, finally gives one layer of DOPA lipid of Surface coating
The UiO-66 of double layerings, i.e. UiO-66@DOPA.As Fig. 4 (a) show UiO-66@DOPA hydrodynamics diameter figure, such as Fig. 4
(b) show UiO-66@DOPA potential diagram, in order to further prove UiO-66@DOPA successful structure, to UiO-66,
DOPA liposomes, UiO-66@DOPA carry out the measure of infared spectrum respectively, as shown in figure 5, measurement result shows UiO-66@
DOPA possesses UiO-66 and the distinctive functional group of DOPA liposomes simultaneously, it was demonstrated that DOPA liposomes are successfully coated on UiO-66 table
Face.
Embodiment 4
DOPC liposomes Electrostatic Absorption coats MIL-100
DOPC lipid water-wet sides end is phosphate group and choline group, although being that final powered property is neutrality,
The choline group of its hydrophobic side end positively charged still can be with MIL-100 surface exposures not connected carboxylic acid ion be connected
Site carries out Electrostatic Absorption, DOPC liposomes is independently merged on MIL-100 surface, so that the cladding to MIL-100 is completed,
It is designated as MIL-100@DOPC, it by 0.5mg MIL-100 ultrasonic disperses in 1mL concentration is 1mg/mL's that concrete implementation process, which is,
In DOPC liposome solutions, 1h is stood at room temperature, each 10min carries out piping and druming with liquid-transfering gun and mixed several times, after reaction terminates
It is washed with deionized three times, washes away the uncoated DOPC liposomes on MIL-100 surfaces, finally give one layer of Surface coating
The MIL-100, i.e. MIL-100@DOPC of the double layerings of DOPC lipids.
Embodiment 5
UiO-66-PEG preparation
NH2- PEG can be connected by covalent effect with the carboxylate radical connection site of UiO-66 surface exposures, and be used
EDC/NHS, which carries out activation, can improve reaction efficiency, and concrete implementation process is the UiO-66 for weighing 0.5mg, by its ultrasound point
It is dispersed in 1mL NH2In-PEG-5000DMF solution, wherein NH2- PEG-5000DMF solution concentrations are 3~5mg/mL, are added
5mg NHS and 1mg EDC, be vortexed concussion 12h, 10000rpm centrifugation 10min under conditions of 25 DEG C, passes through centrifuge-redisperse
Mode be washed with deionized 3 times, wash away unreacted NH2-PEG, EDC, NHS, finally give the upper PEG's of surface connection
UiO-66, i.e. UiO-66-PEG.
Embodiment 6
UiO-66-PEG and UiO-66@DOPA biological stability is determined
Simulate physiological environment in vitro using PBS and 10% hyclone culture medium, according to UiO-66-PEG with
The change of UiO-66@DOPA-liposome hydrodynamics diameter dimensions under the conditions of corresponding to its biological stability come to entering
Row is determined.Four groups are set to be measured respectively, concrete implementation process is as follows：
Group 1 is UiO-66-PEG Stability Determinations in PBS：Take 0.5mg UiO-66-PEG ultrasonic disperses extremely
In 5ml PBS, it is placed in 37 DEG C of water-baths, enters water-filling in 0h, 0.5h, 1h, 2h, 4h, 8h, 16h, 32h, 48h respectively
The measure of aerodynamic size.
Group 2 is UiO-66-PEG Stability Determinations in 10% hyclone culture medium：0.5mg UiO-66-PEG is taken to surpass
Sound is dispersed in 5ml 10% hyclone culture medium, is placed in 37 DEG C of water-baths, respectively 0h, 0.5h, 1h, 2h, 4h, 8h,
The measure of hydrodynamics size is carried out when 16h, 32h, 48h.
Group 3 is UiO-66@DOPA Stability Determinations in PBS：Take 0.5mg UiO-66@DOPA ultrasonic disperses
Into 5ml PBS, it is placed in 37 DEG C of water-baths, is carried out respectively in 0h, 0.5h, 1h, 2h, 4h, 8h, 16h, 32h, 48h
The measure of hydrodynamics size.
Group 4 is UiO-66@DOPA Stability Determinations in 10% hyclone culture medium：Take 0.5mg UiO-66-PEG
Ultrasonic disperse is placed in 37 DEG C of water-baths into 5ml 10% hyclone culture medium, respectively 0h, 0.5h, 1h, 2h, 4h, 8h,
The measure of hydrodynamics size is carried out when 16h, 32h, 48h.As a result show UiO-66@DOPA in PBS and 10% tire ox
Stability in blood serum medium is better than UiO-66-PEG, stability test result such as Fig. 6 institutes in PBS
Show.
Embodiment 7
MIL-100@DOPC are used for the common delivering of hydrophobe medicine
Because MIL-100 is more likely to deliver hydrophilic medicament, therefore it can not realize with the hydrophilic of Therapeutic Results of Combination Chemotherapy
Property medicine gemcitabine and hydrophobic drug taxol common delivery.MIL-100@DOPC can then pass through the fat on its surface
Taxol is inserted in matter bilayer to realize the common delivering of chemotherapeutics gemcitabine and taxol.Concrete implementation process
To comprise the following steps：
(1) DOPC liposomal deliveries taxol：By 1~5mg taxol and 5~10mg lipid common distribution in 4mL
In the mixed solution of chloroform and methanol, wherein the mass ratio of various lipid compositions is DOPC:chol：PE~PEG2000=15:6:
1, the volume ratio of chloroform and methanol is 4:Organic solvent used in 1,25 DEG C of water-bath revolving removing, room temperature in vacuo is dried to be added after 12h
Enter 4mLHEPES buffer solutions, 1~2h of aquation is obtained with extruding 21 times equipped with the extruder that aperture is 100nm extruded films.
(2) MIL-100 delivers gemcitabine：By 1mg MIL-100 ultrasonic disperses in the Ji Xi that 1mL concentration is 2mg/mL
In his waterfront solution, 12h is slowly stirred at a room temperature, reaction is washed with deionized three times after terminating, washes away and be not loaded with
Gemcitabine in MIL-100 cavitys, finally gives the MIL-100 for carrying gemcitabine.
By the MIL-100 ultrasonic disperses of 1mg loading gemcitabine in delivered taxol of the 1mL concentration for 1mg/mL
In DOPC liposome solutions, 1h is stood at room temperature, each 10min carries out piping and druming with liquid-transfering gun and mixed several times, after reaction terminates
It is washed with deionized three times, washes away the uncoated DOPC liposomes on MIL-100 surfaces, finally gives and delivered with joint
The gemcitabine of chemotherapy effect and the MIL-100@DOPC of taxol.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
Any modifications, equivalent substitutions and improvements made within refreshing and principle etc., should be included in the scope of the protection.
Claims (10)
1. a kind of surface-functionalized method of modifying of the metal-organic framework materials based on liposome membrane, it is characterised in that described
The surface-functionalized method of modifying of metal-organic framework materials based on liposome membrane makes liposome membrane pass through the side independently merged
Formula is coated to MOFs material surfaces；
The surface-functionalized method of modifying of the metal-organic framework materials based on liposome membrane is specifically included：
(1) the MOFs materials and liposome being mutually matched are selected, makes liposome membrane and the exposed avtive spot of MOFs material surfaces
Between exist Electrostatic Absorption or covalent attachment effect；
(2) corresponding MOFs materials are directly mixed with liposome solutions, carries out fusion cladding, centrifuge washing is finally produced
Thing；
(3) quality evaluation and Performance Evaluation are carried out, it is determined that by Electrostatic Absorption or covalent attachment, liposome is successfully realized to MOFs
The cladding of material, completes the surface-functionalized modification to MOFs materials.
2. the surface-functionalized method of modifying of the metal-organic framework materials as claimed in claim 1 based on liposome membrane, its
It is characterised by, the MOFs materials include UiO series, MIL series and ZIF series；
The UiO series includes UiO-66, UiO-66-NH2；
The MIL series includes MIL-100, MIL-101-NH2、MIL-88A、MIL-53；
The ZIF series includes ZIF-8, ZIF-7, ZIF-11, ZIF-5.
3. the surface-functionalized method of modifying of the metal-organic framework materials as claimed in claim 1 based on liposome membrane, its
It is characterised by, the liposome includes anionic liposome, neutral liposome, cationic-liposome；
The anionic liposome is DOPA liposomes, DPPA liposomes, DOPG liposomes, DOPS liposomes；
The neutral liposome is DOPC liposomes, DPPC liposomes；
The cationic-liposome is DOTAP liposomes.
4. the surface-functionalized method of modifying of the metal-organic framework materials as claimed in claim 1 based on liposome membrane, its
It is characterised by, the synthesis material of the liposome includes 1,2- DOPCs DOPC, 1,2- dioleoyl phospholipid acid DOPA,
2- dioleoyl hydroxypropyl -3-N, N, N- trimethylammonium chlorine DOTAP, dioleoyl phosphatidylserine DOPS, dioleoyl phospholipid acyl
Glycerine DOPG, DOPE-polyethylene glycol 18:1PEG-2000PE, cholesterol chol.
5. the surface-functionalized method of modifying of the metal-organic framework materials as claimed in claim 1 based on liposome membrane, its
It is characterised by, the synthetic method of the MOFs materials comprises the following steps：
(1) solvent-thermal process method synthesis UiO series and ZIF series are used, metal ion and organic ligand is weighed by its ultrasonic disperse
In corresponding solvent, add to be transferred to after conditioning agent in water heating kettle and react, the ultrasonic redisperse of centrifugation is washed with solvent and obtained several times
To final product；
(2) MIL series is synthesized with microwave process for synthesizing, weighs metal ion and organic ligand by its ultrasonic disperse in corresponding solvent
In, it is transferred in microwave reaction bottle, is reacted on microwave synthesizer, the ultrasonic redisperse of centrifugation is washed with solvent and obtained several times
To final product.
6. the surface-functionalized method of modifying of the metal-organic framework materials as claimed in claim 5 based on liposome membrane, its
It is characterised by, metal ion is anhydrous zirconium chloride during synthesis UiO-66, the amount weighed is 10~30mg；Organic ligand is to benzene two
Formic acid, the amount weighed is 30~80mg；Reaction dissolvent is DMF, and the amount measured is 3~6mL；Conditioning agent is
Glacial acetic acid, the amount measured is 0.2~1mL；Reaction temperature is 60~110 DEG C；Reaction time is 10~24h；Centrifugal process rotating speed
For 10000rpm, the time is 10min, and washing reagent is DMF and absolute ethyl alcohol, and washing times are 2~5 times；
Metal ion is zinc nitrate hexahydrate when synthesizing ZIF-8, and the amount weighed is 1.0~3.5g；Organic ligand is dimethyl miaow
Azoles, the amount weighed is 4.3~7.2g；Reaction dissolvent is methanol, and the amount measured is 50~200mL；Reaction temperature is 15~60 DEG C；
Reaction time is 0.5~12h；Centrifugal process rotating speed is 12000rpm, and the time is 15min, and washing reagent is methanol and anhydrous second
Alcohol, washing times are 2~5 times.
7. the surface-functionalized method of modifying of the metal-organic framework materials as claimed in claim 5 based on liposome membrane, its
It is characterised by, metal ion is Iron(III) chloride hexahydrate during synthesis MIL-100, the amount weighed is 1.0~3.5g；Organic ligand is
Trimesic acid, the amount weighed is 4.3~7.2g；Reaction dissolvent is the mixed solution of water and ethanol, the amount measured is 50~
200mL；Reaction temperature is 15~60 DEG C；Reaction time is 0.5~12h；Centrifugal process rotating speed is 12000rpm, and the time is
15min, washing reagent is methanol and absolute ethyl alcohol, and washing times are 2~5 times；
Synthesize MIL-101-NH2When metal ion be Iron(III) chloride hexahydrate, the amount weighed be 1.0~3.5g；Organic ligand is neighbour
Amino terephthalic acid (TPA), the amount weighed is 4.3~7.2g；Reaction dissolvent is that the amount measured is 50~200mL；Reaction temperature is
15~60 DEG C；Reaction time is 0.5~12h；Centrifugal process rotating speed is 12000rpm, and the time is 15min, and washing reagent is methanol
With absolute ethyl alcohol, washing times are 2~5 times.
8. the surface-functionalized method of modifying of the metal-organic framework materials as claimed in claim 1 based on liposome membrane, its
It is characterised by, the synthetic method of the liposome is specifically included：
Prepare liposome with extruder extrusion molding, various 2.5~10mg of lipid weighed by quality proportioning, be dissolved in 2~4mL chloroforms and
In the mixed solution of methanol, volume ratio is 4:1, dissolving be mixed thoroughly after in a water bath with Rotary Evaporators by organic solvent
Drain, be dried in vacuum overnight at room temperature；4~6ml HEPES buffer solution room temperature 1~2h of aquation are added, are then squeezed by liposome
Go out device to extrude 21 times, obtain final liposome.
9. the surface-functionalized method of modifying of the metal-organic framework materials as claimed in claim 8 based on liposome membrane, its
It is characterised by, quality proportioning is DOPA during the synthesis DOPA liposomes:chol：18:1PEG-2000PE=15:6:1, water-bath
Temperature is 35 DEG C；
The quality proportioning of lipid is DOPC when synthesizing DOPC liposomes:chol：18:1PEG-2000PE=15:6:1, bath temperature
For 25 DEG C；
The quality proportioning of lipid is DOPA when synthesizing DOTAP liposomes:chol：18:1PEG-2000PE=15:6:1, water-bath temperature
Spend for 40 DEG C.
10. a kind of function of surface of the metal-organic framework materials based on liposome membrane as described in claim 1~9 any one
Change the metal-organic framework materials of method of modifying modification.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710386696.XA CN107189074B (en) | 2017-05-26 | 2017-05-26 | Surface functional modification method of metal organic framework material based on liposome membrane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710386696.XA CN107189074B (en) | 2017-05-26 | 2017-05-26 | Surface functional modification method of metal organic framework material based on liposome membrane |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107189074A true CN107189074A (en) | 2017-09-22 |
| CN107189074B CN107189074B (en) | 2021-02-09 |
Family
ID=59874465
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710386696.XA Active CN107189074B (en) | 2017-05-26 | 2017-05-26 | Surface functional modification method of metal organic framework material based on liposome membrane |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107189074B (en) |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107722294A (en) * | 2017-11-17 | 2018-02-23 | 北京林业大学 | Microwave reaction method Fast back-projection algorithm MIL 88A type metal-organic framework materials |
| CN108129672A (en) * | 2017-12-18 | 2018-06-08 | 中南大学 | A kind of polymer changes the microwave synthesis method of MIL-53-Fe patterns |
| CN108525675A (en) * | 2018-04-08 | 2018-09-14 | 上海应用技术大学 | It is a kind of to prepare magnetic carbon/palladium-cobalt multiplex catalyst of aminated compounds, preparation method and application for being catalyzed reduction amination |
| CN109125266A (en) * | 2018-09-03 | 2019-01-04 | 南京大学 | The preparation method and application of liposome organometallic skeletal nanoscale medicine delivery system |
| CN109266636A (en) * | 2018-09-25 | 2019-01-25 | 江苏大学 | A kind of nano enzyme and its preparation method and application |
| CN109939081A (en) * | 2019-03-12 | 2019-06-28 | 武汉理工大学 | The nanometer organic metal framework material (nMOFs) and preparation method thereof of F3 polypeptide targeting |
| CN110152006A (en) * | 2019-05-22 | 2019-08-23 | 辽宁大学 | Hepatic targeting metal organic frame pharmaceutical carrier and its preparation method and application |
| CN110523282A (en) * | 2019-09-26 | 2019-12-03 | 东华大学 | A kind of compound forward osmosis membrane of UiO-66 and its preparation and application |
| CN111265533A (en) * | 2019-11-25 | 2020-06-12 | 上海纳米技术及应用国家工程研究中心有限公司 | Preparation method of core-shell nanoparticles based on lipid membrane and metal organic framework |
| CN111904946A (en) * | 2019-05-10 | 2020-11-10 | 西安电子科技大学 | Nano diagnosis and treatment preparation based on bionic rabies virus and preparation method and application thereof |
| CN112927769A (en) * | 2021-01-26 | 2021-06-08 | 华南理工大学 | MOFs material defect structure prediction method based on pore size distribution curve |
| CN113321815A (en) * | 2021-06-24 | 2021-08-31 | 天津工业大学 | MOF material with phospholipid bilayer grafted on surface, preparation method and application |
| CN114426676A (en) * | 2021-12-20 | 2022-05-03 | 南京师范大学 | Magnetic iron-based MOF microbial carrier material and preparation method thereof |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103083239A (en) * | 2012-12-26 | 2013-05-08 | 中国人民解放军第四军医大学 | Bufalin lipidosome, preparation method and application thereof |
| CN103920158A (en) * | 2014-04-24 | 2014-07-16 | 青岛大学 | Chitosan-functionalized metal organic framework materials as well as preparation method and application thereof |
| CN104128603A (en) * | 2014-08-13 | 2014-11-05 | 厦门大学 | Metal nanoparticle wrapped by zirconium-based porous shell and preparing method of metal nanoparticle |
| CN104352440A (en) * | 2014-11-07 | 2015-02-18 | 中国科学院过程工程研究所 | Cationic liposome nucleic acid medicinal preparation as well as preparation method and application thereof |
| CN105694051A (en) * | 2016-02-05 | 2016-06-22 | 山东师范大学 | Click chemistry based metal-organic framework cross-linking membrane and preparation method and application thereof |
| CN106366636A (en) * | 2016-09-05 | 2017-02-01 | 山东师范大学 | Metal-organic framework nanocrystal loaded polyurethane foam as well as preparation and application thereof |
| CN106492651A (en) * | 2016-11-08 | 2017-03-15 | 大连理工大学 | A kind of preparation of 66 series membranes of metallic organic framework UiO and the method for separating methyl alcohol/MTBE mixtures |
| CN106513017A (en) * | 2016-10-26 | 2017-03-22 | 华南理工大学 | Compound photocatalytic material and preparation method and application thereof |
| CN106674537A (en) * | 2017-01-25 | 2017-05-17 | 哈尔滨工业大学 | Template-free and solvent-free method for synthesizing metal organic framework material UiO-66 (Zr) rapidly and efficiently |
| CN106684355A (en) * | 2016-12-29 | 2017-05-17 | 中国电子科技集团公司第十八研究所 | Metal organic framework Uio-66@ S lithium sulfur positive electrode material and preparation method thereof |
-
2017
- 2017-05-26 CN CN201710386696.XA patent/CN107189074B/en active Active
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103083239A (en) * | 2012-12-26 | 2013-05-08 | 中国人民解放军第四军医大学 | Bufalin lipidosome, preparation method and application thereof |
| CN103920158A (en) * | 2014-04-24 | 2014-07-16 | 青岛大学 | Chitosan-functionalized metal organic framework materials as well as preparation method and application thereof |
| CN104128603A (en) * | 2014-08-13 | 2014-11-05 | 厦门大学 | Metal nanoparticle wrapped by zirconium-based porous shell and preparing method of metal nanoparticle |
| CN104352440A (en) * | 2014-11-07 | 2015-02-18 | 中国科学院过程工程研究所 | Cationic liposome nucleic acid medicinal preparation as well as preparation method and application thereof |
| CN105694051A (en) * | 2016-02-05 | 2016-06-22 | 山东师范大学 | Click chemistry based metal-organic framework cross-linking membrane and preparation method and application thereof |
| CN106366636A (en) * | 2016-09-05 | 2017-02-01 | 山东师范大学 | Metal-organic framework nanocrystal loaded polyurethane foam as well as preparation and application thereof |
| CN106513017A (en) * | 2016-10-26 | 2017-03-22 | 华南理工大学 | Compound photocatalytic material and preparation method and application thereof |
| CN106492651A (en) * | 2016-11-08 | 2017-03-15 | 大连理工大学 | A kind of preparation of 66 series membranes of metallic organic framework UiO and the method for separating methyl alcohol/MTBE mixtures |
| CN106684355A (en) * | 2016-12-29 | 2017-05-17 | 中国电子科技集团公司第十八研究所 | Metal organic framework Uio-66@ S lithium sulfur positive electrode material and preparation method thereof |
| CN106674537A (en) * | 2017-01-25 | 2017-05-17 | 哈尔滨工业大学 | Template-free and solvent-free method for synthesizing metal organic framework material UiO-66 (Zr) rapidly and efficiently |
Non-Patent Citations (2)
| Title |
|---|
| JUN LI, YANG YANG, LEAF HUANG: "Calcium phosphate nanoparticles with an asymmetric lipid bilayer coating for siRNA delivery to the tumor", 《JOURNL OF CONTROLLED RELEASE》 * |
| STEFAN WUTTKE ET AL.: "MOF nanoparticles coated by lipid bilayers and their uptake by cancer cells", 《CHEM.COMMUN.》 * |
Cited By (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107722294A (en) * | 2017-11-17 | 2018-02-23 | 北京林业大学 | Microwave reaction method Fast back-projection algorithm MIL 88A type metal-organic framework materials |
| CN108129672B (en) * | 2017-12-18 | 2020-01-07 | 中南大学 | Microwave synthesis method for changing shape of MIL-53-Fe by polymer |
| CN108129672A (en) * | 2017-12-18 | 2018-06-08 | 中南大学 | A kind of polymer changes the microwave synthesis method of MIL-53-Fe patterns |
| CN108525675A (en) * | 2018-04-08 | 2018-09-14 | 上海应用技术大学 | It is a kind of to prepare magnetic carbon/palladium-cobalt multiplex catalyst of aminated compounds, preparation method and application for being catalyzed reduction amination |
| CN109125266A (en) * | 2018-09-03 | 2019-01-04 | 南京大学 | The preparation method and application of liposome organometallic skeletal nanoscale medicine delivery system |
| CN109266636A (en) * | 2018-09-25 | 2019-01-25 | 江苏大学 | A kind of nano enzyme and its preparation method and application |
| CN109939081A (en) * | 2019-03-12 | 2019-06-28 | 武汉理工大学 | The nanometer organic metal framework material (nMOFs) and preparation method thereof of F3 polypeptide targeting |
| CN111904946A (en) * | 2019-05-10 | 2020-11-10 | 西安电子科技大学 | Nano diagnosis and treatment preparation based on bionic rabies virus and preparation method and application thereof |
| CN111904946B (en) * | 2019-05-10 | 2021-09-17 | 西安电子科技大学 | Nano diagnosis and treatment preparation based on bionic rabies virus and preparation method and application thereof |
| CN110152006A (en) * | 2019-05-22 | 2019-08-23 | 辽宁大学 | Hepatic targeting metal organic frame pharmaceutical carrier and its preparation method and application |
| CN110152006B (en) * | 2019-05-22 | 2023-02-28 | 辽宁大学 | Liver targeting metal organic framework drug carrier and preparation method and application thereof |
| CN110523282A (en) * | 2019-09-26 | 2019-12-03 | 东华大学 | A kind of compound forward osmosis membrane of UiO-66 and its preparation and application |
| CN110523282B (en) * | 2019-09-26 | 2021-11-09 | 东华大学 | UiO-66 composite forward osmosis membrane and preparation and application thereof |
| CN111265533A (en) * | 2019-11-25 | 2020-06-12 | 上海纳米技术及应用国家工程研究中心有限公司 | Preparation method of core-shell nanoparticles based on lipid membrane and metal organic framework |
| WO2021103232A1 (en) * | 2019-11-25 | 2021-06-03 | 上海纳米技术及应用国家工程研究中心有限公司 | Preparation method for core-shell nanoparticles based on lipid membrane and metal organic framework |
| CN111265533B (en) * | 2019-11-25 | 2023-07-18 | 上海纳米技术及应用国家工程研究中心有限公司 | Preparation method of core-shell nano-particles based on lipid membrane and metal organic framework |
| CN112927769A (en) * | 2021-01-26 | 2021-06-08 | 华南理工大学 | MOFs material defect structure prediction method based on pore size distribution curve |
| CN112927769B (en) * | 2021-01-26 | 2022-05-24 | 华南理工大学 | MOFs material defect structure prediction method based on pore size distribution curve |
| CN113321815A (en) * | 2021-06-24 | 2021-08-31 | 天津工业大学 | MOF material with phospholipid bilayer grafted on surface, preparation method and application |
| CN114426676A (en) * | 2021-12-20 | 2022-05-03 | 南京师范大学 | Magnetic iron-based MOF microbial carrier material and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107189074B (en) | 2021-02-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107189074A (en) | The surface-functionalized method of modifying of metal-organic framework materials based on liposome membrane | |
| Kumar et al. | Formulation strategies for folate-targeted liposomes and their biomedical applications | |
| Cˇeh et al. | Stealth® liposomes: from theory to product | |
| McLEAN et al. | Organ-specific endothelial cell uptake of cationic liposome-DNA complexes in mice | |
| Sohrabi et al. | Nanoscale Metal-Organic Frameworks: Recent developments in synthesis, modifications and bioimaging applications | |
| Yang et al. | Lipid, protein and poly (NIPAM) coated mesoporous silica nanoparticles for biomedical applications | |
| AU769497B2 (en) | Nanocapsules and method of production thereof | |
| Zhang et al. | The optimized fabrication of a novel nanobubble for tumor imaging | |
| Cheng et al. | Paramagnetic porous polymersomes | |
| Gan et al. | Protein corona of metal-organic framework nanoparticals: Study on the adsorption behavior of protein and cell interaction | |
| CN102008441B (en) | Endoglin antibody coupled liposome as well as preparation method and application thereof | |
| CN113292608B (en) | Exosome drug delivery system and preparation method and application thereof | |
| JP2003525258A (en) | Nanocapsules with one polyelectrolyte jacket | |
| Crielaard et al. | An in vitro assay based on surface plasmon resonance to predict the in vivo circulation kinetics of liposomes | |
| Beztsinna et al. | Photoacoustic imaging of tumor targeting with riboflavin-functionalized theranostic nanocarriers | |
| Baa et al. | Current Trend in Synthesis, Post‐Synthetic Modifications and Biological Applications of Nanometal‐Organic Frameworks (NMOFs) | |
| Lerner et al. | Synthesis and properties of new multilayer chitosan@ layered double hydroxide/drug loaded phospholipid bilayer nanocomposite bio-hybrids | |
| Li et al. | Prussian blue nanoparticle-loaded microbubbles for photothermally enhanced gene delivery through ultrasound-targeted microbubble destruction | |
| CN110612097B (en) | Liposome drug delivery vehicle | |
| Knudsen et al. | Biodistribution of rhodamine B fluorescence-labeled cationic nanoparticles in rats | |
| Suzuki et al. | Impact of spontaneous liposome modification with phospholipid polymer-lipid conjugates on protein interactions | |
| Rezler et al. | Peptide-mediated targeting of liposomes to tumor cells | |
| CN1839799B (en) | Agglutinin-modified drug delivery system from nose to brain | |
| Szabová et al. | N, N, N-Trimethyl chitosan as a permeation enhancer for inhalation drug delivery: interaction with a model pulmonary surfactant | |
| CN105001370B (en) | Copolymer and liposome complex with temperature, pH responsiveness |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |