CN107469092A - Targeted nanometer material preparation method and products thereof and application - Google Patents
Targeted nanometer material preparation method and products thereof and application Download PDFInfo
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- A61K49/0002—General or multifunctional contrast agents, e.g. chelated agents
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- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0054—Macromolecular compounds, i.e. oligomers, polymers, dendrimers
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- 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
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0056—Peptides, proteins, polyamino acids
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- 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
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0058—Antibodies
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- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0089—Particulate, powder, adsorbate, bead, sphere
- A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
- A61K49/0093—Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/12—Macromolecular compounds
- A61K49/126—Linear polymers, e.g. dextran, inulin, PEG
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/14—Peptides, e.g. proteins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/14—Peptides, e.g. proteins
- A61K49/16—Antibodies; Immunoglobulins; Fragments thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5123—Organic compounds, e.g. fats, sugars
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5169—Proteins, e.g. albumin, gelatin
Abstract
The present invention relates to a kind of targeted nanometer material and its preparation method and application, specifically by the Zn to high magnetic saturation value0.4Fe2.6O4Nano particle carries out pegylation, while contains anti-tumor drug molecule, prepares and collects targeting, Double-mode imaging and treat in the nano material system of integration.On the one hand this nano material system can embody the high magnetic of its center core and the outer double dominant for carrying the good biocompatibility of liposome and biological degradability, on the other hand, its targeted molecular being connected on outer layer PEG polymerizable moleculars and fluorescence molecule can play the targeting of nano particle and the effect of dual imaging again, therefore it is in biomedical sector, especially in targeting diagnosis and carries medicine etc. and has potential application prospect.
Description
Technical field
The invention belongs to nano biological medical material field, is related to a kind of targeted nanometer material preparation method and products thereof
And application.Specifically by the Zn to high magnetic saturation value0.4Fe2.6O4Nano particle carries out pegylation, contains simultaneously
Anti-tumor drug molecule, prepare and collect targeting, Double-mode imaging and treat in the nano material system of integration.
Background technology
Cancer is to threaten a kind of means and methodses such as major disease, conventional chemotherapy, radiotherapy and operative treatment of human life
Effect is unsatisfactory.Therefore, it is extremely urgent for cancer diagnosis and treatment to develop new technology, and early diagnosis and the height of cancer can be realized
It is that current treatment of cancer urgent problem is crucial to imitate nontoxic drug therapy.Nano-particle small-size effect, can
It is specific to penetrate tumor tissues depths, therefore the cancer diagnosis and treatment that develop into of nano material bring new hope.Nano material
Drug-loading system can not only can also extend the circulation time of medicine in vivo by enhanced permeability and retention effect (EPR), improve
The therapeutic efficiency of medicine.In addition, contrast agent of the nano material as bio-imaging, the function that can monitor internal cell in real time becomes
Change, and preclinical disease can be detected.Therefore, by optimizing material, stable, the efficient and safe nano-carrier of structure, and
Integrating the functions such as drug targeting transport, vivo tracking, drug therapy and Prognosis scoveillance will be in integral multifunctional nano system
Following research tendency.
Magnetic nanoparticle has unique magnetic property, surface is easily modified and good biocompatibility, therefore it is facing
The orientation treatment of bed diagnosis and disease has obtained extensive concern.Exposed magnetic nanoparticle during blood circulation, when
By being easily eliminated away when biological protection systems and vascular barrier, it is accumulated at liver, kidney and lymph node.Pass through surface
Modification, such as amphipathic molecule, the Polymeric ligands either biomolecule of Biofunctional, can prevent magnetic nanoparticle
Reunite, increase colloidal stability.Use polyethylene glycol（PEG）Having become one kind to nano particle progress surface modification prevents net
A kind of common method of shape endothelial system phagocytosis, this can extend the sanguimotor half period of nano particle and improve real
The permeability and retention effect of body knurl（EPR）（Adv Funct Mater, 2011,21,1498-504）.Therefore, preparation has
Targeting, dual imaging pattern and the magnetic Nano system for the treatment of have higher Research Significance and application value.
The content of the invention
In view of the shortcomings of the prior art, present invention aims at：A kind of targeted nanometer material preparation method is provided.
Another object of the present invention is：The product that above-mentioned preparation method obtains is provided.
A further object of the present invention is：The application of the product is provided.
Pass through the Zn to high magnetic saturation value0.4Fe2.6O4Nano particle carries out pegylation, while contains anticarcinogen
Thing molecule, prepare collect targeting, Double-mode imaging in integration nano material system,
To achieve the above object, the present invention adopts the following technical scheme that：
The preparation method of targeted nanometer material, it is characterised in that：Comprise the following steps：
（1）Oiliness Zn0.4Fe2.6O4The preparation of nano particle：
FeSO4·(NH4)2SO4·6H2O and ZnSO4It is dissolved in water so that precursor reaches 1.73 × 10-3 mol Fe2+
and 2.67×10-4 mol Zn2+, oleic acid, absolute ethyl alcohol and NaOH are mixed, magnetic agitation is until obtaining uniformly at normal temperatures
Solution, precursor Fe2+And Zn2+Pour into the homogeneous solution, after stirring a few minutes, mixed solution becomes dark-brown, finally handle
The solution is transferred into as in 50ml reactors, sealing, 230 DEG C of 15 hours of heating, after reaction terminates, is cooled to room temperature, is produced
Product are deposited on bottom, add n-hexane, take out nano particle, then ethanol is added in n-hexane, are settled out nano particle, finally
Nano particle is washed for several times repeatedly with ethanol again, is removed impurity, is obtained pegylation Zn0.4Fe2.6O4Nano particle disperses
In n-hexane, 4 DEG C of preservations are carried out；
（2）The targeting modification of phospholipid molecule：
DSPE-PEG2000 phospholipid molecules with functional group are dissolved in DMF（DMF）In, stir,
Then targeted molecular is dissolved in phosphate buffer（PBS, pH 7.0）, the two mixing, ultrasonic bubble removing, magnetic agitation 1h
Afterwards, appropriate dilution, C4Post HPLC sample detection extent of reactions, bag filter remove impurity, and freeze-drying obtains targeted molecular modification
DSPE-PEG2000 phospholipid molecules；
（3）The preparation of targeted nanometer material
By targeted molecular modification DSPE-PEG2000 phospholipid molecules, fluorescence molecule modification DSPE-PEG2000 phospholipid molecules and
Cancer therapy drug is dissolved in chloroform, and is added to and is dispersed with Zn0.4Fe2.6O4In the n-hexane of nano particle, ultrasonic disperse is uniform
Afterwards, deionized water is slowly added dropwise in above-mentioned mixed solution, finally, 70 DEG C rotate 15 minutes, and it is unnecessary that Magneto separate removes
Liposome, last targeted nanometer particle are dispersed in water 4 DEG C and are kept in dark place.
Described targeted molecular is in c (RGDyK), folic acid (HA), IL-13p, CD163 antibody, Ly6C antibody, mannose
One kind.
The functional group of the described DSPE-PEG2000 phospholipid molecules institute band with functional group is carboxyl, amino, Malaysia acyl
One kind in imines.
Described fluorescence molecule is fluorescein isothiocynate（FITC）, change blue or green element（CY5）, in rhodamine isothiocyanates
It is a kind of.
Described cancer therapy drug is one kind in taxol, vinblastine, cytarabine, lomustine.
The present invention provides the targeted nanometer material system that a kind of any of the above-described methods described is prepared.
The present invention provides a kind of targeted nanometer material system as targeting and the application of medicine carrying material.This nano material
On the one hand system can embody the high magnetic of its center core and biocompatibility and biological degradability that outer load liposome is good
Double dominant, on the other hand, its targeted molecular being connected on outer layer PEG polymerizable moleculars and fluorescence molecule can be played and received again
The targeting of rice grain and the effect of dual imaging, therefore it is in biomedical sector, especially in targeting diagnosis and carries medicine etc.
Aspect has potential application prospect.
The advantage of the invention is that：
（1）Nano material prepared by the present invention has the function of fluorescence and magnetic double-mode imaging.
（2）Nano material prepared by the present invention has the function of selectively targeted tumour.
（3）Nano material prepared by the present invention has the function for the treatment of tumour.
（4）The present invention, which prepares nano material, has good biocompatibility and the macrocyclic function of blood, so as to have
Effect improves the effect of its diagnosis and treatment.
（5）Magnetic nanoparticle prepared by the present invention has higher magnetic saturation value.
（6）Preparation method technique of the present invention is simple, workable, further can meet to produce and apply.
Brief description of the drawings
Fig. 1 is the transmission electron microscope of the nano material prepared by embodiment 1（TEM）Figure；
Fig. 2 is the TEM figures of the nano material prepared by embodiment 2；
Fig. 3 is the TEM figures of the nano material prepared by embodiment 3；
Fig. 4 is the TEM figures of the nano material prepared by embodiment 4.
Embodiment
Technical scheme is further described below by way of specific embodiment.Following embodiment is to this
The further explanation of invention, and do not limit the scope of the invention.
Embodiment 1
1. oiliness Zn0.4Fe2.6O4The preparation of nano particle
FeSO4·(NH4)2SO4·6H2O and ZnSO4It is dissolved in 20ml water so that precursor reaches 1.73 × 10-3 mol
Fe2+ and 2.67×10-4 mol Zn2+Purpose；10ml oleic acid, 10ml absolute ethyl alcohols and 1g NaOH are mixed, in normal temperature
Lower magnetic agitation is until obtaining homogeneous solution；Precursor Fe2+And Zn2+Pour into the homogeneous solution, after stirring a few minutes, mix
Close solution and become dark-brown.Finally the solution is transferred into 50ml reactors, sealed, 230 degree of 15 hours of heating, reaction knot
Shu Yihou, it is cooled to room temperature, product oiliness Zn0.4Fe2.6O4Nanoparticle deposition is in bottom, addition n-hexane, taking-up nanometer
Grain；Ethanol is added in n-hexane again, is settled out nano particle, last nano particle is washed for several times, except impurity elimination repeatedly with ethanol again
Matter, obtain pegylation nano particle and be dispersed in n-hexane, 4 degree of preservations.
2. the targeting modification of phospholipid molecule
DSPE-PEG2000 phospholipid molecules of the 1mol with functional group is dissolved in 0.5mlDMF（DMF）, stir
Mix uniformly；1.2mol targeted moleculars are dissolved in 1ml phosphate buffers（PBS, pH 7.0）, the two mixing, ultrasonic degasification
Steep, after magnetic agitation 1h, appropriate dilution, C4Post HPLC sample detection extent of reactions, bag filter remove impurity, and freeze-drying obtains
The DSPE-PEG2000 phospholipid molecules of targeted molecular modification.
3. the preparation of the integrated magnetic Nano material of targeting, diagnosis and treatment
DSPE-PEG2000 phospholipid molecules, the DSPE- of 8.5mg fluorescence molecules modification that 8.5mg targeted moleculars are modified first
PEG2000 phospholipid molecules and 25.5mg cancer therapy drugs are dissolved in 5ml chloroforms, and are added to 5ml and are dispersed with Zn0.4Fe2.6O4Receive
Rice grain（5mg）N-hexane in, ultrasonic disperse is uniform.Secondly, 5ml deionized waters are slowly added dropwise above-mentioned mixed solution
In, 70 degree rotate 15 minutes, and Magneto separate removes unnecessary liposome, and last targeted nanometer particle is dispersed in water 4 degree of lucifuges
Preserve.
Fig. 1 is the TEM figures of the nano material prepared by the present embodiment.
Embodiment 2
1. oiliness Zn0.4Fe2.6O4The preparation of nano particle
First FeSO4·(NH4)2SO4·6H2O and ZnSO4It is dissolved in 20ml water so that precursor reaches 1.73 × 10-3
mol Fe2+ and 2.67×10-4 mol Zn2+Purpose；10ml oleic acid, 10ml absolute ethyl alcohols and 1g NaOH are mixed,
Magnetic agitation is until obtaining homogeneous solution under normal temperature；Precursor Fe2+And Zn2+Pour into the homogeneous solution, stirring a few minutes with
Afterwards, mixed solution becomes dark-brown, and finally the solution is transferred into 50ml reactors, sealing, 230 degree of 15 hours of heating,
After reaction terminates, room temperature is cooled to, product is deposited on bottom, adds n-hexane, takes out nano particle.Again ethanol add just oneself
In alkane, nano particle is settled out, last nano particle is washed for several times repeatedly with ethanol again, removes impurity, oiliness Zn0.4Fe2.6O4Receive
Rice grain is dispersed in n-hexane, 4 degree of preservations.
2. the targeting modification of phospholipid molecule
DSPE-PEG2000 phospholipid molecules of the 1mol with functional group is dissolved in 0.5mlDMF first（N, N- dimethyl formyl
Amine）, stir.Secondly 1.2mol targeted moleculars are dissolved in 1ml phosphate buffers（PBS, pH 7.0）.The two is mixed
Close, ultrasonic bubble removing, after magnetic agitation 1h, appropriate dilution.C4Post HPLC sample detection extent of reactions.Bag filter removes impurity,
Freeze-drying obtains the DSPE-PEG2000 phospholipid molecules of targeted molecular modification.
3. the preparation of the integrated magnetic Nano material of targeting, diagnosis and treatment
DSPE-PEG2000 phospholipid molecules, the DSPE- of 8.5mg fluorescence molecules modification that 8.5mg targeted moleculars are modified first
PEG2000 phospholipid molecules and 25.5mg cancer therapy drugs are dissolved in 5ml chloroforms, and are added to 5ml and are dispersed with Zn0.4Fe2.6O4Receive
Rice grain（5mg）N-hexane in, ultrasonic disperse is uniform.Secondly, 5ml deionized waters are slowly added dropwise above-mentioned mixed solution
In, 70 degree rotate 20 minutes, and Magneto separate removes unnecessary liposome, and last targeted nanometer particle is dispersed in water 4 degree of lucifuges
Preserve.
Fig. 2 is the TEM figures for originally applying the nano material prepared by example.
Embodiment 3
1. oiliness Zn0.4Fe2.6O4The preparation of nano particle
First FeSO4·(NH4)2SO4·6H2O and ZnSO4It is dissolved in 20ml water so that precursor reaches 1.73 × 10-3
mol Fe2+ and 2.67×10-4 mol Zn2+Purpose.Secondly, 10ml oleic acid, 10ml absolute ethyl alcohols and 1g NaOH are mixed
Close, magnetic agitation is until obtaining uniform solution at normal temperatures.Furthermore precursor Fe2+And Zn2+Pour into the homogeneous solution, stir
After mixing a few minutes, mixed solution becomes dark-brown.Finally the solution is transferred into 50ml reactors, sealed, 230 degree of heating
15 hours.After reaction terminates, room temperature is cooled to.Product is deposited on bottom, adds n-hexane, takes out nano particle.Again
Ethanol is added in n-hexane, is settled out nano particle, and last nano particle is washed for several times repeatedly with ethanol again, removes impurity.Nanometer
Particle is dispersed in n-hexane, 4 degree of preservations.
2. the targeting modification of phospholipid molecule
DSPE-PEG2000 phospholipid molecules of the 1mol with functional group is dissolved in 0.5mlDMF first（N, N- dimethyl formyl
Amine）, stir.Secondly 1.2mol targeted moleculars are dissolved in 1ml phosphate buffers（PBS, pH 7.0）.The two is mixed
Close, ultrasonic bubble removing, after magnetic agitation 1h, appropriate dilution.C4Post HPLC sample detection extent of reactions.Bag filter removes impurity,
Freeze-drying obtains the DSPE-PEG2000 phospholipid molecules of targeted molecular modification.
3. the preparation of the integrated magnetic Nano material of targeting, diagnosis and treatment
DSPE-PEG2000 phospholipid molecules, the DSPE- of 17mg fluorescence molecules modification that 17mg targeted moleculars are modified first
PEG2000 phospholipid molecules and 51mg cancer therapy drugs are dissolved in 5ml chloroforms, and are added to 5ml and are dispersed with Zn0.4Fe2.6O4Nanometer
Particle（5mg）N-hexane in, ultrasonic disperse is uniform.Secondly, 5ml deionized waters are slowly added dropwise above-mentioned mixed solution
In.Finally, 70 degree rotate 15 minutes.Magneto separate removes unnecessary liposome, and last nano particle is dispersed in water 4 degree of lucifuges and protected
Deposit.
Fig. 3 is the TEM figures of the nano material prepared by the present embodiment 3.
Embodiment 4
1. oiliness Zn0.4Fe2.6O4The preparation of nano particle
First FeSO4·(NH4)2SO4·6H2O and ZnSO4It is dissolved in 20ml water so that precursor reaches 1.73 × 10-3
mol Fe2+ and 2.67×10-4 mol Zn2+Purpose.Secondly, 10ml oleic acid, 10ml absolute ethyl alcohols and 1g NaOH are mixed
Close, magnetic agitation is until obtaining uniform solution at normal temperatures.Furthermore precursor Fe2+And Zn2+Pour into the homogeneous solution, stir
After mixing a few minutes, mixed solution becomes dark-brown.Finally the solution is transferred into 50ml reactors, sealed, 230 degree of heating
15 hours.After reaction terminates, room temperature is cooled to.Product is deposited on bottom, adds n-hexane, takes out nano particle.Again
Ethanol is added in n-hexane, is settled out nano particle, and last nano particle is washed for several times repeatedly with ethanol again, removes impurity.Nanometer
Particle is dispersed in n-hexane, 4 degree of preservations.
2. the targeting modification of phospholipid molecule
DSPE-PEG2000 phospholipid molecules of the 1mol with functional group is dissolved in 0.5mlDMF first（N, N- dimethyl formyl
Amine）, stir.Secondly 1.2mol targeted moleculars are dissolved in 1ml phosphate buffers（PBS, pH 7.0）.The two is mixed
Close, ultrasonic bubble removing, after magnetic agitation 1h, appropriate dilution.C4Post HPLC sample detection extent of reactions.Bag filter removes impurity,
Freeze-drying obtains the DSPE-PEG2000 phospholipid molecules of targeted molecular modification.
3. the preparation of the integrated magnetic Nano material of targeting, diagnosis and treatment
DSPE-PEG2000 phospholipid molecules, the DSPE- of 8.5mg fluorescence molecules modification that 8.5mg targeted moleculars are modified first
PEG2000 phospholipid molecules and 25.5mg cancer therapy drugs are dissolved in 5ml chloroforms, and are added to 5ml and are dispersed with Zn0.4Fe2.6O4Receive
Rice grain（10mg）N-hexane in, ultrasonic disperse is uniform.Secondly, it is molten that 5ml deionized waters are slowly added dropwise above-mentioned mixing
In liquid.Finally, 70 degree rotate 15 minutes.Magneto separate removes unnecessary liposome, and last nano particle is dispersed in water 4 degree of lucifuges
Preserve.
Fig. 4 is the TEM figures of the nano material prepared by the present embodiment 4.
Claims (7)
1. the preparation method of targeted nanometer material, pass through the Zn to high magnetic saturation value0.4Fe2.6O4Nano particle carries out poly- second two
Alcoholization modification, while contains anti-tumor drug molecule, prepares and collects targeting, Double-mode imaging in the nano material system of integration,
Comprise the following steps：
（1）Oiliness Zn0.4Fe2.6O4The preparation of nano particle：
FeSO4·(NH4)2SO4·6H2O and ZnSO4It is dissolved in water so that precursor reaches 1.73 × 10-3 mol Fe2+ and
2.67×10-4 mol Zn2+, oleic acid, absolute ethyl alcohol and NaOH are mixed, magnetic agitation is uniformly molten until obtaining at normal temperatures
Liquid, precursor Fe2+And Zn2+Pour into the homogeneous solution, after stirring a few minutes, mixed solution becomes dark-brown, finally this
Solution is transferred into reactor, sealing, 230 DEG C of 15 hours of heating, after reaction terminates, is cooled to room temperature, product is deposited on
Bottom, n-hexane is added, take out nano particle, then ethanol is added in n-hexane, be settled out nano particle, last nano particle
Washed repeatedly with ethanol again for several times, remove impurity, obtain pegylation Zn0.4Fe2.6O4Nano particle is dispersed in n-hexane
In, 4 DEG C of preservations；
（2）The targeting modification of phospholipid molecule：
DSPE-PEG2000 phospholipid molecules with functional group are dissolved in DMF（DMF）, stir, will
Targeted molecular is dissolved in phosphate buffer（PBS, pH7.0）, the two is mixed, ultrasonic bubble removing, after magnetic agitation 1h, suitably
Dilution, C4Post HPLC sample detection extent of reactions, bag filter remove impurity, and freeze-drying obtains the DSPE- of targeted molecular modification
PEG2000 phospholipid molecules；
（3）The preparation of targeted nanometer material：
By targeted molecular modification DSPE-PEG2000 phospholipid molecules, fluorescence molecule modification DSPE-PEG2000 phospholipid molecules and
Cancer therapy drug is dissolved in chloroform, and is added to and is dispersed with Zn0.4Fe2.6O4In the n-hexane of nano particle, ultrasonic disperse is uniform,
Then, deionized water is slowly added dropwise in above-mentioned mixed solution, finally, 70 DEG C rotate 15 minutes, and it is unnecessary that Magneto separate removes
Liposome, last targeted nanometer particle is dispersed in water 4 DEG C and is kept in dark place.
2. the preparation method of targeted nanometer material according to claim 1, it is characterised in that：Described targeted molecular is
One kind in c (RGDyK), folic acid (HA), IL-13p, CD163 antibody, Ly6C antibody, mannose.
3. the preparation method of targeted nanometer material according to claim 1, it is characterised in that：Described carries functional group
DSPE-PEG2000 phospholipid molecules institute band functional group be carboxyl, amino, one kind in maleimide.
4. the preparation method of targeted nanometer material according to claim 1, it is characterised in that：Described fluorescence molecule is
Fluorescein isothiocynate（FITC）, change blue or green element（CY5）, one kind in rhodamine isothiocyanates.
5. the preparation method of targeted nanometer material according to claim 1, it is characterised in that：Described cancer therapy drug is
One kind in taxol, vinblastine, cytarabine, lomustine.
A kind of 6. targeted nanometer material product obtained according to any preparation methods of claim 1-5.
7. targeted nanometer material according to claim 6 is as targeting and the application of medicine carrying material.
Priority Applications (1)
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|---|---|---|---|
| CN201710666507.4A CN107469092A (en) | 2017-08-07 | 2017-08-07 | Targeted nanometer material preparation method and products thereof and application |
Applications Claiming Priority (1)
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