CN109568250A - Self-healing hydrogel and its preparation method and application - Google Patents
Self-healing hydrogel and its preparation method and application Download PDFInfo
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Abstract
The present invention relates to self-healing hydrogels and its preparation method and application, belong to medical material field.The present invention provides self-healing hydrogels, it is that the raw material comprising polyethyleneimine and the more aldehyde of chondroitin sulfate is prepared.The present invention also provides the preparation methods and purposes of the self-healing hydrogel.Self-healing hydrogel provided by the invention not only has destroyed after self-regeneration ability, there is good rheological property, mechanical strength, photo-thermal effect simultaneously, can effectively killing tumor cell, inhibit the postoperative recurrence of tumour, be a kind of antitumor timbering material of great potential.
Description
Technical field
The present invention relates to self-healing hydrogels and its preparation method and application, belong to medical material field.
Background technique
In the treatment of tumor patient, prevention of postoperative recurrence is most important.Conventional treatment method includes adjuvant chemotherapy at present,
Endocrine therapy and radiotherapy etc., but following some toxic reactions and systemic side effects are very important.Due to multiple types
Tumor recurrence usually since part, such as tumor of breast, thus propose that the biological support of functional molecular will be loaded in recent years
Material (such as hydrogel, biomembrane etc.) introduces tumor locus to realize killing tumor cell in situ, inhibit controlling for tumor recurrence
Treat strategy.
Hydrogel is a kind of ideal organizational project repair materials, is got the attention in therapeutic field of tumor.But its
In application, there are still some shortcomings: first is that in complicated vivo environment, influence of the hydrogel vulnerable to outside stimulus, thus
Effect cannot be played consistently；Second is that the structural intergrity of hydrogel is easily destroyed, local fracture occurs, and then treatment is caused to be imitated
Fruit is affected, and can also interfere with the reparation of organization space and the Growth and Differentiation of cell.And self-healing hydrogel has self-regeneration
Ability.When being exposed to monkey wrench, there is the ability restored to original state.After being damaged, self-healing water-setting
Glue can realize healing rapidly by cross-linked structure or chemical bond.
Therefore, exploitation has the hydrogel of good self-healing performance, and is applied to the prevention and treatment of tumour, has important meaning
Justice.
Summary of the invention
The present invention is directed at least solve one of the technical problems existing in the prior art.For this purpose, one object of the present invention
It is to provide self-healing hydrogel, the object of the invention is also to provide the preparation method of the self-healing hydrogel and purposes.
The present invention provides self-healing hydrogels, it is the raw material preparation comprising polyethyleneimine and the more aldehyde of chondroitin sulfate
It forms.
Further, the weight proportion of the raw material are as follows: 90 parts of the more aldehyde of 15~90 parts of polyethyleneimine, chondroitin sulfate.
Further, the self-healing hydrogel meets at least one of following:
The polyethyleneimine is branching type polyethyleneimine；
The molecular weight of the polyethyleneimine is 1.8kDa；
The more aldehyde of chondroitin sulfate are prepared by the following method to obtain: chondroitin sulfate being dissolved in water, high iodine is added
Sour sodium, chondroitin sulfate: sodium metaperiodate mass ratio be 5:1.35, under the conditions of being protected from light in 20 DEG C react 6 hours to get.
Further, raw material also includes modified graphene, and the modified graphene is by polyethyleneimine and graphene oxide
It is obtained by amidation process.
Further, the self-healing hydrogel meets at least one of following:
The partial size of the modified graphene is 100nm；
The modified graphene with a thickness of 3~4nm；
The modified graphene is prepared by the following method to obtain: taking graphene oxide, 1- (3- dimethylamino-propyl) -3- second
Base carbodiimide hydrochloride, n-hydroxysuccinimide and polyethyleneimine, in reaction dissolvent sufficiently react to get；
Preferably, the modified graphene is prepared by the following method to obtain: it is molten that graphene oxide is dispersed in reaction
In agent, 1- (3- dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride and n-hydroxysuccinimide is added, is uniformly mixed,
Then polyethyleneimine is added, sufficiently reaction to get；
The reaction dissolvent is phosphate buffer；
The pH=7.4 of the phosphate buffer；
Graphene oxide: 1- (3- dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride: n-hydroxysuccinimide:
The mass ratio of polyethyleneimine is 20:85.8:102:200；
After polyethyleneimine is added, mixture is ultrasonically treated 2 hours in 0~4 DEG C, then sufficiently reaction at room temperature；
The graphene oxide is prepared by the following method to obtain: by graphite: KMnO4Mass ratio is added to dense for 0.3:1.8
H2SO4: dense H3PO4Volume ratio be 9:1 mixed liquor in, solid-liquid ratio 2.1:40, g/mL, in 50 DEG C react 12 hours to get；
The carboxyl-content of the graphene oxide is 0.745mmol/g；
The polyethyleneimine is branching type polyethyleneimine；
The molecular weight of the polyethyleneimine is 1.8kDa.
Further, raw material also includes 0.1~0.3 part of modified graphene.
Further, the weight proportion of the raw material are as follows: 90 parts of the more aldehyde of 30~45 parts of polyethyleneimine, chondroitin sulfate,
0.3 part of modified graphene.
Preferably, the weight proportion of the raw material are as follows: 90 parts of the more aldehyde of 30 parts of polyethyleneimine, chondroitin sulfate, modified stone
0.1 part of black alkene, alternatively, 90 parts, 0.3 part of modified graphene of the more aldehyde of 30 parts of polyethyleneimine, chondroitin sulfate.
Further, the self-healing hydrogel is prepared by the following method to obtain: taking each raw material, is respectively scattered in solvent
In, then by the solution of each raw material mix to get.
Preferably, first polyethylenimine solution and modified graphene solution are uniformly mixed, then with the more aldehyde of chondroitin sulfate
Solution mixing.Since the more aldehyde of chondroitin sulfate can be reacted with PEI and PEI-GO simultaneously, first by PEI and PEI-GO this two
A ingredient for carrying amino after mixing, then with CSMA reacts, and can guarantee the homogeneous distribution of hydrogel component, obtain nanometer
The equally distributed hydrogel of grain.
Preferably, the solvent is water.
Further, the self-healing hydrogel is prepared by the following method to obtain: the more aldehyde of chondroitin sulfate being dissolved in molten
In agent, the more aldehyde solution of chondroitin sulfate of 30wt% concentration are obtained；Prepare the branching type polyethyleneimine of 10~60wt% concentration
Solution adjusts pH to 7.4；In a solvent by modified graphene dispersion, the solution of 0.2~0.6wt% concentration is obtained；It is molten by three kinds
Liquid mixing to get.
The present invention provides the preparation methods of the self-healing hydrogel: taking each raw material, is respectively scattered in solvent, then
By the solution of each raw material mix to get.
The present invention provides the self-healing hydrogels in preparation treatment and/or the timbering material or drug of pre- anti-cancer
In purposes.
Preferably, the timbering material or drug have the function of reducing cancer return rate.
Preferably, the cancer is breast cancer.
Preferably, the timbering material or drug are for photo-thermal treatment and/or chemotherapy.
The present invention provides treatment and/or pre- anti-cancer composition, it be carried by the self-healing hydrogel it is anti-
Cancer drug is prepared.
Preferably, the anticancer drug is chemotherapeutics.
Preferably, the chemotherapeutics is Doxorubicin.
Preferably, the composition is photo-thermal treatment and/or chemotherapy timbering material or preparation.
Preferably, the composition has the function of reducing cancer return rate.
Preferably, the cancer is breast cancer.
The present invention provides self-healing hydrogels, not only have the ability of self-regeneration after being destroyed, while having good
Good rheological property, mechanical strength, photo-thermal effect, can effectively killing tumor cell, inhibit the postoperative recurrence of tumour, be one
The antitumor timbering material of kind great potential.
Detailed description of the invention
Fig. 1 is the Rheological Characterization result figure of self-healing hydrogel in test example 1；
Fig. 2 is the self-healing performance map of self-healing hydrogel in test example 2；
Fig. 3 is the photo-thermal effect figure of test example 3；
Fig. 4 is human breast cancer cell killing-efficiency result figure in test example 4；
Fig. 5 is internal mouse breast cancer recurrence rate result figure in test example 5.
Specific embodiment
The present invention provides self-healing hydrogels, it is the raw material preparation comprising polyethyleneimine and the more aldehyde of chondroitin sulfate
It forms.
The present invention is the following discovery based on inventor and completes:
The present invention is main to prepare self-healing hydrogel comprising the raw material of polyethyleneimine and the more aldehyde of chondroitin sulfate (CSMA)
If schiff base reaction occurs using the interaction between amino and aldehyde radical, generate imine linkage (- C=N-), realizes polyethylene
Combination between imines and CSMA, to form hydrogel.Schiff bases optimum reaction conditions are neutrality, hereby it is ensured that the hydrogel
Self-healing can occur in vivo.Thus the hydrogel of viscoplasticity and self-healing better performances is obtained.
The present invention can also have following additional technical feature:
According to some embodiments of the present invention, the weight proportion of the raw material are as follows: 15~90 parts of polyethyleneimine, sulfuric acid are soft
90 parts of the more aldehyde of ossein, thus obtain the preferable hydrogel of gel-forming property.
According to some embodiments of the present invention, the polyethyleneimine uses branching type polyethyleneimine.Compared to straight chain type,
The amino amount that branching type polyethyleneimine has is more, it is easier to which in conjunction with CSMA, toxicity is lower.
According to some embodiments of the present invention, the raw material for preparing of self-healing hydrogel also includes modified graphene, described to change
Property graphene is obtained by polyethyleneimine and graphene oxide by amidation process.Graphene oxide (GO) is a kind of carbon nanometer
Particle, it has good colloidal stability, surface modificability and biocompatibility, is the reason for improving hydrogel mechanical strength
Think material.In addition, the photo-thermal effect of graphene oxide and good medicament slow release performance, can also further enhance hydrogel
Oncotherapy effect.Based on the above-mentioned advantage that graphene oxide has, inventor attempts graphene oxide being introduced into self-healing
In hydrogel, to improve the mechanical property of hydrogel.Specifically, the present invention creatively uses polyethyleneimine (PEI) to repair
GO is adornd, smaller nano particle (PEI-GO) is formd, the dispersibility in physiological environment and is had good stability in vivo.PEI-GO
Due to engaging amino on surface, it can help GO that the reversible covalent reaction based on schiff bases occurs, be able to further promote water
The formation of gel, the mechanical property for improving hydrogel, thus obtain having good rheological performance, self-healing performance, mechanical strength
With the hydrogel of biocompatibility.Simultaneously as the photo-thermal effect and drug delivery function of PEI-GO, subject hydrogel is matched
Light combination heat cure, anticancer drug are used in conjunction with, can effectively killing tumor cell, inhibit tumour postoperative recurrence.
According to some embodiments of the present invention, self-healing hydrogel is prepared by the following method to obtain: chondroitin sulfate is more
Aldehyde is dissolved in solvent, obtains the more aldehyde solution of chondroitin sulfate of 30wt% concentration；The branching type for preparing 10~60wt% concentration is poly-
Aziridine solution adjusts pH to 7.4；In a solvent by modified graphene dispersion, the solution of 0.2~0.6wt% concentration is obtained；
By three kinds of solution mix to get.Inventor is by investigating material concentration discovery, the plastic in above-mentioned concentration range, plastic efficiency
It is higher.
The solution of the present invention is explained below in conjunction with embodiment.It will be understood to those of skill in the art that following
Embodiment is merely to illustrate the present invention, and should not be taken as limiting the scope of the invention.Particular technique or item are not specified in embodiment
Part, it described technology or conditions or is carried out according to the literature in the art according to product description.Agents useful for same or instrument
Production firm person is not specified in device, and being can be with conventional products that are commercially available.
The preparation of the more aldehyde of 1 chondroitin sulfate of embodiment (CSMA)
5g chondroitin sulfate (the finished product sulfuric acid Chondroitin A sodium salt of purchase) is dissolved in 100mL deionized water, is added
1.35g sodium metaperiodate.Mixed solution is placed in dark surrounds, is stirred and evenly mixed at 20 °C 6 hours.Then gained is molten
Liquid was with deionized water dialysis 3 days.The more aldehyde of chondroitin sulfate (CSMA) are obtained after final freeze-drying.It is soft using following methods measurement sulfuric acid
The degree of oxidation of ossein: negating liquid 5mL after answering, and 10mL sodium bicarbonate is added and neutralizes, and adds 20% liquor kalii iodide 2mL analysis
Unreacted iodine out, is titrated with hypo solution, and starch is indicator.
The preparation of 2 graphene oxide of embodiment (GO)
By the dense H of 40mL2SO4: dense H3PO4(volume ratio 9:1) mixed liquor is added in 250mL flask, is then added
0.3g powdered graphite and 1.8g KMnO4Mixture.Obtained mixed solution is stirred 12 hours at 50 DEG C.Later, it will mix
It closes object and is poured into the H that 0.3mL is added dropwise on ice2O2And be stirred continuously, it reacts 30 minutes.By mixture with the speed of 8000rpm
Degree is centrifuged 30 minutes and removes supernatant liquor.By sediment deionized water, 0.2M HCl and ethyl alcohol are successively washed, are repeated 3 times,
It is washed again with anhydrous ether.Product is dried in vacuo at 37 DEG C, obtains graphene oxide (GO).It is measured by acid-base titration
The carboxyl amount of GO: GO is dissolved in deionized water, in acidity, NaOH is added dropwise and is neutralized to pH=7, calculates NaOH consumption, by
This carboxyl-content for calculating GO is 0.745mmol/g.
The preparation of 3 modified graphene BPEI-GO of embodiment
GO is prepared according to the method for embodiment 2, the 20mg GO being lyophilized is dispersed in PBS buffer solution (i.e. phosphate-buffered
Liquid, pH=7.4) in, ultrasound 1 hour.Then by the 1- of 85.8mg (3- dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride
(EDC) it is added in GO dispersion liquid with the n-hydroxysuccinimide of 102mg (NHS).Ultrasonic treatment is after 15 minutes, by 200mg
The aqueous solution of branching type polyethyleneimine (BPEI, molecular weight 1.8kDa) is added in GO dispersion liquid.Then by mixture in 0
~4 DEG C are ultrasonically treated 2 hours, and are stirred at room temperature overnight.By gained BPEI-GO dispersion by centrifugal ultrafiltration (10kDa,
3,000rpm) washing obtains BPEI-GO for several times to remove unreacted BPEI.After measured, the partial size of gained BPEI-GO is
100nm, with a thickness of 3~4nm.
The preparation of the CSMA/BPEI self-healing hydrogel of the present invention of embodiment 4
A certain amount of CSMA (being prepared according to embodiment 1) is dissolved in deionized water, the CSMA for obtaining 30wt% concentration is molten
Liquid.Branching type polyethyleneimine (BPEI, molecular weight 1.8kDa) is diluted with deionized water, obtains 10,20,30,40 and respectively
The solution of 60wt% final concentration adjusts pH to 7.4.Two kinds of ingredients are mixed into (300 μ LCSMA, 150 μ LBPEI), it can shape immediately
At self-healing hydrogel of the present invention.
The preparation of the CSMA/BPEI/BPEI-GO self-healing hydrogel of the present invention of embodiment 5
A certain amount of CSMA (being prepared according to embodiment 1) is dissolved in deionized water, the CSMA for obtaining 30wt% concentration is molten
Liquid.Branching type polyethyleneimine (BPEI, molecular weight 1.8kDa) is diluted with deionized water, obtains 10,20,30,40 and respectively
The solution of 60wt% final concentration adjusts pH to 7.4.BPEI-GO (is prepared into) dispersion in deionized water according to embodiment 3, is obtained
To the solution of 0.2,0.4 and 0.6wt% final concentration.First polyethylenimine solution and modified graphene solution are uniformly mixed, then
(300 μ LCSMA, 150 μ LBPEI, 50 μ LBPEI-GO) is mixed with the more aldehyde solution of chondroitin sulfate, can form the present invention immediately
Self-healing hydrogel.
The raw material proportioning of 1 self-healing hydrogel of table
Embodiment 6 carries the preparation of the CSMA/BPEI/BPEI-GO self-healing hydrogel of Doxorubicin (DOX)
1mg DOX is dissolved in 1mL deionized water, 6mg/mL BPEI-GO 1mL is added and carries out load medicine, is stirred overnight.
Three times with ultra-filtration centrifuge tube (10kDa, 3000rpm) centrifugation, washing, the BPEI-GO-DOX of load medicine is obtained after removing free DOX.
Ultraviolet specrophotometer measures free DOX solution absorbance, and DOX standard curve is Y=0.01266X-0.02562；X:DOX is dense
Degree, mg/mL；Y: absorbance.It is 597.48 μ g, encapsulation rate 59.75%, by 50 μ L that 1mL BPEI-GO drugloading rate, which is calculated,
After BPEI-GO-DOX is mixed with 150 μ LBPEI, then the hydrogel for carrying DOX is mixed to get with 300 μ L CSMA.
Beneficial effects of the present invention are proved below by way of test example.
Experimental animal: Balb/c female mice, 4-6 week old are provided by Fukang Biotechnology Co., Ltd, China, BeiJing, China.
Experiment reagent: Doxorubicin (DOX) is obtained from Zhejiang Hai Zheng drugmaker.
The self-healing hydrogel used is tested to be prepared according to the method that foregoing embodiments are recorded.
The Rheological Characterization of the self-healing hydrogel of the present invention of test example 1
The purpose of this test is the characterization of rheology to be carried out to hydrogel, and then judge the viscoplasticity of gel.Record energy storage
Modulus (G') and loss modulus (G "), to correspond to dynamic frequency scanning and dynamic strain sweep test.Continuous strain sweep test
For characterizing the self-healing behavior of hydrogel.Detailed process are as follows: 1) apply by a small margin shear strain (1% strain, frequency=
1.0Hz) and hydrogel is made to keep gel state (G' > G ")；2) apply significantly shear strain (400% strain, frequency=
1.0Hz, 30s), lead to gel breaks (G " < G')；3) (1% strain, frequency=1.0Hz, 200s) is returned to original state.Weight
The process is recycled again several times.Strain sweep test result is shown in Fig. 1, respectively illustrate be added 300 μ L 300mg/mL CSMA and
The strain sweep of the CSMA/BPEI hydrogel of 150 μ L various concentration BPEI (100,200,300,400 and 600mg/mL) preparation is surveyed
Test result and CSMA/BPEI/BPEI-GO hydrogel strain sweep test result (300mg/mL CSMA300 μ L,
300mg/mL BPEI150 μ L and 2,4,6mg/mL BPEI-GO50 μ L).
In dynamic frequency scanning test, the storage modulus of CSMA/BPEI hydrogel is in 10-60wt%BPEI and 20-
In the concentration range of 30wt%CSMA, the concentration dependent that maximum G' value is about 1700Pa is shown.By BPEI-GO (0.2-
0.6wt%) introducing reaction system can significantly improve storage modulus, and the maximum G' value reached is about 7000Pa.
The self-healing performance of the self-healing hydrogel of the present invention of test example 2
Several blocks of CSMA/BPEI hydrogels (raw material weight proportioning of soup processed: 30 parts of BPEI, 90 parts of CSMA) side-by-side contact is placed, ten
The reparation situation of hydrogel is observed after minute.By several blocks of CSMA/BPEI/BPEI-GO hydrogels (raw material weight proportioning of soup processed: 30 parts
BPEI, 90 parts of CSMA, 0.1 part of BPEI-GO) side-by-side contact placement, the reparation situation of hydrogel is observed ten minutes later.As a result see figure
2, wherein Fig. 2A shows the self-healing of CSMA/BPEI hydrogel, is separately added into rhodamine B and trypan blue to distinguish different masses
Hydrogel；Fig. 2 B shows the self-healing of CSMA/BPEI/BPEI-GO hydrogel.A Li Xinlan and alizarin red are separately added into distinguish
The hydrogel of different masses.
It as a result, can as it can be seen that the CSMA/BPEI hydrogel of several pieces of dispersions is placed side by side to be incorporated into an entirety after ten minutes
Lifted with tweezers and bear its own weight, but after hydrogel is picked up by tweezers, because too soft can be destroyed when stretching by tweezers,
It is unable to complete tension test.CSMA/BPEI/BPEI-GO can equally be lifted with tweezers, and can be stretched, and illustrate BPEI-
The introducing of GO is so that the mechanical strength of hydrogel is obviously improved.
The photo-thermal effect of the self-healing hydrogel of the present invention of test example 3
The BPEI-GO solution of various concentration (0.2,0.4,0.6wt%), CSMA/BPEI/BPEI-GO hydrogel (30wt%
CSMA300 μ L, 15wt%BPEI150 μ L, 0.6wt%BPEI-GO50 μ L) and CSMA/BPEI hydrogel (30wt%CSMA 300
150 μ L of μ L, 15wt%BPEI) use the NIR laser of 808nm wavelength in 2.5Wcm-2Energy density under irradiate 6 minutes, simultaneously
The process is recorded with infrared thermal imager.As a result see Fig. 3, wherein Fig. 3 A is shown with NIR laser irradiation CSMA/BPEI hydrogel
With the temperature change of CSMA/BPEI/BPEI-GO hydrogel；Fig. 3 B shows molten with the BPEI-GO of NIR laser irradiation various concentration
The temperature change of liquid；It is 808nm that Fig. 3 C, which shows that CSMA/BPEI/BPEI-GO hydrogel (6mg/mL BPEI-GO) passes through wavelength,
Energy density is 2.5Wcm-2NIR laser irradiation 0,2,4 and 6 minute after near infrared imaging situation.
It can be seen from figure 3 that temperature rises to 55.5 DEG C respectively with the increase (2,4,6mg/mL) of BPEI-GO solution concentration,
59.5 DEG C and 65.4 DEG C.It also observed similar result in CSMA/BPEI/BPEI-GO hydrogel.And CSMA/BPEI water
Gel has no significant change.The experimental results showed that, the present invention is by introducing graphene oxide, gained self-healing hydrogel tool above
There is good photo-thermal effect.
The external human breast cancer cell Inhibition test of test example 4
MCF-7 cell (human breast cancer cell line) is seeded in culture dish.After being incubated for 24 hours, respectively and not by cell
Subject hydrogel (raw material weight proportioning of soup processed: 90 parts of CSMA, 30 parts of BPEI, 0.3 part of BPEI-GO) containing DOX, free DOX, not
Through NIR laser (2.5Wcm-2, 5 minutes/day) irradiation but carry DOX hydrogel (hydrogel-DOX, according to embodiment 6 make
It is standby), and subject hydrogel without DOX but through NIR laser irradiation (raw material weight proportioning of soup processed: 90 parts of CSMA, 30 parts of BPEI, 0.3 part
BPEI-GO), carry DOX and subject hydrogel (hydrogel-DOX, according to embodiment 6 prepare) through NIR laser irradiation into
Row co-cultures, and each group dosage is 50 μ L.With mtt assay test hydrogel to the killing-efficiency of tumour cell.As a result see Fig. 4.
As a result as it can be seen that being respectively provided with 44.58%, 5.20% at the 1st, 2 and 3 day with the free DOX MCF-7 cell co-cultured
With 2.92% cell survival rate.Due to the sustained release of drug in hydrogel, the hydrogel for carrying DOX shows decline
But the cytotoxicity that the time is more permanent.Hydrogel without containing DOX passes through NIR laser irradiation (2.5Wcm-2, 5 minutes/processing/
It) after, the 1st, 2 and 3 day cell survival rate is respectively 58.71%, 43.67% and 36.60%, and which show photo-thermal therapies
Lethal effect.And the killing-efficiency of tumour cell can be improved in chemistry-photo-thermal therapy synergistic effect, at the 1st, 2 and 3 day
Cell survival rate is respectively 37.8%, 22.8% and 9.2%.
It is above-mentioned the experimental results showed that, CSMA/BPEI/BPEI-GO hydrogel of the present invention have ideal cancer cell killing make
With.
Mammary gland of mouse cancer recurrence is tested in 5 body of test example
Mouse is randomly divided into 6 groups.After mouse long to 8 weeks, 1.0 × 10 are injected in right chest mammary fat pad64T1
Cell.When tumour is long to 200mm3It is drawn off when size, but retains one layer of surrounding skin to observe tumor post-operation recurrence feelings
Condition.A is injected respectively to 6 groups of mouse) physiological saline (200 μ L), B) free DOX (5mg/kg, 200 μ L), C&D) without DOX
CSMA/BPEI/BPEI-GO hydrogel (80mm3), E&F) carry the CSMA/BPEI/BPEI-GO hydrogel (5mg/kg) of DOX.
Wherein, the raw material weight proportioning of soup processed of the CSMA/BPEI/BPEI-GO hydrogel is equal are as follows: 90 parts of CSMA, 30 parts of BPEI, 0.3 part
BPEI-GO.NIR laser irradiation (2.5W cm of D group and progress in F group 24 hours after surgery-2, 5 minutes).Monitoring one in every two days
The recurrence of secondary weight and tumour.As a result see Fig. 5.
As a result as it can be seen that the D group hydrogel without DOX fails to inhibit the recurrence of cancer after laser irradiation.Receive free
DOX treatment B group and carry E group of the DOX without laser irradiation, final cancer return rate is 66.7%.But carry DOX
The time of the B group cancer return of E group without the laser irradiation DOX treatment more free than receiving is about 7 days late, shows for DOX to be loaded into
The sustained release that drug may be implemented in hydrogel extends the action time of drug cytotoxicity.It is controlled in joint chemistry-photo-thermal
In the F group for the treatment of, final cancer return rate is 33.3%, shows the present invention with photo-thermal therapy, anti-cancer agent in combination in use, can
To effectively inhibit tumor post-operation recurrence.
It should be noted that particular features, structures, materials, or characteristics described in this specification can any one or
It can be combined in any suitable manner in multiple embodiments.In addition, without conflicting with each other, those skilled in the art can incite somebody to action
The feature of difference embodiment described in this specification and different embodiments is combined.
Claims (12)
1. self-healing hydrogel, it is characterized in that: it is that the raw material comprising polyethyleneimine and the more aldehyde of chondroitin sulfate is prepared.
2. self-healing hydrogel as described in claim 1, it is characterized in that: the weight proportion of the raw material are as follows: polyethyleneimine
15~90 parts, 90 parts of the more aldehyde of chondroitin sulfate.
3. self-healing hydrogel as claimed in claim 1 or 2, it is characterized in that: meeting at least one of following:
The polyethyleneimine is branching type polyethyleneimine；
The molecular weight of the polyethyleneimine is 1.8kDa；
The more aldehyde of chondroitin sulfate are prepared by the following method to obtain: chondroitin sulfate are dissolved in water, sodium metaperiodate is added,
Chondroitin sulfate: sodium metaperiodate mass ratio be 5:1.35, under the conditions of being protected from light in 20 DEG C react 6 hours to get.
4. the self-healing hydrogel as described in claims 1 to 3 any one, it is characterized in that: raw material also includes modified graphene,
The modified graphene is obtained by polyethyleneimine and graphene oxide by amidation process.
5. self-healing hydrogel as claimed in claim 4, it is characterized in that: meeting at least one of following:
The partial size of the modified graphene is 100nm；
The modified graphene with a thickness of 3~4nm；
The modified graphene is prepared by the following method to obtain: taking graphene oxide, 1- (3- dimethylamino-propyl) -3- ethyl carbon
Diimmonium salt hydrochlorate, n-hydroxysuccinimide and polyethyleneimine, in reaction dissolvent sufficiently react to get；
Preferably, the modified graphene is prepared by the following method to obtain: graphene oxide is dispersed in reaction dissolvent,
1- (3- dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride and n-hydroxysuccinimide is added, is uniformly mixed, then plus
Enter polyethyleneimine, sufficiently reaction to get；
The reaction dissolvent is phosphate buffer；
The pH=7.4 of the phosphate buffer；
Graphene oxide: 1- (3- dimethylamino-propyl) -3- ethyl-carbodiimide hydrochloride: n-hydroxysuccinimide: poly- second
The mass ratio of alkene imines is 20:85.8:102:200；
After polyethyleneimine is added, mixture is ultrasonically treated 2 hours in 0~4 DEG C, then sufficiently reaction at room temperature；
The graphene oxide is prepared by the following method to obtain: by graphite: KMnO4Mass ratio is that 0.3:1.8 is added to dense H2SO4:
Dense H3PO4Volume ratio be 9:1 mixed liquor in, solid-liquid ratio 2.1:40, g/mL, in 50 DEG C react 12 hours to get；
The carboxyl-content of the graphene oxide is 0.745mmol/g；
The polyethyleneimine is branching type polyethyleneimine；
The molecular weight of the polyethyleneimine is 1.8kDa.
6. self-healing hydrogel as described in claim 4 or 5, it is characterized in that: raw material also includes modified graphene 0.1~0.3
Part.
7. the self-healing hydrogel as described in claim 1~6 any one, it is characterized in that: the weight proportion of the raw material are as follows:
90 parts, 0.3 part of modified graphene of the more aldehyde of 30~45 parts of polyethyleneimine, chondroitin sulfate；Preferably, the weight of the raw material is matched
Than are as follows: 90 parts of the more aldehyde of 30 parts of polyethyleneimine, chondroitin sulfate, 0.1 part of modified graphene, alternatively, 30 parts of polyethyleneimine, sulphur
More 90 parts of the aldehyde of aching and limp ossein, 0.3 part of modified graphene.
8. the self-healing hydrogel as described in claim 1~7 any one, it is characterized in that: being prepared by the following method to obtain: taking
Each raw material, is respectively scattered in solvent, then by the solution of each raw material mix to get；Preferably, first by polyethylenimine solution
It is uniformly mixed with modified graphene solution, then mixed with the more aldehyde solution of chondroitin sulfate；Preferably, the solvent is water.
9. self-healing hydrogel as claimed in claim 8, it is characterized in that: being prepared by the following method to obtain: by chondroitin sulfate
More aldehyde are dissolved in solvent, obtain the more aldehyde solution of chondroitin sulfate of 30wt% concentration；Prepare the branching type of 10~60wt% concentration
Polyethylenimine solution adjusts pH to 7.4；In a solvent by modified graphene dispersion, the molten of 0.2~0.6wt% concentration is obtained
Liquid；By three kinds of solution mix to get.
10. the preparation method of self-healing hydrogel described in claim 1~9 any one, it is characterized in that: taking each raw material, respectively
Be scattered in solvent, then by the solution of each raw material mix to get.
11. self-healing hydrogel described in any one of claim 1 to 9 is in preparation treatment and/or the bracket material of pre- anti-cancer
Purposes in material or drug；Preferably, the timbering material or drug have the function of reducing cancer return rate；Preferably, institute
Stating cancer is breast cancer；Preferably, the timbering material or drug are for photo-thermal treatment and/or chemotherapy.
12. treatment and/or pre- anti-cancer composition, it is characterized in that: it be by it is described in any one of claim 1 to 9 from
Healing hydrogel carries anticancer drug and is prepared；Preferably, the anticancer drug is chemotherapeutics；Preferably, the chemotherapy
Drug is Doxorubicin；Preferably, the composition is photo-thermal treatment and/or chemotherapy timbering material or preparation；Preferably, described group
Closing object has the function of reducing cancer return rate；Preferably, the cancer is breast cancer.
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| CN102573944A (en) * | 2009-07-02 | 2012-07-11 | 亚洲大学校产学协力团 | In situ forming hydrogel and biomedical use thereof |
| CN108744033A (en) * | 2018-05-31 | 2018-11-06 | 西南交通大学 | The preparation method and products thereof of the self-healing hydrogel of injectable |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102573944A (en) * | 2009-07-02 | 2012-07-11 | 亚洲大学校产学协力团 | In situ forming hydrogel and biomedical use thereof |
| CN108744033A (en) * | 2018-05-31 | 2018-11-06 | 西南交通大学 | The preparation method and products thereof of the self-healing hydrogel of injectable |
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