CN105327354A - Preparing method for tobacco mosaic virus nanowire composite material with surface functionalized - Google Patents
Preparing method for tobacco mosaic virus nanowire composite material with surface functionalized Download PDFInfo
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Abstract
The invention discloses a preparing method for a tobacco mosaic virus nanowire composite material with the surface functionalized. The preparing method includes the following steps that while tobacco mosaic virus head-tail assembly is carried out on the acidic condition, dopamine and an oxidant are subjected to in-situ oxidative polymerization on the outer surface of virus protein to form tobacco mosaic virus nanowires coated with polydopamine, and on the alkaline condition, the own reducibility and reactivity of the surface polydopamine are used for further loading gold nanoparticles and modifying bioactive molecules containing amino groups or sulfydryl groups in a functionalized mode without extra reductant or chemical modification so as to obtain the tobacco mosaic virus nanowire composite material with the surface functionalized. The preparing method has the advantages of being simple in process, convenient, efficient and capable of being widely applied to biological catalysis, biological imaging, tumor targeted probes, nano-drug carriers and other fields of biomedical new nano materials.
Description
Technical field
The present invention relates to nanometer field of new.More specifically, a kind of preparation method of surface-functionalized tobacco mosaic virus (TMV) nanowire composite is related to.
Background technology
Nano composite material is the novel nano material of a class, both there is the advantages such as the small-size effect of nano material, high-specific surface area, diversified shape characteristic and assembling form, again can compound other are inorganic, organic, the property of macromolecule and Biofunctional materials, in industrial high-efficient catalysis, the new function material fields such as bio-medical engineering obtain to be developed widely.Therefore the one-dimensional nano line composite of development of new has very huge potential using value in living things catalysis, bio-imaging, cancer target probe and nano-medicament carrier.
Poly-dopamine is formed by dopamine oxidation polymerization under alkaline environment, is a kind of novel organic polymer adhesion material, can be coated on substrate surface uniformly, and can contain the molecule of amino or sulfydryl by functional modification further at material surface.And existing technology mainly carries out the coated of poly-dopamine and functional modification at inorganic metal, metal-oxide, pottery, hydrophobic macromolecular material and carbon material surface.What such as, propose in US Patent No. 2008/0149566 is coated at multiple inorganic and poly-dopamine that is polymer surface; Chinese patent CN102813963 and CN102000658 has bioactive molecule in inorganic, the poly-Dopamineization modification of metal, metal alloy and polymer surface of bio-medical; Chinese patent CN104258909 is at the poly-dopamine load gold nano grain of magnetic Fe_3O_4 nano grain surface; Chinese patent CN104666251 is at the poly-dopamine load hydrophobic drug in biodegradable biopolymer nanoparticles surface; Chinese patent CN103920152 and CN104549159 is that the one-dimensional inorganic nano material Surface coating being representative at multi-walled carbon nano-tubes and magnetic nano silver wire gathers dopamine.But these technical methods all do not relate at hydrophilic protein surface or the coated and further functional modification being carried out poly-dopamine by the virus type biological nano particle surface of protein assembly.
Tobacco mosaic virus (TMV) is a kind of plant virus infecting Nicotiana tabacum L. and other Solanaceae classes, assembled by 2130 virus capsid proteins and form 300nm length, the nano tubular structure of diameter 18nm, has the single dispersing characteristic of homogeneous grain diameter, is a kind of desirable biological template constructing monodimension nanometer material.Take tobacco mosaic virus (TMV) as template, the mode of being assembled end to end by virus nanoparticles forms the orderly nano thread structure of one dimension, and the polyaniline of Surface coating electric conductivity outside, polypyrrole and kayexalate macromolecular material, the one-dimensional nano line composite that preparation has conducting function has had bibliographical information (such as Z.Niu, M.Bruckman, etal.Studyandcharacterizationoftobaccomosaicvirushead-to-tailassemblyassistedbyanilinepolymerization [J] .Chem.Commun., 2006, 28:3019, Z.Niu, etal.Assemblyoftobaccomosaicvirusintofibrousandmacroscop icbundledarraysmediatedbysurfaceanilinepolymerization [J] .Langmuir, 2007,23:6719, Z.Niu, etal.Biologicaltemplatedsynthesisofwater-solubleconducti vepolymericnanowires [J] .Nanoletters, 2007,7:3729).But the clad material that existing method uses is all the macromolecule of electric conductivity, does not have biocompatibility, cannot be applied at biomedical sector.
In addition, take tobacco mosaic virus (TMV) as template and carrier, although realize in the method for its area load gold nano grain and functional modification molecule that (such as Chinese patent CN103706800 reaches by molecular biological method table the coat protein for mosaic virus of tobacco that six histidine modify, then adds the load of gold nano grain on tobacco mosaic virus (TMV) surface that reducing agent realizes; Chinese patent CN102578695 is attracted each other by electrostatic, with the method for chemical deposition at tobacco mosaic virus (TMV) area load gold nano grain under the effect of reducing agent; Chinese patent CN103613647 is the coat protein for mosaic virus of tobacco being reached cysteine mutation by molecular biological method table, then protein surface fluorescence molecule and cancer therapy drug being modified cysteine mutation has prepared nano-medicament carrier), but all there is operating procedure complexity in these methods, manufacturing cycle is long, need molecular biological method to revise gene order and expressing protein, need to add reducing agent reduction in addition and obtain the problems such as gold nano grain and defect.
Up to now, using the poly-dopamine with biocompatibility to carry out coated, is that the preparation method of the one-dimensional nano line composite that template assemblies is formed also was not reported with tobacco mosaic virus (TMV); Simultaneously in this tobacco mosaic virus (TMV) nanowire surface, utilize reproducibility and the reactivity of poly-dopamine self, without the need to extra reducing agent and molecular biology method, just can further facilitate the method that load gold nano grain and functional modification efficiently have a bioactive molecule and also have no report.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of surface-functionalized tobacco mosaic virus (TMV) nanowire composite.This preparation method operating procedure is simple, and manufacturing cycle is short, uses the poly-dopamine with biocompatibility to carry out coated, take tobacco mosaic virus (TMV) as the one-dimensional nano line composite that template assemblies is formed; Simultaneously in this tobacco mosaic virus (TMV) nanowire surface, utilize reproducibility and the reactivity of poly-dopamine self, without the need to extra reducing agent and molecular biology method, just can further facilitate efficiently that load gold nano grain and functional modification have bioactive molecule.
For achieving the above object, the present invention adopts following technical proposals:
A kind of preparation method of surface-functionalized tobacco mosaic virus (TMV) nanowire composite, comprise following preparation process: first carry out the assembling that Surface coating gathers the tobacco mosaic virus (TMV) nano wire of dopamine, in recycling gained nanowire surface, coated poly-dopamine carries out functional modification, obtains surface-functionalized tobacco mosaic virus (TMV) nanowire composite.
Preferably, the assembling that described Surface coating gathers the tobacco mosaic virus (TMV) nano wire of dopamine refers to and add dopamine hydrochloride and oxidant in acidic buffer solution, by the method for in-situ oxidizing-polymerizing while tobacco mosaic virus (TMV) Surface Creation gathers dopamine clad, be that template assembles the nano wire forming one dimension by mode from beginning to end with tobacco mosaic virus (TMV), and poly-dopamine clad is fixed and is maintained the 1-dimention nano line structure formed, and specifically comprises the steps:
1) tobacco mosaic virus (TMV) is evenly spread in acidic buffer solution, forming reactions solution, and stir;
2) to step 1) add dopamine hydrochloride and oxidant in gained reaction solution, after abundant stirring reaction, the alkaline solution adjust ph adding 100mM is continue reaction 0.5 ~ 2 hour after 7.4 ~ 8.5;
3) by step 2) gained reaction solution is centrifugal, gets the supernatant, obtains the tobacco mosaic virus (TMV) nano wire that Surface coating gathers dopamine after dialysis, lyophilization.
Preferably, step 1) in, the mass concentration of described reaction solution is 0.1 ~ 2.0mg/mL, and described mixing time is 0.5 ~ 4 hour; Step 2) in, described stirring reaction to refer under 4 ~ 35 DEG C of conditions abundant stirring reaction 2 ~ 8 hours; Step 3) in, described centrifugal rotating speed is 5000 ~ 10000rpm, and centrifugation time is 5 ~ 10min, and it is that 10 ~ 1,000,000 daltonian bag filters are dialysed 24 ~ 48 hours in pure water that described dialysis refers to molecular cut off.
Preferably, step 1) in, described acidic buffer solution is sodium acetate buffer solution, sodium citrate buffer or the middle one of phosphate buffered solution (PBS); The pH value of described acidic buffer solution is 4.5 ~ 6.8, and molar concentration is 50 ~ 100mM.
Preferably, step 2) in, described oxidant is Ammonium persulfate., the one in hydrogen peroxide or oxygen; Described alkaline solution is sodium hydrate aqueous solution or Tris aqueous solution (Tris aqueous solution); The mass ratio of described dopamine hydrochloride and tobacco mosaic virus (TMV) is 0.2:1 ~ 2:1, and the molar concentration rate of dopamine hydrochloride and oxidant is 1:2 ~ 1:4.
Preferably, step 3) in, described Surface coating gathers the tobacco mosaic virus (TMV) nano wire of dopamine, and its diameter is 18 ~ 40nm, and length is 300nm ~ 20 μm, and the thickness of poly-dopamine clad is 1 ~ 10nm.
Preferably, describedly poly-dopamine coated in gained nanowire surface is utilized to carry out functional modification, refer to and gather the tobacco mosaic virus (TMV) nano wire of dopamine for template with Surface coating, in alkaline buffer solution, poly-dopamine clad absorption and the solution of reduction containing gold ion, thus realize the growth of gold nano grain on one-dimensional nano line surface; Or poly-dopamine clad reacts with the bioactive molecule that has containing amino or sulfydryl, thus practical function molecule is in the modification on one-dimensional nano line surface, finally obtain described surface-functionalized tobacco mosaic virus (TMV) nanowire composite, specifically comprise the steps:
A. tobacco mosaic virus (TMV) nano wire Surface coating being gathered dopamine evenly spreads in alkaline buffer solution, forming reactions solution, and stirs;
B. in reaction solution described in step a, add the solution containing gold ion, or add, containing amino or sulfydryl, there is bioactive molecule, after reacting completely, through dialysis, lyophilization, obtain surface-functionalized tobacco mosaic virus (TMV) nanowire composite.
Preferably, in step a, the mass concentration of described reaction solution is 0.1 ~ 2.0mg/mL, and described mixing time is 0.5 ~ 2 hour; In step b, described in react completely refer under 4 DEG C of conditions react 2 ~ 24 hours, it is that 10 ~ 1,000,000 daltonian bag filters are dialysed 24 ~ 48 hours in pure water that described dialysis refers to molecular cut off.
Preferably, in step a, described alkaline buffer solution is Tris buffer solution (Tris-HCl buffer), the one in phosphate buffered solution (PBS) or sodium carbonate-bicarbonate buffer; Described alkaline buffer solution pH value is 7.8 ~ 8.5, and molar concentration is 10 ~ 100mM.
Preferably, in step b, the described solution containing gold ion is aqueous solution of chloraurate, and its mass concentration is 0.01 ~ 10mg/mL; Described is cancer therapy drug doxorubicin hydrochloride (DOX) or tumor targeted molecular ring-type arginine-glycine-aspartic acid polypeptide (cRGD ring type polypeptide) containing the bioactive molecule that has that is amino or sulfydryl, and described is 1 ~ 20mg/mL containing the bioactive molecular mass concentration that has that is amino or sulfydryl.
Beneficial effect of the present invention is as follows:
(1) poly-dopamine is solved in hydrophilic protein or the coated problem of surfaces of viral particles, positively charged by the dopamine under sour environment, easily be adsorbed on the protein surface of surface band negative charge, add the oxidant in-situ oxidizing-polymerizing dopamine such as Ammonium persulfate. simultaneously and generate poly-dopamine, thus make hydrophilic protein or the coated strata dopamine of tobacco mosaic virus (TMV) intimate surface, after reaction completes substantially, adjust ph is to neutral or alkalescence again, and the poly-dopamine of solidification is coated further.This is obviously different from the polymeric reaction condition of dopamine directly under alkaline environment described by art methods.
(2) instead of conductive polymer material with the poly-dopamine with biocompatibility, solving the conventional polymer materials such as polyaniline cannot in the shortcoming of biomedical sector application, and the one-dimensional nano line making the surface prepared gather the coated tobacco mosaic virus (TMV) assembling of dopamine has potential biomedical applications and is worth.
(3) make use of poly-dopamine and can adsorb the ability with reducing metal ion under alkaline environment, without the need to adding extra reducing agent, can at the coated tobacco mosaic virus (TMV) Surface Creation gold nano grain of poly-dopamine, solve traditional method to need to add reducing agent, need the shortcoming of Tobacco mosaic virus being carried out to molecular biological genetic modification, sudden change and expression, greatly simplify preparation method, shorten manufacturing cycle, technique is simple, convenience and high-efficiency.
(4) make use of the ability that poly-dopamine can carry out with the molecule containing amino or sulfydryl reacting under alkaline environment, without the need to extra chemical modification and modified method, can at the coated tobacco mosaic virus (TMV) finishing functional molecular of poly-dopamine.Such as, in the present invention cancer therapy drug doxorubicin hydrochloride DOX and tumor targeted molecular cRGD ring type polypeptide are just directly modified the tobacco mosaic virus (TMV) nanowire surface arriving one dimension by simple mix and blend, solve traditional method and need extra chemical reaction, the more shortcoming easily making protein denaturation precipitation of intermediate steps; Or need to carry out molecular biological genetic modification, sudden change and expression to produce the shortcoming of reactive groups to Tobacco mosaic virus.
(5) the tobacco mosaic virus (TMV) nanowire composite that gained of the present invention is surface-functionalized can be applicable to the fields such as living things catalysis, bio-imaging, cancer target probe and nano-medicament carrier.
Accompanying drawing explanation
Below in conjunction with accompanying drawing, the specific embodiment of the present invention is described in further detail.
Fig. 1 illustrates the reaction process schematic diagram of a kind of surface-functionalized tobacco mosaic virus (TMV) nanowire composite preparation method of the embodiment of the present invention.
Fig. 2 illustrates the transmission electron microscope picture of the one-dimensional nano line composite prepared by the embodiment of the present invention 1.
Fig. 3 illustrates the scanning electron microscope (SEM) photograph of the one-dimensional nano line composite prepared by the embodiment of the present invention 1.
Fig. 4 illustrates the dynamic light scattering figure of the one-dimensional nano line composite prepared by the embodiment of the present invention 1.
Fig. 5 illustrates ultraviolet-visible spectrogram and the calibration curve (Fig. 5 (a)) of the one-dimensional nano line composite prepared by the embodiment of the present invention 2, and ultraviolet absorption value at 314nm and 480nm place over time (Fig. 5 (b)).
Fig. 6 (a) (b) (c) illustrates in the embodiment of the present invention 1 transmission electron microscope picture of gold nano grain composite adding 5 μ L, 20 μ L, one-dimensional nano line area load different size prepared by 100 μ L chlorauric acid solutions respectively.
Fig. 7 illustrates the transmission electron microscope picture of one-dimensional nano line finishing cancer therapy drug doxorubicin hydrochloride prepared by the embodiment of the present invention 8 and tumor targeted molecular cRGD ring type polypeptide composite.
Detailed description of the invention
In order to be illustrated more clearly in the present invention, below in conjunction with preferred embodiments and drawings, the present invention is described further.Parts similar in accompanying drawing represent with identical Reference numeral.It will be appreciated by those skilled in the art that specifically described content is illustrative and nonrestrictive, should not limit the scope of the invention with this below.
The reaction process schematic diagram of a kind of surface-functionalized tobacco mosaic virus (TMV) nanowire composite preparation method provided by the invention, as shown in Figure 1.
Embodiment 1
The tobacco mosaic virus (TMV) of 1mg being distributed to pH value is in the sodium acetate buffer solution 2mL of the 100mM of 5.5, be made into the reaction solution that mass concentration is 0.5mg/mL, stir under 4 DEG C of conditions after 2 hours, the dopamine hydrochloride of 1mg and the Ammonium persulfate. of 2.4mg is added in reaction solution, under 25 DEG C of conditions, abundant stirring reaction is after 4 hours, add the sodium hydrate aqueous solution 50uL of 100mM several times, simultaneously with the wide model pH reagent paper monitoring of 1-14 scope, reacting solution pH value is regulated to be 8.5 rear continuation reaction 2 hours, then by reaction solution centrifugal 10min under the rotating speed of 9500rpm, get the supernatant, be that 1,000,000 daltonian bag filters are dialysed 48 hours in pure water with molecular cut off, within every 8 hours, change 1 st pure water, last lyophilization obtains the tobacco mosaic virus (TMV) nano wire that Surface coating gathers dopamine.
The pH value that the tobacco mosaic virus (TMV) nano wire Surface coating of above-mentioned for 1mg preparation being gathered dopamine is dispersed in 10mM is in the Tris buffer solution 2mL of 8.5, forming mass concentration is the reaction solution of 0.5mg/mL, stir 0.5 hour, add 10mg/mL aqueous solution of chloraurate 5 respectively, 20, 100 μ L, under 4 DEG C of conditions, mixing is rear rapidly reacts 24 hours, be that 1,000,000 daltonian bag filters are dialysed 48 hours in pure water with molecular cut off, within every 8 hours, change 1 st pure water, last lyophilization can obtain the one dimension tobacco mosaic virus (TMV) nanowire composite of gold nano grain at area load of different size.
Surface coating prepared by the present embodiment gathers transmission electron microscope picture and the scanning electron microscope (SEM) photograph of the tobacco mosaic virus (TMV) nano wire of dopamine, as shown in Figures 2 and 3, the diameter demonstrating the tobacco mosaic virus (TMV) nano wire of this one dimension is 22 ~ 26nm, length is 2 ~ 20 μm, and the thickness of poly-dopamine clad is 4 ~ 8nm.The dynamic light scattering figure of the tobacco mosaic virus (TMV) nano wire of this one dimension prepared by the present embodiment, as shown in Figure 4, the hydration radius having neither part nor lot in the tobacco mosaic virus (TMV) forming nano wire is 89.4nm, the hydration radius participating in the tobacco mosaic virus (TMV) forming nano wire is 721.8nm, considerably beyond the hydration radius of tobacco mosaic virus (TMV) itself, further demonstrate the set of nanowires assembling structure that it is one dimension in the solution.
The gold nano grain of the different sizes prepared by the present embodiment the one dimension tobacco mosaic virus (TMV) nanowire composite of area load transmission electron microscope picture as shown in Figure 6, the gold nano grain of generation distributes at the surface uniform of one-dimensional nano line composite.Fig. 6 (a) is for adding 5 μ L gold chloride reactions, and the gold nano grain diameter of generation is at 2 ~ 5nm; Fig. 6 (b) is for adding 20 μ L gold chloride reactions, and the gold nano grain diameter of generation is at 10 ~ 30nm; Fig. 6 (c) is for adding 100 μ L gold chloride reactions, and the gold nano grain diameter of generation is at 200 ~ 300nm.The present embodiment shows that the addition of gold chloride can affect the size of nanometer gold grain of generation significantly.
Embodiment 2
The tobacco mosaic virus (TMV) of 1mg being distributed to pH value is in the sodium acetate buffer solution 2mL of the 100mM of 5.5, be made into the reaction solution that mass concentration is 0.5mg/mL, stir under 4 DEG C of conditions after 2 hours, the dopamine hydrochloride of 1mg and the Ammonium persulfate. of 2.4mg is added in reaction solution, abundant stirring reaction 24 hours under 25 DEG C of conditions, temporally puts sampling and testing ultraviolet-visible spectrum absorption value.Then by reaction solution centrifugal 10min under the rotating speed of 9500rpm, get the supernatant, be that 1,000,000 daltonian bag filters are dialysed 48 hours in pure water with molecular cut off, within every 8 hours, change 1 st pure water, lyophilization.
Surface coating prepared by the present embodiment gathers the ultraviolet-visible absorption spectroscopy of the sampling in time figure of the tobacco mosaic virus (TMV) nano wire of dopamine as shown in Fig. 5 (a), its ultraviolet absorption value at 314nm and 480nm place linearly increases trend as shown in Fig. 5 (b) to time mapping, and the reaction indicating dopamine oxidation polymerization in acid condition increases gradually.
Embodiment 3
The tobacco mosaic virus (TMV) of 1mg being distributed to pH value is in the sodium acetate buffer solution 2mL of the 100mM of 5.5, be made into the reaction solution that mass concentration is 0.5mg/mL, stir under 4 DEG C of conditions after 2 hours, 0.2 is added respectively in reaction solution, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4, 1.6, 1.8, the dopamine hydrochloride of 2.0mg and molar concentration rate are the Ammonium persulfate. 0.48 ~ 4.8mg of 1:2, under 25 DEG C of conditions, abundant stirring reaction is after 4 hours, add the sodium hydrate aqueous solution 50uL of 100mM several times, simultaneously with the wide model pH reagent paper monitoring of 1-14 scope, reacting solution pH value is regulated to be 8.5 rear continuation reaction 2 hours, then by reaction solution centrifugal 10min under the rotating speed of 9500rpm, get the supernatant, be that 1,000,000 daltonian bag filters are dialysed 48 hours in pure water with molecular cut off, within every 8 hours, change 1 st pure water, last lyophilization obtains Surface coating has different-thickness to gather the tobacco mosaic virus (TMV) nano wire of dopamine.
The present embodiment carries out the coated experiment of tobacco mosaic virus (TMV) nano wire by the dopamine hydrochloride adding different proportion, optimum when the mass ratio showing dopamine hydrochloride and the tobacco mosaic virus (TMV) added is 1:1.
Embodiment 4
The tobacco mosaic virus (TMV) of 1mg being distributed to respectively pH value is 4.5, 5.5, the sodium acetate buffer solution of the 50mM of 6.0, pH value is 6.8, the phosphate buffered solution of the 50mM of 7.4, pH value is in the Tris buffer solution (Tris-HCl buffer) of the 50mM of 8.5, be made into the reaction solution that mass concentration is 0.5mg/mL, stir under 4 DEG C of conditions after 2 hours, the dopamine hydrochloride of 1mg and the Ammonium persulfate. of 2.4mg is added in reaction solution, under 25 DEG C of conditions, abundant stirring reaction is after 4 hours, add the sodium hydrate aqueous solution 50uL of 100mM several times, simultaneously with the wide model pH reagent paper monitoring of 1-14 scope, reacting solution pH value is regulated to be 8.5 rear continuation reaction 2 hours, then by reaction solution centrifugal 10min under the rotating speed of 9500rpm, get the supernatant, be that 1,000,000 daltonian bag filters are dialysed 48 hours in pure water with molecular cut off, within every 8 hours, change 1 st pure water, lyophilization.
The present embodiment carries out the coated experiment of tobacco mosaic virus (TMV) nano wire by the buffer solution adding different pH value, shows that solution ph is higher, and the response speed of dopamine polymerization is faster, but covered effect is also poorer simultaneously.It is the tobacco mosaic virus (TMV) nano wire optimum prepared in the sodium acetate buffer solution of 5.5 at pH value.
Embodiment 5
The tobacco mosaic virus (TMV) of 1mg being distributed to pH value is in the sodium acetate buffer solution 2mL of the 100mM of 5.5, be made into the reaction solution that mass concentration is 0.5mg/mL, stir under 4 DEG C of conditions after 2 hours, the dopamine hydrochloride and 2.4 of 1mg is added respectively in reaction solution, 3.6, (molar concentration rate is 1:2 to 4.8mg, 1:3, Ammonium persulfate. 1:4), under 25 DEG C of conditions, abundant stirring reaction is after 4 hours, add the sodium hydrate aqueous solution 50uL of 100mM several times, simultaneously with the wide model pH reagent paper monitoring of 1-14 scope, reacting solution pH value is regulated to be 8.5 rear continuation reaction 2 hours, then by reaction solution centrifugal 10min under the rotating speed of 9500rpm, get the supernatant, be that 1,000,000 daltonian bag filters are dialysed 48 hours in pure water with molecular cut off, within every 8 hours, change 1 st pure water, lyophilization.
The present embodiment carries out the coated experiment of tobacco mosaic virus (TMV) nano wire by the ammonium persulfate oxidizing agent adding different proportion, shows that excessive oxidant can accelerate the polymerization rate of dopamine but covered effect is poor simultaneously.It is optimum when the molar concentration rate of dopamine hydrochloride and Ammonium persulfate. is 1:2.
Embodiment 6
The tobacco mosaic virus (TMV) of 1mg being distributed to pH value is in the sodium citrate buffer 2mL of the 50mM of 4.5, be made into the reaction solution that mass concentration is 0.1mg/mL, stir under 4 DEG C of conditions after 4 hours, the dopamine hydrochloride of 0.2mg is added in reaction solution, and continue to pass into bubble oxygen, under 35 DEG C of conditions, abundant stirring reaction is after 8 hours, add the Tris aqueous solution 50uL of 100mM several times, simultaneously with the wide model pH reagent paper monitoring of 1-14 scope, reacting solution pH value is regulated to be 7.4 rear continuation reaction 0.5 hour, then by reaction solution centrifugal 5min under the rotating speed of 10000rpm, get the supernatant, be that 100,000 daltonian bag filters are dialysed 24 hours in pure water with molecular cut off, within every 8 hours, change 1 st pure water, last lyophilization obtains the tobacco mosaic virus (TMV) nano wire that Surface coating gathers dopamine.
The pH value that the tobacco mosaic virus (TMV) nano wire Surface coating of above-mentioned for 1mg preparation being gathered dopamine is dispersed in 100mM is in the phosphate buffered solution of 7.8, forming mass concentration is the reaction solution of 2.0mg/mL, stir 2 hours, add the cancer therapy drug doxorubicin hydrochloride (DOX) that mass concentration is 20mg/mL, react after 2 hours with the centrifugal 5min of the rotating speed of 9500rpm under 4 DEG C of conditions, get the supernatant, be that 100,000 daltonian bag filters are dialysed 24 hours in pure water with molecular cut off, within every 8 hours, change a water, last lyophilization obtains the one dimension tobacco mosaic virus (TMV) nanowire composite of finishing cancer therapy drug doxorubicin hydrochloride DOX.
Embodiment 7
The tobacco mosaic virus (TMV) of 1mg being distributed to pH value is in the phosphate buffered solution 2mL of the 100mM of 6.8, be made into the reaction solution that mass concentration is 2.0mg/mL, stir under 4 DEG C of conditions after 0.5 hour, dopamine hydrochloride and the Ammonium persulfate. of 2mg is added in reaction solution, the molar concentration rate of dopamine and Ammonium persulfate. is 1:4, under 4 DEG C of conditions, abundant stirring reaction is after 2 hours, add the sodium hydrate aqueous solution 50uL of 100mM several times, simultaneously with the wide model pH reagent paper monitoring of 1-14 scope, reacting solution pH value is regulated to be 8.5 rear continuation reaction 2 hours, then by reaction solution centrifugal 10min under the rotating speed of 5000rpm, get the supernatant, be that 1,000,000 daltonian bag filters are dialysed 48 hours in pure water with molecular cut off, within every 8 hours, change 1 st pure water, last lyophilization obtains the tobacco mosaic virus (TMV) nano wire that Surface coating gathers dopamine.
The pH value that the tobacco mosaic virus (TMV) nano wire Surface coating of above-mentioned for 1mg preparation being gathered dopamine is dispersed in 10mM is in the Tris buffer solution of 8.5, forming mass concentration is the reaction solution of 0.5mg/mL, add 10mg tumor targeted molecular ring-type arginine-glycine-aspartic acid polypeptide, react after 2 hours with the centrifugal 5min of the rotating speed of 9500rpm under 4 DEG C of conditions, get the supernatant, be that 1,000,000 daltonian bag filters are dialysed 24 hours in pure water with molecular cut off, within every 8 hours, change 1 st pure water, last lyophilization obtains the one-dimensional nano line composite of finishing tumor targeted molecular cRGD ring type polypeptide.
Embodiment 8
The pH value that tobacco mosaic virus (TMV) nano wire Surface coating prepared by 1mg above-described embodiment 1 being gathered dopamine is dispersed in 10mM is in the Tris buffer solution of 8.5, forming mass concentration is the reaction solution of 0.5mg/mL, add 5mg cancer therapy drug doxorubicin hydrochloride (DOX) and 5mg tumor targeted molecular cRGD ring type polypeptide successively, react under 4 DEG C of conditions after 4 hours, with the centrifugal 5min of the rotating speed of 9500rpm, get the supernatant, be that 1,000,000 daltonian bag filters are dialysed 24 hours in pure water with molecular cut off, within every 8 hours, change 1 st pure water, the one-dimensional nano line composite that difunctionalization that last lyophilization obtains area load cancer therapy drug doxorubicin hydrochloride (DOX) and tumor targeted molecular cRGD ring type polypeptide is modified.
The transmission electron microscope picture of the one-dimensional nano line composite that the cancer therapy drug prepared by the present embodiment and targeted molecular difunctionalization are modified as shown in Figure 7, can also keep the set of nanowires assembling structure of its one dimension through the composite of difunctionalization modification.
Obviously; the above embodiment of the present invention is only for example of the present invention is clearly described; and be not the restriction to embodiments of the present invention; for those of ordinary skill in the field; can also make other changes in different forms on the basis of the above description; here cannot give exhaustive to all embodiments, every belong to technical scheme of the present invention the apparent change of extending out or variation be still in the row of protection scope of the present invention.
Claims (10)
1. the preparation method of a surface-functionalized tobacco mosaic virus (TMV) nanowire composite, it is characterized in that: comprise the steps: first to carry out the assembling that Surface coating gathers the tobacco mosaic virus (TMV) nano wire of dopamine, in recycling gained nanowire surface, coated poly-dopamine carries out functional modification, obtains surface-functionalized tobacco mosaic virus (TMV) nanowire composite.
2. basis
claimpreparation method described in 1, is characterized in that: the number of assembling steps that described Surface coating gathers the tobacco mosaic virus (TMV) nano wire of dopamine is as follows:
1) tobacco mosaic virus (TMV) is evenly spread in acidic buffer solution, forming reactions solution, and stir;
2) to step 1) add dopamine hydrochloride and oxidant in gained reaction solution, after abundant stirring reaction, the alkaline solution adjust ph adding 100mM is continue reaction 0.5 ~ 2 hour after 7.4 ~ 8.5;
3) by step 2) gained reaction solution is centrifugal, gets the supernatant, obtains the tobacco mosaic virus (TMV) nano wire that Surface coating gathers dopamine after dialysis, lyophilization.
3. basis
claimpreparation method described in 2, is characterized in that: step 1) in, the mass concentration of described reaction solution is 0.1 ~ 2.0mg/mL, and described mixing time is 0.5 ~ 4 hour; Step 2) in, described stirring reaction to refer under 4 ~ 35 DEG C of conditions abundant stirring reaction 2 ~ 8 hours; Step 3) in, described centrifugal rotating speed is 5000 ~ 10000rpm, and centrifugation time is 5 ~ 10min, and it is that 10 ~ 1,000,000 daltonian bag filters are dialysed 24 ~ 48 hours in pure water that described dialysis refers to molecular cut off.
4.
according to claimpreparation method described in 2, is characterized in that: step 1) in, described acidic buffer solution is sodium acetate buffer solution, a kind of in sodium citrate buffer or phosphate buffered solution; The pH value of described acidic buffer solution is 4.5 ~ 6.8, and molar concentration is 50 ~ 100mM.
5.
according to claimpreparation method described in 2, is characterized in that: step 2) in, described oxidant is Ammonium persulfate., the one in hydrogen peroxide or oxygen; Described alkaline solution is sodium hydrate aqueous solution or Tris aqueous solution; The mass ratio of described dopamine hydrochloride and tobacco mosaic virus (TMV) is 0.2:1 ~ 2:1, and the molar concentration rate of dopamine hydrochloride and oxidant is 1:2 ~ 1:4.
6. basis
claimpreparation method described in 2, is characterized in that: step 3) in, described Surface coating gathers the tobacco mosaic virus (TMV) nano wire of dopamine, and its diameter is 18 ~ 40nm, and length is 300nm ~ 20 μm, and the thickness of poly-dopamine clad is 1 ~ 10nm.
7.
according to claimpreparation method described in 1, is characterized in that: described to utilize poly-dopamine coated in gained nanowire surface to carry out functional modification step as follows:
A. tobacco mosaic virus (TMV) nano wire Surface coating being gathered dopamine evenly spreads in alkaline buffer solution, forming reactions solution, and stirs;
B. in reaction solution described in step a, add the solution containing gold ion, or add, containing amino or sulfydryl, there is bioactive molecule; After reacting completely, through dialysis, lyophilization, obtain surface-functionalized tobacco mosaic virus (TMV) nanowire composite.
8.
according to claimpreparation method described in 7, is characterized in that: in step a, and the mass concentration of described reaction solution is 0.1 ~ 2.0mg/mL, and described mixing time is 0.5 ~ 2 hour; In step b, described in react completely refer under 4 DEG C of conditions react 2 ~ 24 hours, it is that 10 ~ 1,000,000 daltonian bag filters are dialysed 24 ~ 48 hours in pure water that described dialysis refers to molecular cut off.
9.
according to claimpreparation method described in 7, is characterized in that: in step a, and described alkaline buffer solution is Tris buffer solution, the one in phosphate buffered solution or sodium carbonate-bicarbonate buffer; Described alkaline buffer solution pH value is 7.8 ~ 8.5, and molar concentration is 10 ~ 100mM.
10. basis
claimpreparation method described in 7, is characterized in that: in step b, and the described solution containing gold ion is aqueous solution of chloraurate, and its mass concentration is 0.01 ~ 10mg/mL; Described is doxorubicin hydrochloride or ring-type arginine-glycine-aspartic acid polypeptide containing the bioactive molecule that has that is amino or sulfydryl; Described is 1 ~ 20mg/mL containing the bioactive molecular mass concentration that has that is amino or sulfydryl.
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