CN105778139B - The construction method of functional form imitating cell outer-layer film stereochemical structure coating - Google Patents

The construction method of functional form imitating cell outer-layer film stereochemical structure coating Download PDF

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CN105778139B
CN105778139B CN201610120275.8A CN201610120275A CN105778139B CN 105778139 B CN105778139 B CN 105778139B CN 201610120275 A CN201610120275 A CN 201610120275A CN 105778139 B CN105778139 B CN 105778139B
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coating
cell outer
layer film
stereochemical structure
imitating cell
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CN105778139A (en
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宫永宽
邢成美
鲍丽丽
姜海涛
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Northwest University
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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
    • C08J7/04—Coating
    • C08J7/06—Coating with compositions not containing macromolecular substances
    • C08J7/065—Low-molecular-weight organic substances, e.g. absorption of additives in the surface of the article
    • C—CHEMISTRY; METALLURGY
    • C03—GLASS; MINERAL OR SLAG WOOL
    • C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C17/00—Surface treatment of glass, not in the form of fibres or filaments, by coating
    • C03C17/001—General methods for coating; Devices therefor
    • C03C17/002—General methods for coating; Devices therefor for flat glass, e.g. float glass
    • C—CHEMISTRY; METALLURGY
    • C03—GLASS; MINERAL OR SLAG WOOL
    • C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C17/00—Surface treatment of glass, not in the form of fibres or filaments, by coating
    • C03C17/28—Surface treatment of glass, not in the form of fibres or filaments, by coating with organic material
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J3/00—Processes of treating or compounding macromolecular substances
    • C08J3/12—Powdering or granulating
    • C08J3/126—Polymer particles coated by polymer, e.g. core shell structures
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2323/00—Characterised by the use of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Derivatives of such polymers
    • C08J2323/02—Characterised by the use of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Derivatives of such polymers not modified by chemical after treatment
    • C08J2323/10—Homopolymers or copolymers of propene
    • C08J2323/12—Polypropene
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2367/00—Characterised by the use of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Derivatives of such polymers
    • C08J2367/04—Polyesters derived from hydroxy carboxylic acids, e.g. lactones
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2479/00—Characterised by the use of macromolecular compounds obtained by reactions forming in the main chain of the macromolecule a linkage containing nitrogen with or without oxygen, or carbon only, not provided for in groups C08J2461/00 - C08J2477/00

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Abstract

The invention discloses a kind of methods in substantially any material surface building imitating cell outer-layer film stereochemical structure coating, material is dipped in aqueous dopamine solution coats poly-dopamine first by it, then by dicarboxyl polyethylene glycol HOOC-PEG-COOH or carboxy polyethylene glycol PEG-COOH, imitating cell outer-layer membrane structure copolymer p MEN containing active ester group and Phosphorylcholine group pendant is successively reacted with the amino of poly-dopamine coating surface in aqueous solution to be fixed on the surface of the material, form imitating cell outer-layer film stereochemical structure stable against biological contamination coating, finally with the targeted molecular containing amino and coating surface polyethylene glycol terminal carboxyl group covalent bond, obtain imitating cell outer-layer film stereochemical structure coating.The present invention improves Biocompatibility and assigns the function of design, the coating is implemented in nanoparticle surface, " stealth " effect of Nano medication in vivo and circulation time in blood can be increased substantially, the enrichment release in lesions position is significantly increased.

Description

The construction method of functional form imitating cell outer-layer film stereochemical structure coating
Technical field
The present invention relates to the buildings of imitating cell outer-layer film stereochemical structure coating and performance to optimize, and belongs to process for modifying surface neck Domain.
Technical background
In clinical application, still different degrees of there are infection, blood coagulation and arts for existing bio-medical material and device Afterwards the problems such as hyperblastosis, the undesirable problem of these biocompatibilities, which has become, restricts bio-medical material and Nano medication In the key factor of clinical application.Currently, carrying out surface modification to material is to improve the very effective mode of its biocompatibility. But how simply and efficiently to improve modified material stability on the surface of the material and biocompatibility is current research and application It is crucial.
In general, hydrated sheath, benefit can be formed by improving material surface hydrophily by improving the biocompatibility of material Improve the biocompatibility of material in vivo with the repulsive interaction between hydrated sheath and protein molecule etc. in vivo molecule.
Phosphorylcholine is the hydrophilic functional groups that the positive and negative charge of equivalent is had in extracellular tunic, can combine a large amount of water Molecule forms one layer of hydration layer, shows good biocompatibility and anti-pollution effect.With the polymer of the group containing Phosphorylcholine Hydrophilic modifying is carried out to material surface, surface is made to be not easy the reaction such as adsorbed proteins, adhesion and aggregation blood platelet, so as to eliminating or It reduces material and is identified and occurs rejection in vivo, can effectively improve the biocompatibility of material.Gong et al. (Journal of Membrane Science, 2014,452,29) is with the copolymer (PMBT) containing Phosphorylcholine group The material surfaces such as modified polypropene doughnut, the modified adsorbance to protein and blood platelet etc. reduce by 90 or more.This is poly- Closing object has broad prospect of application to the modified medical instrument and material directly contacted with blood.
Summary of the invention
The purpose of the present invention is to propose to a kind of foundation in any material surface constructing function type imitating cell outer-layer film solid knot The universal method of structure coating, and anti-non-specific protein absorption, bacterium and other cell adherences, targeting etc. are carried out, And it establishes with related data, the method for carrying out coating performance optimization in surface plasma body resonant vibration instrument the real time measure aqueous solution.
The present invention realizes that process is as follows:
A kind of construction method of imitating cell outer-layer film stereochemical structure coating: material is dipped in aqueous dopamine solution applies first Poly-dopamine is covered, then by dicarboxyl polyethylene glycol HOOC-PEG-COOH or carboxy polyethylene glycol PEG-COOH, contains active ester The imitating cell outer-layer membrane structure copolymer p MEN of group and Phosphorylcholine group pendant is successively applied with poly-dopamine in aqueous solution The amino reaction of layer surface is fixed on the surface of the material, forms imitating cell outer-layer film stereochemical structure stable against biological contamination coating, finally uses Targeted molecular containing amino and coating surface polyethylene glycol terminal carboxyl group covalent bond, obtain imitating cell outer-layer film stereochemical structure Coating；The material is selected from glass, polycarbonate, stainless steel, polytetrafluoroethylene (PTFE), polypropylene.
Above-mentioned poly-dopamine, which mediates, applies layer building 0.2 ~ 2.0 mg/ml of concentration, the aqueous dopamine solution of pH 7.0 ~ 8.5 Dip-coating, spraying and spin-coat process are carried out to material at room temperature；After aqueous dopamine solution treated material with water cleaning successively Immerse dicarboxyl polyethylene glycol or carboxy polyethylene glycol, PMEN or the ammonia directly into PMENP aqueous solution with poly-dopamine surface Base combines building imitating cell outer-layer film stereochemical structure coating with amido bond；Polyethylene glycol terminal carboxyl group is activated through EDC and NHS solution In conjunction with amidation process occurs with amino afterwards.
Above-mentioned targeted molecular is ethylenediamine folic acid, peptide chain, protein or enzyme.
In above-mentioned imitating cell outer-layer film stereochemical structure coating the superficial density of polyethylene glycol and Phosphorylcholine group and its it Between ratio controlled with concentration and reaction time is added, the additional amount and its reaction time parameter of targeted molecular are for regulating and controlling target The power acted on to the superficial density and targeting of molecule, wherein 100 ~ 1000 ng/cm of coating surface polyethyleneglycol content2, 1000 ~ 5000 ng/cm of Phosphorylcholine group content2, 20 ~ 500 ng/cm of targeted molecular content2。
The advancing angle that the coating surface that the present invention constructs is contacted with water is 40 ~ 65 °, and receding angle is 8 ~ 30 °；It is pure to ox blood Protein adsorption quantity is reduced to 2 ~ 50 ng/cm2, 5 ~ 150ng/cm is reduced to the adsorbance of fibrinogen2, to platelet adhesion reaction Amount reduces 80 ~ 99.8%, increases by 2 ~ 20 times to the specificity interaction of design.
Advantages of the present invention: (1) applied widely.May be used with nearly the object of any material and shape, including metal and Its oxide, glass, ceramics, plastics, a variety of nano particles and the polytetrafluoroethylene (PTFE) etc. for being most difficult to adherency are that a kind of material surface changes " universal type " common technology method of property.(2) use process is easy.It can accomplish that dip-coating is completed to material in room temperature aqueous solution Surface is modified；It can also be coated by simple procedures such as spraying, spin coatings.(3) coating functionalization is convenient, flexible, performance can be excellent Change.Coating functionalization process can be carried out gradually, can also combine, be integrated in polymer chain once combine be fixed on poly- DOPA Amine surface.Regulate and control the superficial density and ratio of PEG and Phosphorylcholine group, imitating cell outer-layer film stereochemical structure coating easy to accomplish Performance optimization；Change or regulation surface functional group such as targets group, the function of coating can be changed and optimize its performance. (4) bionic coating has no toxic side effect.The material for constituting imitating cell outer-layer film stereochemical structure coating has been studied using many years, without bad Reaction report.Applying layer building is that imitative mussel adhesion process carries out in aqueous solution, non-environmental-pollution and nuisance residual.
Detailed description of the invention
Fig. 1 is the building process schematic diagram of functional form imitating cell outer-layer film stereochemical structure coating；
Fig. 2 is that the adsorbance of chip surface adsorbed molecules in different disposal process surface plasma body resonant vibration instrument changes signal Figure.
Specific embodiment
The construction method of imitating cell outer-layer film stereochemical structure coating of the present invention is as follows:
1, poly-dopamine mediates the preparation of coating: the aqueous dopamine solution (pH 7.5 ~ 8.6) of 0.1 ~ 2 mg/mL is prepared, in Modified material surface is being intended in dip-coating at room temperature, forms stable poly-dopamine coating.
2, in poly-dopamine layer surface constructing function type imitating cell outer-layer film stereochemical structure coating:
1) material for being coated with poly-dopamine is dipped in the carboxy polyethylene glycol aqueous solution through overactivation, it is anti-by amidation The flexibility that should be flexed outward in the polyethylene glycol of poly-dopamine surface bond design flow as imitating cell outer-layer film stereochemical structure is long Chain；
2) then in the imitating cell outer-layer membrane structure copolymer containing active ester group and Phosphorylcholine group pendant (PMEN) dip-coating in aqueous solution continues covalent through amidation process in the material surface for being coated with poly-dopamine and carboxy polyethylene glycol In conjunction with PMEN, formed hydrophilic containing a large amount of extracellular tunic Phosphorylcholine group hydrophilic interface and the PEG flexed outward simultaneously The stereochemical structure coating of shell composition.This hydrophilic coating with imitating cell outer-layer film stereochemical structure, can be as cell membrane It more efficiently prevents from and reacts with internal ingredient, improve the biocompatibility of material；
3) antibiosis finally is obtained with the targeted molecular containing amino and coating surface polyethylene glycol terminal carboxyl group covalent bond Multi-functional coatings both with object pollution and targeting.
3, in poly-dopamine layer surface constructing function type imitating cell outer-layer film stereochemical structure coating, it is also possible to which combination has phosphinylidyne Choline group, carboxyl PEG, the polymer for targeting group and catechol group, one step of dip-coating is completed in aqueous solution.This use The technical process of multifunctional polymer constructing function type imitating cell outer-layer film stereochemical structure coating known to composition ratio is simple, holds Easily carry out performance optimal screening.
4, the process of coating and the performance evaluation of coating are formed, can directly be surveyed in real time online with surface plasma body resonant vibration instrument It is fixed.The building process of functional form imitating cell outer-layer film stereochemical structure coating is as shown in Figure 1.Chip surface is inhaled during different disposal The adsorbance variation schematic diagram of attached molecule is as shown in Figure 2.According to coating surface to the reduction degree of nonspecific proteins adsorbance And to specific molecular in conjunction with increase degree carry out screening and optimizing coating performance.
Present invention stepwise reaction and integrated rear single step reaction mediate coating surface building to contain phosphinylidyne gallbladder in poly-dopamine The technical process of the multifunction imitated extracellular tunic stereochemical structure coating of base groups, polyglycol chain and targeting group is simple, fits It is modified for surfaces of various materials, optimal design function characteristic is assigned while improving biocompatibility.It is artificial improving The Study on biocompatibility and production field of organ and associated materials, nano-medicament carrier, separation material and other material surfaces It has broad application prospects.
More specifically, the construction method of imitating cell outer-layer film stereochemical structure coating is as follows:
1, poly-dopamine mediates the preparation of coating: the dopamine of 0.1 ~ 2 mg/mL is prepared with commercially available reagent Dopamine hydrochloride The material of quasi- modification, is immersed in solution 1 ~ 20 hour by aqueous solution (pH 7.5 ~ 8.6) at room temperature, formed certain thickness, Stable poly-dopamine coating in water；Separation is eluted after taking out with water, drying for standby.
2, the material for being coated with poly-dopamine: 1) being dipped in by EDC by the building of imitating cell outer-layer film stereochemical structure coating and In carboxy polyethylene glycol (commercially available reagent) aqueous solution of NHS solution activation, by amidation process in poly-dopamine surface bond The long flexible chain that the polyethylene glycol of design flow is flexed outward as imitating cell outer-layer film stereochemical structure.It is fixed on the poly- second two on surface Alcohol chain density is regulated and controled by solution concentration (2 ~ 20 mg/mL) and reaction time (10 ~ 60 min), can use surface plasma body resonant vibration Instrument the real time measure.2) then in the imitating cell outer-layer membrane structure copolymer containing active ester group and Phosphorylcholine group pendant (PMEN) dip-coating in aqueous solution continues covalent through amidation process in the material surface for being coated with poly-dopamine and carboxy polyethylene glycol In conjunction with PMEN, formed hydrophilic containing a large amount of extracellular tunic Phosphorylcholine group hydrophilic interface and the PEG flexed outward simultaneously The stereochemical structure coating of shell composition.PMEN is by literature method (J. Mater. Chem. B, 2015,3,2350-2361) Preparation, is configured to 2 ~ 20 mg/mL aqueous solutions and reacts 0.5 ~ 6 h with material surface.The PMEN that reaction is fixed on surface can also use table Surface plasma resonance instrument the real time measure.3) finally with targeted molecular aqueous solution (0.1 ~ 5 mg/mL) and coating containing amino Surface polyethylene glycol terminal carboxyl group covalent bond, obtains multi-functional coatings both with stable against biological contamination and targeting.Targeted molecular The same usable concentration of binding capacity and reaction time regulation, with surface plasma body resonant vibration instrument the real time measure.
3, the process of coating and the performance data of coating are formed, can directly be surveyed in real time online with surface plasma body resonant vibration instrument It is fixed.According to coating surface to the reduction degree of nonspecific proteins adsorbance and to specific molecular in conjunction with increase degree sieve Choosing optimization coating performance.
Embodiment 1: the preparation containing active aliphatic radical group and Phosphorylcholine group binary polymer PMEN.One three neck is taken to burn Bottle, three mouthfuls respectively plus dropping funel, the return pipe with drying tube, logical nitrogen device, in 100 mL dried and clean three-neck flasks 20 ml dehydrated alcohols are added, in 70 DEG C of constant temperature, keep 30 min of this temperature, weighs 0.05 g AIBN of addition and is dissolved in 6 ml THF solution.40 ml are added dropwise and contain active 1.05 g of ester monomer MEONP, the 2.98 anhydrous second of g of the MPC of group monomer containing Phosphorylcholine Alcoholic solution is added dropwise in 4 h, reacts 20 h.Retention point will be packed into after the concentration of gained PMEN binary randomcopolymer solution The bag filter that son amount is 7000, with 3.93 phosphate aqueous solution of pH dialysis, 48 h.PMEN fluffy solid is obtained after freeze-drying.1HNMR The molar content for measuring MPC, MEONP component in functionalized polymer is respectively 89% and 11%.
Embodiment 2: the preparation containing active ester functional polymer PMENP.It is anhydrous that 10 mL are added in 100 mL three-necked bottles Ethyl alcohol, leads to nitrogen, and magnetic agitation is simultaneously gradually heated to 70 DEG C.It successively weighs active 0.140 g of ester monomer NPCEMA, contain carboxylic Base chain monomer PEGA 2.726 g and 0.805 g of MPC, and 34 mL dehydrated alcohols are added and make it dissolve.Weigh 0.037 g AIBN is added in the mixed liquor of monomer.The mixed solution of monomer is added dropwise with dropping funel, about 2 h are added dropwise.It is changed to obturator System continues to 24 h of reaction.After stopping reaction, takes out part reaction solution and is fitted into the bag filter that molecular cut off is 7000, It dialyses in the acidic aqueous solution of pH 3 ~ 4.Freeze-drying.D2In O solvent1H-NMR characterizes its structure, and group, which becomes, contains active ester Unit, MPC and PEGA molar content are respectively 12%, 69% and 29% polymer P MENP.
Embodiment 3: the online building of poly-dopamine mediation coating.Prepare the dopamine Tris-HCl (pH of 2 mg/mL 8.2) solution flows through 30 min of plasma resonance instrument chip gold surface, mobile phase elution with the flow velocity injection of 20 μ L/min Balancing and measuring fixed amount of the poly-dopamine on surface after 30 min is 148 ng/cm2。
Embodiment 4: the dip-coating building of poly-dopamine coating.The aqueous dopamine solution (pH 8.5) for configuring 1 mg/mL, with 2 ×2 cm26 h of polypropylene foil room temperature dip-coating.Room temperature is dried after impregnating, eluting in distilled water.Measure static contact angle average out to It 46 °, is substantially reduced compared with 101 ° of static contact angle of blank polypropylene foil.
Embodiment 5: polylactic acid nano SiC p surface plating poly-dopamine coating.The dopamine for configuring 0.2 mg/mL is water-soluble 5 mL of liquid (pH 8.2), polylactic acid nano particle aqueous dispersion, which is added, makes 0.5 mg/mL of its concentration.Room temperature slowly shakes 24 (poly-) aqueous dopamine solution is centrifuged off after h, plain boiled water of the polylactic acid nano particle from before coating becomes sepia.It is redispersed in Zeta becomes positive value from negative value before after in 6.0 water of pH.Meanwhile before dynamic light scattering measures nano particle diameter by coating 92 nm increase to 96 nanometers.These results prove polylactic acid nano SiC p surface plating poly-dopamine coating.
Embodiment 6: glass surface sprays poly-dopamine coating.The aqueous dopamine solution (pH 7.5) of 1.5 mg/mL is configured, It is sprayed on sheet glass (1.8 × 1.8 cm2) surface, it is saved 2 days in 90% environment of room temperature humidity.It is impregnated in distilled water, ultrapure water Room temperature is dried after elution.39 ± 2 ° of static contact angle average out to are measured in water, the static contact angle average 28 with blank glass piece It compares for ± 2 ° and is changed significantly.
Embodiment 7: building carboxy polyethylene glycol coating.Prepare the PBS(pH 6.5 of 2 mg/mL carboxy polyethylene glycols) water Solution, wherein EDC the and 10mg/ml NHS comprising 10 mg/ml carrys out activated carboxyl.By the solution with 10 μ L/min flow velocity streams The poly-dopamine for crossing the building of embodiment 3 mediates 40 min of coating, measures carboxy polyethylene glycol after 30 min of mobile phase stripping equilibria Fixed amount on surface is 66 ng/cm2。
Embodiment 8: surface bond polymer with simulated cellulosa membrane structure PMEN91.Prepare 5 mg/mL PMEN91 polymer Aqueous solution (pH 6.5) flows through the carboxy polyethylene glycol coating surface of the building of embodiment 7 after completely dissolution with 5 μ L/min flow velocitys It is 380 ng/cm that fixed amount of the PMEN91 on surface is measured after 200 min, 30 min of mobile phase stripping equilibria2.What is constructed is imitative thin The adsorbance of extracellular 1.0 mg/mL BSA and Fg albumen of tunic stereochemical structure coating surface film on-line determination is respectively 0.6 ng/ cm2And 7.0 ng/cm2.Compared with unmodified gold surface, the imitating cell outer-layer film stereochemical structure coating surface is to these non-spies The absorption inhibiting rate of foreign preteins matter reaches 96% or more.
Embodiment 9: imitating cell outer-layer film stereochemical structure coating surface functionalization.The imitating cell outer-layer film that embodiment 8 constructs Stereochemical structure coating surface polyethylene glycol carboxyl is passed through 0.2 mg/mL second two after EDC and NHS activation with 5 μ L/min flow velocitys 60 min of PBS aqueous solution (pH 6.5) of amination folic acid.Tumor targeted molecular folic acid is measured after 30 min of mobile phase stripping equilibria Fixed amount on surface is 16.4 ng/cm2.The surface is up to 66 to the adsorbance of 0.5 μ g/mL folacin receptor protein alpha FR ng/cm2, targeting is obviously improved.
Embodiment 10: the online building of the imitative cell membrane stereochemical structure polymer P MENP coating containing active ester function.Match 5 mg/mL PMENP polymer P BS aqueous solutions (pH 6.5) are made, with 5 μ L/min flow velocity streams on surface plasma body resonant vibration instrument The poly-dopamine for crossing the building of embodiment 3 mediates 180 min of coating surface, measures PMENP after 30 min of mobile phase stripping equilibria and exists The fixed amount on surface is 236 ng/cm2.The adsorbance of the 1 mg/mL BSA albumen of coating surface is 3 ng/cm2。
Embodiment 11: imitating cell outer-layer film stereochemical structure applies layer building: it is water-soluble to prepare 4 mg/mL PMENP polymer P BS Liquid (pH 6.5), with 24 h of polycarbonate dip-coating for being coated with poly-dopamine coating.Drying after pure water elutes 5 times is taken out, XPS is fine Map display surface has the quaternary ammonium group signal of apparent Phosphorylcholine group, shows that PMENP polymer is integrated in aqueous solution The poly-dopamine of base mediates layer surface.
Embodiment 12: the polylactic acid nano particle surface of coating poly-dopamine coating constructs imitating cell outer-layer membrane coat.With The polylactic acid nano particle water redisperse liquid of coating poly-dopamine coating prepared by embodiment 5 and PMEN91 aqueous solution, configuration contain Nano particle 0.2 mg/mL of 1 mg/mL, PMEN91, the aqueous solution of pH 7.2,24 h of room temperature magnetic agitation.Dynamic light scattering Number average bead diameter has 96 nm before reaction to increase to 119 nanometers；There is phosphorus in the fine map upper liquid of the XPS of nano particle film surface The quaternary ammonium group and P elements signal peak of phatidylcholine group, it was demonstrated that imitate cell membrane polymer-coated in polylactic acid nano particle surface Poly-dopamine mediates on layer.

Claims (7)

1. a kind of construction method of imitating cell outer-layer film stereochemical structure coating, it is characterised in that: material is dipped in dopamine first Poly-dopamine is coated in aqueous solution, then by dicarboxyl polyethylene glycol HOOC-PEG-COOH or carboxy polyethylene glycol PEG-COOH, Imitating cell outer-layer membrane structure copolymer p MEN containing active ester group and Phosphorylcholine group pendant successively in aqueous solution with The amino reaction of poly-dopamine coating surface is fixed on the surface of the material, forms imitating cell outer-layer film stereochemical structure stable against biological contamination and applies Layer, finally with the targeted molecular containing amino and coating surface polyethylene glycol terminal carboxyl group covalent bond, obtains imitating cell outer-layer Film stereochemical structure coating.
2. the construction method of imitating cell outer-layer film stereochemical structure coating according to claim 1, it is characterised in that: poly- DOPA Amine, which mediates, applies layer building 0.2 ~ 2.0 mg/ml of concentration, and the aqueous dopamine solution of pH 7.0 ~ 8.5 at room temperature carries out material Dip-coating, spraying and spin-coat process.
3. the construction method of imitating cell outer-layer film stereochemical structure coating according to claim 2, it is characterised in that: dopamine Dicarboxyl polyethylene glycol or carboxy polyethylene glycol, PMEN are successively immersed after aqueous solution treated material with water cleaning or are directly arrived In PMENP aqueous solution with the amino on poly-dopamine surface with amido bond in conjunction with construct imitating cell outer-layer film stereochemical structure coating.
4. the construction method of imitating cell outer-layer film stereochemical structure coating according to claim 3, it is characterised in that: poly- second two In conjunction with amino amidation process occurs for alcohol terminal carboxyl group after the activation of EDC and NHS solution.
5. the construction method of imitating cell outer-layer film stereochemical structure coating according to claim 1, it is characterised in that: the target It is ethylenediamine folic acid, peptide chain, protein or enzyme to molecule.
6. according to claim 1 to 5 it is one of any described in imitating cell outer-layer film stereochemical structure coating construction method, feature Be: in imitating cell outer-layer film stereochemical structure coating the superficial density of polyethylene glycol and Phosphorylcholine group and its between ratio It is controlled with concentration and reaction time is added, the additional amount and its reaction time parameter of targeted molecular are for regulating and controlling targeted molecular Superficial density and the power of targeting effect, wherein 100 ~ 1000 ng/cm of coating surface polyethyleneglycol content2, Phosphorylcholine 1000 ~ 5000 ng/cm of group content2, 20 ~ 500 ng/cm of targeted molecular content2。
7. according to claim 1 to 5 it is one of any described in imitating cell outer-layer film stereochemical structure coating construction method, feature Be: the material is selected from glass, polycarbonate, stainless steel, polytetrafluoroethylene (PTFE), polypropylene.
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CN109575441B (en) * 2018-12-12 2021-07-30 上海金发科技发展有限公司 Polyolefin composite material with good appearance for 3D printing and preparation method thereof
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