CN108619534A - Multi-functional self-assemblies of a kind of GA-Fe@BSA-PTX and its preparation method and application - Google Patents
Multi-functional self-assemblies of a kind of GA-Fe@BSA-PTX and its preparation method and application Download PDFInfo
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Abstract
The present invention relates to multi-functional self-assemblies of a kind of GA Fe@BSA PTX and its preparation method and application, and preparation method includes the following steps：(1) mixed solution of bovine serum albumin and soluble ferric iron salt will be prepared；(2) under stiring, gallic acid is added in mixed solution and is reacted, purified after reaction, obtain pure GA Fe@BSA nano-particle solutions；(3) after GA Fe@BSA aqueous solutions being added in buffer solution, PTX solution reactions is added with stirring, are purified after reaction, GA Fe@BSA PTX nano-particle solutions are obtained.Compared with prior art, preparation method of the present invention simply easily repeats, selected raw material inexpensive safety is nontoxic, gained coordination polymer nano dot good biocompatibility, bio-toxicity are low, it can be used for the highly sensitive Magnetic resonance imaging of tumour, and at the same time having chemotherapy and photo-thermal therapy double treatment function, more effective therapeutic effect can be played to tumour.
Description
Technical field
The present invention relates to material science and bio-medical field, multi-functional certainly more particularly, to a kind of GA-Fe@BSA-PTX
Assembly and its preparation method and application.
Background technology
Now, malignant tumour because of its death rate height, refractory treatment and deteriorates the features such as rapid, and it is strong to have seriously threatened the mankind
Health.Diagnosis and treatment integrated technique is most to hold promise for a kind of method for the treatment of malignant tumour, and tumour integration reagent is diagnosis and treatment
The key of integrated technique development.A variety of diagnosis and treatment integration reagents have now been developed, wherein nuclear magnetic resonance (MR) image is situated between
The integration diagnosis and treatment reagent such as photo-thermal, chemotherapy for leading has broad application prospects.It is primarily due to, MR image technologies have non-invade
Enter, the advantages such as tissue penetration is deep, is widely used in the diagnosis of lesion earlier specificity and examination of curative effect.And photo-thermal therapy technology profit
It is very strong to the penetration capacity of biological tissue with the near-infrared laser for being 700-1400nm using wave-length coverage, but pain is smaller,
And thorough treatment, it is smaller to the damage of normal surrounding tissue, it is a kind of Micro trauma oncotherapy means.Chemotherapy is a kind of traditional
Cancer Treatment Regimens, but it is a problem to be solved the toxicity of immune system.
Bovine serum albumin(BSA) (BSA) is a kind of albumin in cow's serum, can with it is a variety of cation, anion and
Small-molecule substance causes everybody earnestly to pay close attention in conjunction with this property.Moreover, BSA because of abundance, is easy purifying, price is just
Preferably, dissolubility is good in water, many advantages, such as organism easily biological-degradable, nontoxicity, non-immunogenicity, is widely used
In the fields such as drug delivery and nano material synthesis.At present it has been reported that a variety of inorganic nano materials for giving BSA synthesis,
The synthesis (Adv.Mater., 2016,28,5923) of especially extra small nano material, our regulation and control of the research group based on BSA
Design synthesized a kind of extra small coordination polymer nano-particle (International journal of nanomedicine,
2017,12,7207).But this kind of material there is a problem of one very big, if grain size is too big, it is difficult metabolism to lead to material, long
Phase is detained in vivo, has prodigious security risk；And if grain size is too small, it is easy to system is removed by kidney and is excluded in vitro, this
Sample is difficult to effectively be enriched in lesions position.Therefore in order to solve this problem, need exploitation is a kind of being based on extra small nano-particle
Self-assembled material solve the above contradiction.
Taxol (PTX) is the broad-spectrum anti-cancer drug for being used to treat the cancers such as breast cancer, oophoroma, lung cancer in the market, because
Its water solubility is very low, and very big inconvenience is brought to its use.Recent study discovery, albumin combination type paclitaxel nano system
Agent effectively solves the problems, such as taxol soluble, and toxicity is also alleviated while improving curative effect.Wherein significantly PTX
BSA can be assembled by hydrophobic phase interaction, builds the self-assembly based on BSA.On the one hand the water of PTX can be solved
On the other hand dissolubility problem can improve its bio-compatibility.But existing albumin type drug be used for heat cure when, face
Facing prevents the heat shock response of cancer cell overheat, and the mechanism of this cancer cell protection and anti-apoptosis reduces the efficiency of thermotherapy.
Invention content
It is an object of the present invention to overcome the above-mentioned drawbacks of the prior art and provide a kind of GA-Fe@BSA-PTX
Multi-functional self-assembly and its preparation method and application.
The purpose of the present invention can be achieved through the following technical solutions：
A kind of preparation method of the multi-functional self-assemblies of GA-Fe@BSA-PTX, includes the following steps：
(1) bovine serum albumin is dissolved in secondary water, is added with stirring soluble trivalent iron salt, obtains mixed solution A；
(2) under stiring, gallic acid is added and is reacted into mixed solution A, purified after reaction, obtained pure
GA-Fe@BSA coordination polymer nano-particle aqueous solutions；
(3) GA-Fe@BSA coordination polymer nano-particle aqueous solutions are added in buffer solution, obtains mixed solution B, stirs
It mixes down, PTX solution reactions is added in mixed solution B, are purified after reaction, you can obtain GA-Fe@BSA-PTX and receive
Rice corpuscles solution, the GA-Fe@BSA-PTX nano-particles are the multi-functional self-assemblies of GA-Fe@BSA-PTX.
Preferably, in step (1), the mass concentration of bovine serum albumin is 0~3.0mg/mL in the mixed solution A,
But it is not 0.
Preferably, in step (1), the soluble trivalent iron salt is one kind of iron chloride, ferric nitrate or ferric sulfate, and
The mass concentration of soluble trivalent iron salt is 0~3.0g/mL in mixed solution A, but is not 0.
Preferably, in step (2), the mass concentration of gallic acid is 0~30.0mg/mL in mixed solution A.
Preferably, in step (3), the buffer solution be PBS solution, pH be 5~10, a concentration of 0~0.3mol/L,
But it is not 0.
Preferably, in step (3), the dispersion solvent of the PTX solution is ethyl alcohol, and feed postition is to be added dropwise, and is mixed
The mass concentration for closing PTX in solution B is 0~40.0 μ g/mL, but is not 0.
Preferably：
In step (2), reaction time 3-24h, reaction temperature is room temperature；
In step (3), the reaction time is 0~5h, but is not 0, and reaction temperature is room temperature.
Preferably：
In step (2), purification process is to be centrifuged after reaction, obtains sediment, is washed with water and washs precipitation
Object；
In step (3), purification process is to be centrifuged after reaction, obtains sediment, is washed with water and washs precipitation
Object.
The multi-functional self-assemblies of GA-Fe@BSA-PTX being prepared using the method, the self-assembly pass through use
BSA carries out modification regulation and control to GA-Fe and obtains extra small GA-Fe@BSA coordination polymerization nano-particles, recycles the hydrophobic assembling eggs of PTX
Extra small GA-Fe@BSA coordination polymerization nano-particles are assembled to obtain by the performance of white matter.
First, it is based on BSA and is rich in the ends N- and O- terminal amino acid residues, these sites and transition-metal Fe3+Have and matches by force
Position effect forms BSA-Fe by the way that soluble trivalent iron salt aqueous solution is added to BSA aqueous solutions3+Complex.Secondly, pass through to
BSA-Fe3+GA monomers are added in complex, the phenolic hydroxyl group and carboxyl in GA groups and Fe3+Chelating forms GA-Fe@BSA polycomplexations
Close nano-particle.Finally, using the performance of the hydrophobic assembling protein of taxol (PTX), extra small GA-Fe@BSA coordination polymerizations are received
Rice corpuscles assembles, and obtains GA-Fe@BSA-PTX nano-particles, the i.e. multi-functional self-assemblies of GA-Fe@BSA-PTX.
Preferably, the grain size about 100nm of the multi-functional self-assemblies of GA-Fe@BSA-PTX, single point spherical in shape of pattern
Dissipate nano particle.
The multi-functional self-assemblies of GA-Fe@BSA-PTX are controlled in mri contrast agent and/or photo-thermal-chemotherapy combined
Treat the application on drug.
Extra small GA-Fe@BSA nano materials are assembled the invention discloses a kind of PTX, the material is because of its suitable grain size
(~100nm) can effectively improve extra small GA-Fe@BSA nano materials tumour enrichment, while also have extra small GA-
The kidney elimination effect of Fe@BSA nano materials.In addition, the material makes relative to extra small GA-Fe@BSA nano materials after assembling
It obtains and contains multiple GA-Fe@BSA nano-particles in a nano particle, thus there is better MR imaging functions and photo-thermal-change
The effect for treating combination therapy, effectively raises the therapeutic effect of cancer.
The polymer nano-particle of multiple cladding albumin is assembled by the present invention using the hydrophobic self assembly performance of drug
The polymer nano-particle of one nano particle, albumin combination not only has stronger absorption, Er Qieyou near infrared region
The hydrophobic self assembly effect promoted in drug, maintains good biocompatibility and stability, improve nuclear magnetic resonance at
As effect, also while having the function of good photo-thermal and chemotherapy double treatment, more effective therapeutic effect can be played to tumour.
Compared with prior art, the invention has the advantages that：
(1) present invention forms nano-particle using the organic polymer of the albumin regulation and control easily biological-degradable of non-toxic inexpensive,
Preparation method is simple, at low cost, and dispersing agent performance obtained is excellent and stability is good, can absorb near infrared light well；
(2) multi-functional self-assemblies of GA-Fe@BSA-PTX produced by the present invention, not only with good nuclear magnetic resonance at
As effect, also while having the function of photo-thermal and chemotherapy double treatment.
Description of the drawings
Fig. 1 is the multi-functional self-assembly composite structure schematic diagrames of GA-Fe@BSA-PTX.
Fig. 2 is that the TEM for the multi-functional self-assemblies of GA-Fe@BSA-PTX that embodiment 1 is prepared schemes (a) and SEM spectrum
(b) figure.
Fig. 3 is the UV absorption figure for the multi-functional self-assemblies of GA-Fe@BSA-PTX that embodiment 1 is prepared.
Fig. 4 is the multi-functional self assemblies of GA-Fe@BSA-PTX that PTX, BSA, BSA@GA-Fe and embodiment 1 are prepared
The infrared absorption figure of body.
Fig. 5 is the relaxation rate fitted figure and relaxivity collection of illustrative plates of the multi-functional self-assemblies of GA-Fe@BSA-PTX.
Fig. 6 is the photo-thermal heating curve collection of illustrative plates of the GA-Fe@BSA-PTX nano-solutions of various concentration.
Fig. 7 is the thermograph of the GA-Fe@BSA-PTX nano-solutions of various concentration.
The tumour for the multi-functional self-assemblies of GA-Fe@BSA-PTX that Fig. 8 is GA-Fe@BSA and embodiment 1 is prepared
T1Weight MR imaging effects.
The mouse tail vein note for the multi-functional self-assemblies of GA-Fe@BSA-PTX that Fig. 9 is PBS and embodiment 1 is prepared
Penetrate photothermal imaging figure.
Specific implementation mode
A kind of preparation method of the multi-functional self-assemblies of GA-Fe@BSA-PTX, includes the following steps：
(1) bovine serum albumin is dissolved in secondary water, is added with stirring soluble trivalent iron salt, obtains mixed solution A；
(2) under stiring, gallic acid is added and is reacted into mixed solution A, purified after reaction, obtained pure
GA-Fe@BSA coordination polymer nano-particle aqueous solutions；
(3) GA-Fe@BSA coordination polymer nano-particle aqueous solutions are added in buffer solution, obtains mixed solution B, stirs
It mixes down, PTX solution reactions is added in mixed solution B, are purified after reaction, you can obtain GA-Fe@BSA-PTX and receive
Rice corpuscles solution, the GA-Fe@BSA-PTX nano-particles are the multi-functional self-assemblies of GA-Fe@BSA-PTX.
Preferably, in step (1), the mass concentration of bovine serum albumin is 0~3.0mg/mL in the mixed solution A,
But it is not 0.
Preferably, in step (1), the soluble trivalent iron salt is one kind of iron chloride, ferric nitrate or ferric sulfate, and
The mass concentration of soluble trivalent iron salt is 0~3.0g/mL in mixed solution A, but is not 0.
Preferably, in step (2), the mass concentration of gallic acid is 0~30.0mg/mL in mixed solution A.
Preferably, in step (3), the buffer solution be PBS solution, pH be 5~10, a concentration of 0~0.3mol/L,
But it is not 0.
Preferably, in step (3), the dispersion solvent of the PTX solution is ethyl alcohol, and feed postition is to be added dropwise, and is mixed
The mass concentration for closing PTX in solution B is 0~40.0 μ g/mL, but is not 0.
Preferably：
In step (2), reaction time 3-24h, reaction temperature is room temperature；
In step (3), the reaction time is 0~5h, but is not 0, and reaction temperature is room temperature.
Preferably：
In step (2), purification process is to be centrifuged after reaction, obtains sediment, is washed with water and washs precipitation
Object；
In step (3), purification process is to be centrifuged after reaction, obtains sediment, is washed with water and washs precipitation
Object.
The multi-functional self-assemblies of GA-Fe@BSA-PTX being prepared using the method, the self-assembly pass through use
BSA carries out modification regulation and control to GA-Fe and obtains extra small GA-Fe@BSA coordination polymerization nano-particles, recycles the hydrophobic assembling eggs of PTX
Extra small GA-Fe@BSA coordination polymerization nano-particles are assembled to obtain by the performance of white matter.
First, it is based on BSA and is rich in the ends N- and O- terminal amino acid residues, these sites and transition-metal Fe3+Have and matches by force
Position effect forms BSA-Fe by the way that soluble trivalent iron salt aqueous solution is added to BSA aqueous solutions3+Complex.Secondly, pass through to
BSA-Fe3+GA monomers are added in complex, the phenolic hydroxyl group and carboxyl in GA groups and Fe3+Chelating forms GA-Fe@BSA polycomplexations
Close nano-particle.Finally, using the performance of the hydrophobic assembling protein of taxol (PTX), extra small GA-Fe@BSA coordination polymerizations are received
Rice corpuscles assembles, and obtains GA-Fe@BSA-PTX nano-particles, the i.e. multi-functional self-assemblies of GA-Fe@BSA-PTX.
Preferably, the grain size about 100nm of the multi-functional self-assemblies of GA-Fe@BSA-PTX, single point spherical in shape of pattern
Dissipate nano particle.
The multi-functional self-assemblies of GA-Fe@BSA-PTX are controlled in mri contrast agent and/or photo-thermal-chemotherapy combined
Treat the application on drug.
The present invention is described in detail with specific embodiment below in conjunction with the accompanying drawings.
Embodiment 1
(1) 25mg bovine serum albumins are dissolved in 9mL secondary waters, are added with stirring soluble trivalent iron salt, are mixed
Solution A, in mixed solution A, the mass concentration of trivalent iron salt is 3.0g/mL.
(2) under stiring, gallic acid is added and is reacted into mixed solution A, in mixed solution A, the matter of gallic acid
Measure a concentration of 30.0mg/mL.React at room temperature 10h, after purify, purification step is：It is centrifuged, obtains after reaction
To sediment, it is washed with water and washs sediment.Finally, pure GA-Fe@BSA coordination polymer nano-particle aqueous solutions are obtained；
(3) it is 10 in pH, after GA-Fe@BSA aqueous solutions are added in the PBS buffer solutions of a concentration of 0.3mol/L, under stirring
PTX solution is added to react at room temperature, in mixed solution, PTX concentration of polymer solution is 30.0 μ g/mL, and dispersion solvent is ethyl alcohol, and is added
It is to be added dropwise to enter mode.5h is purified after reaction, and purification step is：It centrifuges, obtains sediment, be washed with water
Wash sediment.Finally, GA-Fe@BSA-PTX nano-particle solutions can be obtained, GA-Fe@BSA-PTX nano-particles are GA-Fe@
The multi-functional self-assemblies of BSA-PTX.
The composite structure schematic diagram of the multi-functional self-assemblies of above-mentioned GA-Fe@BSA-PTX is shown in Fig. 1.
Fig. 2 (a) and Fig. 2 (b) respectively illustrate the multi-functional self-assemblies of GA-Fe@BSA-PTX made from the present embodiment
TEM collection of illustrative plates and SEM figures.GA-Fe@BSA-PTX nano-particles dispersed nano particle spherical in shape known to from Fig. 2 (a) is average straight
Diameter is about 100nm.GA-Fe@BSA-PTX nano-particles dispersed nano particle spherical in shape known to from Fig. 2 (b), average diameter
About 100nm, it is consistent with Fig. 2 (a) results.
Fig. 3 shows the UV absorption figure for the multi-functional self-assemblies of GA-Fe@BSA-PTX that embodiment 1 is prepared, by
Fig. 3 is it is found that the GA-Fe@BSA-PTX nano-particles after assembling show to absorb more by force in the regions Vis-NIR, after illustrating assembling
GA-Fe@BSA-PTX nano-particles have good light thermal property.
Fig. 4 shows that the GA-Fe@BSA-PTX that PTX, BSA, BSA@GA-Fe and embodiment 1 are prepared are multi-functional certainly
The infrared absorption figure of assembly, is found, 1650cm by Fig. 4 comparative analyses-1The amide I band at place vibrates and in 1521cm-1Place
Amide II is with the absorption peak that vibration is BSA most features, it was demonstrated that contains BSA in GA-Fe@BSA nano-particles.BSA nanometers of GA-Fe@
Particle and GA-Fe@BSA-PTX nano-particles are in 615cm-1There is the amide of Fe-O absorption peaks and GA-Fe@BSA nano-particles
I bands are vibrated to be moved to lower wave number, it was demonstrated that Fe3+It is coordinated bonding with peptide bond O or N in BSA molecules or functional side chain group.Form GA-
After Fe@BSA nano-particles, in 3376cm-1And 3290cm-1The phenolic hydroxyl group O-H stretching vibration peaks at place and in 1031cm-1The carboxylic at place
The bending vibration of base O-H, which disappears, shows phenolic group in GA and carboxyl and Fe3+Chelating, thus illustrates, the GA-Fe@BSA of BSA regulation and control
Nano-particle successfully synthesizes.Taxol is a kind of lyophobic dust, and a large amount of ketone carbonyl hydrophobic groupings, analysis are contained in chemical constitution
The FT-IR spectrum of PTX, main feature absorption peak are 1733.8cm-1And 1714.4cm-1Ketone carbonyl C=O stretching vibrations at wave number
Peak, amide groups is in 1646.4cm-1Carbonyl peak at wave number, and in 3500cm-1The stretching vibration of hydroxyl O-H absorbs at wave number
Peak.Analyze the FT-IR spectrum of GA-Fe@BSA-PTX nano-particles, 1733.8cm-1And 1714.4cm-1Peak at wave number is opposite
The ketone carbonyl C=O stretching vibration peaks of PTX broaden, relative to 1650cm-1And 1521cm-1The amide of place BSA is vibrated to long wave side
To movement, illustrate that GA-Fe@BSA-PTX nano-particles assemble to be formed.
Fig. 5 is the relaxation rate fitted figure and relaxation for the multi-functional self-assemblies of GA-Fe@BSA-PTX that embodiment 1 is prepared
Efficiency collection of illustrative plates.It is found by Fig. 5 illustrations, with the increase of iron concentration, GA-Fe@BSA-PTX nano-particles are in aqueous solution
T1The trend gradually to brighten, and the T of maximum concentration nano material and blank control group water is presented in weighting MR imagings1Weight MR
Imaging shows apparent light and shade difference, illustrates that GA-Fe@BSA-PTX nano-particles have good T1Weight mr angiography ability.
Linear fit obtains longitudinal relaxation rate r1=1.95mM-1·s-1, transverse relaxation rate r2=1.20mM-1·s-1, r is calculated2/r1
=1.60<3.Compared with the GA-Fe@BSA nano-particles before assembling, longitudinal relaxation rate (r1=0.89mM-1·s-1) and laterally relax
Henan rate (r2=0.95mM-1·s-1) there are increase, the T of aqueous solution1Weighting mr angiography effect also enhances.
Fig. 6 shows the photo-thermal heating curve collection of illustrative plates of the GA-Fe@BSA-PTX nano-solutions of various concentration.It is found by Fig. 6,
The GA-Fe@BSA-PTX nano-solutions of various concentration are after laser irradiation, with the increase of concentration, the raised temperature of solution also by
Cumulative to add, when maximum concentration is 1mM, solution temperature can increase about 20 DEG C, show very strong photo-thermal effect.
Fig. 7 is the thermograph for the multi-functional self-assemblies of GA-Fe@BSA-PTX that embodiment 1 is prepared.By Fig. 7 solution
As a result, can more intuitively find, the concentration of the raised temperature of GA-Fe@BSA-PTX nano-solutions and solution is proportionate for thermal imaging.
Fig. 8 is the T of the tumour for the multi-functional self-assemblies of GA-Fe@BSA-PTX that embodiment 1 is prepared1Weight MR at
As effect.By Fig. 8 as a result, it has been found that, the GA-Fe BSA-PTX nano-particles and GA- of two groups of mouse intratumor injection isoconcentration equivalent
Fe BSA nano-particles, tumor locus pixel is both relative to brighter before injection material, and GA-Fe BSA-PTX nanoparticle subgroups
T1It is more preferable to weight MR imaging effects.
The mouse tail vein note for the multi-functional self-assemblies of GA-Fe@BSA-PTX that Fig. 9 is PBS and embodiment 1 is prepared
Penetrate photothermal imaging figure.It can be seen from the figure that the multi-functional self-assemblies of GA-Fe@BSA-PTX can play better photo-thermal therapy
Effect.
Therefore, the multi-functional self-assemblies of GA-Fe@BSA-PTX that embodiment 1 is prepared not only have good nuclear-magnetism total
The imaging effect to shake also while having the function of photo-thermal and chemotherapy double treatment, can be used as tumour integration reagent.
Embodiment 2
(1) 0.9mg bovine serum albumins are dissolved in 9mL secondary waters, are added with stirring soluble trivalent iron salt, are mixed
Solution A, in mixed solution A, the mass concentration of trivalent iron salt is 0.2g/mL.
(2) under stiring, gallic acid is added and is reacted into mixed solution A, in mixed solution A, the matter of gallic acid
Measure a concentration of 3.0mg/mL.React at room temperature 3h, after purify, purification step is：It is centrifuged, obtains after reaction
Sediment is washed with water and washs sediment.Finally, pure GA-Fe@BSA coordination polymer nano-particle aqueous solutions are obtained；
(3) after GA-Fe BSA aqueous solutions being added in the PBS buffer solutions that pH is 5, PTX solution room temperatures are added with stirring
It reacts, in mixed solution, PTX concentration of polymer solution is 2.0 μ g/mL, and dispersion solvent is ethyl alcohol, and feed postition is to add dropwise
Enter.0.5h is purified after reaction, and purification step is：It centrifuges, obtains sediment, be washed with water and wash sediment.Most
Afterwards, GA-Fe@BSA-PTX nano-particle solutions can be obtained, GA-Fe@BSA-PTX nano-particles are the more work(of GA-Fe@BSA-PTX
It can self-assembly.
Embodiment 3
(1) 2mg bovine serum albumins are dissolved in 9mL secondary waters, are added with stirring soluble trivalent iron salt, obtain mixing molten
Liquid A, in mixed solution A, the mass concentration of trivalent iron salt is 2g/mL.
(2) under stiring, gallic acid is added and is reacted into mixed solution A, in mixed solution A, the matter of gallic acid
Measure a concentration of 20.0mg/mL.React at room temperature 8h, after purify, purification step is：It is centrifuged, obtains after reaction
To sediment, it is washed with water and washs sediment.Finally, pure GA-Fe@BSA coordination polymer nano-particle aqueous solutions are obtained；
(3) after GA-Fe BSA aqueous solutions being added in the PBS buffer solutions that pH is 8, PTX solution room temperatures are added with stirring
It reacts, in mixed solution, PTX concentration of polymer solution is 20.0 μ g/mL, and dispersion solvent is ethyl alcohol, and feed postition is to add dropwise
Enter.4h is purified after reaction, and purification step is：It centrifuges, obtains sediment, be washed with water and wash sediment.Finally,
GA-Fe@BSA-PTX nano-particle solutions can be obtained, GA-Fe@BSA-PTX nano-particles are GA-Fe@BSA-PTX multi-functional
Self-assembly.
Embodiment 4
(1) 2.7mg bovine serum albumins are dissolved in 9mL secondary waters, are added with stirring soluble trivalent iron salt, are mixed
Solution A, in mixed solution A, the mass concentration of trivalent iron salt is 3.0g/mL.
(2) under stiring, gallic acid is added and is reacted into mixed solution A, in mixed solution A, the matter of gallic acid
Measure a concentration of 30.0mg/mL.Room temperature reaction for 24 hours, after purify, purification step is：It is centrifuged, obtains after reaction
To sediment, it is washed with water and washs sediment.Finally, pure GA-Fe@BSA coordination polymer nano-particle aqueous solutions are obtained；
(3) after GA-Fe BSA aqueous solutions being added in the PBS buffer solutions that pH is 10, PTX solution room temperatures are added with stirring
It reacts, in mixed solution, PTX concentration of polymer solution is 40.0 μ g/mL, and dispersion solvent is ethyl alcohol, and feed postition is to add dropwise
Enter.5h is purified after reaction, and purification step is：It centrifuges, obtains sediment, be washed with water and wash sediment.Finally,
GA-Fe@BSA-PTX nano-particle solutions can be obtained, GA-Fe@BSA-PTX nano-particles are GA-Fe@BSA-PTX multi-functional
Self-assembly.
The above-mentioned description to embodiment is for ease of ordinary skill in the art to understand and use the invention.It is ripe
The personnel for knowing art technology obviously easily can make various modifications to these embodiments, and general original described herein
It ought to use in other embodiment without having to go through creative labor.Therefore, the present invention is not limited to the above embodiments, this field
Technical staff's announcement according to the present invention, improvement and modification made without departing from the scope of the present invention all should be in the guarantors of the present invention
Within the scope of shield.
Claims (10)
1. a kind of preparation method of the multi-functional self-assemblies of GA-Fe@BSA-PTX, which is characterized in that include the following steps：
(1) bovine serum albumin is dissolved in secondary water, is added with stirring soluble trivalent iron salt, obtains mixed solution A；
(2) under stiring, gallic acid is added and is reacted into mixed solution A, purified after reaction, obtain pure GA-
Fe@BSA coordination polymer nano-particle aqueous solutions；
(3) GA-Fe@BSA coordination polymer nano-particle aqueous solutions are added in buffer solution, obtain mixed solution B, stir
Under, PTX solution reactions are added in mixed solution B, are purified after reaction, you can obtain BSA-PTX nanometers of GA-Fe@
Particle solution, the GA-Fe@BSA-PTX nano-particles are the multi-functional self-assemblies of GA-Fe@BSA-PTX.
2. a kind of preparation method of the multi-functional self-assemblies of GA-Fe@BSA-PTX according to claim 1, feature exist
In in step (1), the mass concentration of bovine serum albumin is 0~3.0mg/mL in the mixed solution A, but is not 0.
3. a kind of preparation method of the multi-functional self-assemblies of GA-Fe@BSA-PTX according to claim 1, feature exist
In in step (1), the soluble trivalent iron salt is one kind of iron chloride, ferric nitrate or ferric sulfate, and in mixed solution A
The mass concentration of soluble trivalent iron salt is 0~3.0g/mL, but is not 0.
4. a kind of preparation method of the multi-functional self-assemblies of GA-Fe@BSA-PTX according to claim 1, feature exist
In in step (2), the mass concentration of gallic acid is 0~30.0mg/mL in mixed solution A.
5. a kind of preparation method of the multi-functional self-assemblies of GA-Fe@BSA-PTX according to claim 1, feature exist
In in step (3), the buffer solution is PBS solution, and pH is 5~10, a concentration of 0~0.3mol/L, but is not 0.
6. a kind of preparation method of the multi-functional self-assemblies of GA-Fe@BSA-PTX according to claim 1, feature exist
In in step (3), the dispersion solvent of the PTX solution is ethyl alcohol, and feed postition is to be added dropwise, PTX in mixed solution B
Mass concentration be 0~40.0 μ g/mL, but be 0.
7. a kind of preparation method of the multi-functional self-assemblies of GA-Fe@BSA-PTX according to claim 1, feature exist
In：
In step (2), reaction time 3-24h, reaction temperature is room temperature；
In step (3), the reaction time is 0~5h, but is not 0, and reaction temperature is room temperature.
8. a kind of preparation method of the multi-functional self-assemblies of GA-Fe@BSA-PTX according to claim 1, feature exist
In：
In step (2), purification process is to be centrifuged after reaction, obtains sediment, is washed with water and washs sediment；
In step (3), purification process is to be centrifuged after reaction, obtains sediment, is washed with water and washs sediment.
9. the multi-functional self-assemblies of GA-Fe@BSA-PTX being prepared using the method as described in claim 1~8 is any,
It is characterized in that, the self-assembly obtains extra small GA-Fe@BSA coordination polymerizations by carrying out modification regulation and control to GA-Fe with BSA
Nano-particle recycles the performance of the hydrophobic assembling protein of PTX, extra small GA-Fe@BSA coordination polymerization nano-particles is assembled
It obtains.
10. the multi-functional self-assemblies of GA-Fe@BSA-PTX as claimed in claim 11 are in mri contrast agent and/or light
Application on heat-chemotherapy combined medicine.
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