CN110200945A - A kind of preparation method of light sensitivity DOPA amido nano-medicament carrier - Google Patents
A kind of preparation method of light sensitivity DOPA amido nano-medicament carrier Download PDFInfo
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- CN110200945A CN110200945A CN201910650691.2A CN201910650691A CN110200945A CN 110200945 A CN110200945 A CN 110200945A CN 201910650691 A CN201910650691 A CN 201910650691A CN 110200945 A CN110200945 A CN 110200945A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/69—Boron compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
A kind of preparation method of light sensitivity DOPA amido nano-medicament carrier, dopamine or derivatives thereof solution is mixed with Biological cross-linker solution, adjusting pH value is 7~8, concussion reaction is finally centrifuged, washes, the dry size range that can be obtained is 30~800nm light sensitivity DOPA amido nano-medicament carrier;The dopamine and its derivative include dopamine, levodopa;The Biological cross-linker includes Geniposide;The molar ratio of the dopamine and its derivative and Biological cross-linker is (0.5~5): 1;The resulting nano-medicament carrier of the present invention is a kind of natural photosensitizer, and size adjustable, good biocompatibility, stability are high, can load chemotherapeutics and controlled release can be improved antitumor efficiency so that two kinds of therapies of phototherapy and chemotherapy are combined.
Description
Technical field
The present invention relates to nano-medicament carrier technical fields, and in particular to a kind of light sensitivity DOPA amido nano-medicament carrier
Preparation method.
Background technique
Optical dynamic therapy (Photodynamic therapy, PDT) is a kind of effectively and without invasive oncotherapy plan
Slightly, highly toxic active oxygen species (Reactive oxide is generated using the photosensitizer of light source triggering tumor locus
Species, ROS), active oxygen species can with a variety of large biological molecules occur oxidation reaction, generate cytotoxicity cause cell by
Damage, and then killing tumor cell destroys tumor tissues.Photosensitizer is the key that photodynamic therapy, clinically traditional photosensitizer master
It to include Porphyrin-Based Sensitizer, phthalocyanines derivates, condensed ring quinones etc..However, these photoactive substances all have it is water-soluble
The defect that property is lower, photostability is poor, easily assembles.Therefore, researcher has been devoted to water solubility, high specificity, high quantum
The research of the novel photosensitive agent of yield.On the one hand, inorganic nano material such as fullerene, metal nanoparticle, graphene amount are synthesized
Son point etc. is widely used in PDT treatment as photosensitizer.On the other hand, it is developed based on biocompatible bio-molecules
Novel photosensitive agent be efficient PDT realization bring new hope.
Dopamine is a kind of neurotransmitter of catecholamines being widely present in nervous system.As a kind of small molecule
Drug has effects that treat Parkinson's disease, schizophrenia.Recent studies have found that dopamine can be pressed down by its D2R receptor
The activity of blood vessel endothelium permeability factor and vascular endothelial growth factor in tumor endothelial cell and marrow bank processed, thus
Inhibit the growth and transfer, such as gastric cancer, liver cancer, breast cancer, oophoroma etc. of cancer.In addition, in terms of nano material preparation, it is more
Bar amine generates poly-dopamine due to can occur to aoxidize auto polymerization reaction under alkaline condition and becomes a kind of and widely used receive
Rice material construction unit.Researcher has synthesized a plurality of types of functional materials using dopamine, such as nano particle, core/
Shell structure, microcapsules, film etc..These materials are widely used in biomedicine field, such as drug conveying, treatment of cancer, tissue
Engineering, antibacterial etc..
Administration nano-drug administration system provides fabulous platform for the synergistic treatment of a variety for the treatment of means.By nanometer biotechnology with
Disease treatment means combine, and are the forward positions of nanosecond science and technology and biomedicine field research.Currently, researcher has developed
A variety of nano-medicament carriers, such as nano particle, liposome, polymer micelle, vesica.In the preparation process of administration nano-drug administration system
In, several functions molecule and drug, such as targeted molecular, chemotherapeutics, photo-thermal therapy medicine are wrapped by adaptability encapsulation
Being embedded in inside nano particle can be improved drug bioavailability and reduces drug side-effect.It is encapsulated using nano material adaptability
Characteristic, be expected to building set targeting conveying, synergistic treatment in one multi-functional anti-tumor nano platform.
Summary of the invention
In order to overcome the defects of the prior art described above, the purpose of the present invention is to provide a kind of light sensitivity DOPA amido nanometers
The preparation method of pharmaceutical carrier is mainly to construct primitive with dopamine and its derivative, passes through dopamine and Biological cross-linker capital
The flat chemical bonding of Buddhist nun prepares biocompatible, water-soluble photoactive nanoparticles pharmaceutical carrier, is loaded by physico-chemical process
Chemotherapeutics, to construct the Nano medication platform of set optical dynamic therapy and chemotherapy synergistic effect;Nano medication of the present invention carries
Body is a kind of natural photosensitizer, and size adjustable, good biocompatibility, stability are high, can load chemotherapeutics and realizing controlled-release
It puts, two kinds for the treatment of means of phototherapy and chemotherapy is combined, antitumor efficiency is improved.
In order to achieve the above objectives, the technical scheme adopted by the invention is as follows:
A kind of preparation method of light sensitivity DOPA amido nano-medicament carrier, by dopamine or derivatives thereof solution and biology
Cross-linking agent solution mixing, adjusting pH value is 7~8, concussion reaction, is finally centrifuged, washes, the dry size range that can be obtained is 30
~800nm light sensitivity DOPA amido nano-medicament carrier.
Described dopamine or derivatives thereof includes dopamine, levodopa.
The Biological cross-linker includes Geniposide.
The dopamine or derivatives thereof solution concentration is 3~50mmol/L.
3~50mmol/L of the genipin solution concentration.
The volume of described dopamine or derivatives thereof and genipin solution mixed system is 0.5~50mL.
The molar ratio of described dopamine or derivatives thereof and Biological cross-linker is (0.5~5): 1.
The molar ratio of described dopamine or derivatives thereof and Biological cross-linker is specially 3~1 ﹕ 1,5 ﹕ 4 or 1 ﹕ 2.
The adjusting pH value is specifically adjusted using NaOH.
The concussion reaction, 500~1000rpm of revolving speed, preferably 500rpm;Reaction temperature be 20~70 DEG C, preferably 25~
40℃;The reaction time is 12~96h, preferably 24~36h.
The concussion reaction, revolving speed 500rpm;25~40 DEG C of reaction temperature;24~36h of reaction time.
The centrifugation, centrifugal rotational speed are 9000~12000rpm;Centrifugation time is 15min~30min.
The centrifugal rotational speed is 10000rpm.
Light sensitivity DOPA amido nano-medicament carrier of the present invention is a kind of natural photosensitizer, and tool is generated under illumination
Cytotoxic active oxygen has tumour cell lethal.
Light sensitivity DOPA amido nano-medicament carrier of the present invention has good encapsulation ability to chemotherapeutics, and
And controlled release can be carried out to drug under condition of different pH.
The invention has the benefit that
1) light sensitivity DOPA amido nano-medicament carrier of the present invention is synthesized by mild, quick method, is had good
Biocompatibility and water solubility.
2) light sensitivity DOPA amido nano-medicament carrier of the present invention can be by changing reaction density, reaction time, concussion
The reaction conditions such as speed are realized and are regulated and controled to the size of nano-medicament carrier.
3) light sensitivity DOPA amido nano-medicament carrier of the present invention has the property of natural photosensitizer, can be in tumor locus
Effectively accumulation, can be applied to the optical dynamic therapy of cancer.
4) light sensitivity DOPA amido nano-medicament carrier of the present invention can encapsulate different chemotherapeutics, and in different pH items
Controlled release is carried out under part.
Detailed description of the invention
Fig. 1 is the nano-medicament carrier SEM of the synthesis of embodiment 1, TEM image, and wherein Figure 1A is SEM image, wherein Figure 1B
It is TEM image.
Fig. 2 is that the nano-medicament carrier singlet oxygen that embodiment 1 synthesizes generates aptitude tests.
Fig. 3 is the nano-medicament carrier encapsulation chemotherapeutics that embodiment 1 synthesizes and pH response release test.
Fig. 4 is that 1 process of synthesizing nano-drugs carrier of embodiment carries out the test of MTT cell activity.
Specific embodiment
Below with reference to embodiment, the present invention will be described in detail.Unless it is defined otherwise in the description of the present invention, otherwise
Herein all technical terms be all according to persons skilled in the art it is usually used and understand conventional definitions come using.
Experimental method described in following embodiments is unless otherwise specified conventional method;The reagent and material, such as without special theory
It is bright, commercially obtain.
Embodiment 1
A kind of preparation method of light sensitivity DOPA amido nano-medicament carrier, comprising the following steps:
By the dopamine solution of 3mmol/L and the genipin solution of 3mmol/L in molar ratio 1 ﹕ 1 ratio mix, adjust
PH is 7.5, and room temperature shakes 500rpm reaction for 24 hours, is centrifuged 20min under 10000rpm, is washed with deionized water three times, vacuum drying,
Obtain nano-medicament carrier.
Fig. 1 show nano particle SEM, TEM figure obtained after dopamine and genipin cross-linked.As shown in Figure 1, this implementation
The dopamine of example preparation and the photoactive nanoparticles pharmaceutical carrier of genipin cross-linked, size uniformity is uniformly dispersed, having a size of 100~
120nm。
(1) photodynamic activity is tested
Use bis- (methylene) two malonic acid (ABDA) of 9,10- anthryl-as chemical probe pair1O2It is detected.Use laser
(1W/cm2It 635nm) is irradiated, surveys the absorbance of a solution at regular intervals.
As shown in figure 3, with the lengthening of light application time, ABDA is at 378nm after joined photoactive nanoparticles pharmaceutical carrier
Characteristic absorption peak gradually decrease, represent system and be constantly be generated1O2, this phenomenon sufficiently proves that Nano medication of the present invention carries
Body can generate the cytotoxic singlet oxygen of tool under laser irradiation.
(2) encapsulation of chemotherapeutics and pH response release test
Specific step is as follows:
The nano-carrier of 3mg/mL is mixed with 1mg/mL bortezomib (Btz) DMSO solution, concussion reaction 5h will be mixed
Liquid centrifugation, washing are three times.The nano-carrier for having loaded Btz is dispersed in the PBS buffering of different pH (pH=7.4 and pH=5.4)
In liquid, persistent oscillation at room temperature at regular intervals takes out the old PBS of 0.5mL, and with new PBS buffer solution replace from
And keeping total volume constant, UV measures the absorbance of supernatant, carries out drug by the characteristic absorption value variation of Btz at 270nm
Accumulative releasing research.
As shown in figure 3, nano-medicament carrier prepared by embodiment 1 carries out realizing controlled-release to drug under the conditions of different pH
It puts, under the physiological condition of pH=7.4, there is a small amount of Btz to discharge, under conditions of pH=5.4, chemotherapeutics Btz is substantially completely
Release.
(3) MTT cell activity is tested
By in HeLa cell inoculation to 96 porocyte culture plates, by the culture solution containing Btz, nano-carrier culture solution or
The culture solution for having loaded the nano-carrier of Btz is washed twice with HeLa cell co-culture 5h, PBS respectively, replaces fresh cultured
Base.Then laser (1W/cm is used220min 635nm) is irradiated, the cell after irradiation is cultivated for for 24 hours, dark group conduct pair
According to CCK-8 kit measurement cell survival rate.
As shown in figure 4, nano-carrier prepared by embodiment 1 is with tumour cell after co-culturing, and under dark condition, nanometer
Carrier does not act on tumour cell substantially, under illumination condition, generates and has cytotoxic singlet oxygen, can effectively inhibit swollen
Tumor cell proliferation.Nano-carrier is after having loaded chemotherapeutics Btz, and under the slightly sour environment of tumour, chemotherapeutics is discharged, right
Tumour cell produces more obvious inhibiting effect, shows nano-carrier prepared by the present invention in optical dynamic therapy and change
Treat the advantage in terms of joint antitumor application thereof.
Embodiment 2
A kind of preparation method of light sensitivity DOPA amido nano-medicament carrier, comprising the following steps:
By 9mmol/L dopamine solution and 9mmol/L genipin solution by different volumes than mixing, adjusting pH is 7.5, room
Temperature concussion 500rpm reaction for 24 hours, is centrifuged 20min under 11000rpm, is washed with deionized water three times, be dried in vacuo to get nanometer is arrived
Pharmaceutical carrier.
It is 3 ﹕ 1,2 ﹕ 1,1 ﹕ 1, the dopamine and Geniposide of preparation respectively by different volumes than mixing described in the present embodiment
The photoactive nanoparticles pharmaceutical carrier of crosslinking, size uniformity is uniformly dispersed, having a size of 200~500nm.
(1) photodynamic activity is tested
Use bis- (methylene) two malonic acid (ABDA) of 9,10- anthryl-as chemical probe pair1O2It is detected.Use laser
(1W/cm2It 635nm) is irradiated, surveys the absorbance of a solution at regular intervals.
With the lengthening of light application time, characteristic absorption peak of the ABDA at 378nm is gradually decreased, and represents system constantly
It generates1O2。
(2) encapsulation of chemotherapeutics and pH response release test
Specific step is as follows:
The nano-carrier of 5mg/mL is mixed with 1mg/mL bortezomib (Btz) DMSO solution, concussion reaction 5h will be mixed
Liquid centrifugation, washing are three times.The nano-carrier for having loaded Btz is dispersed in the PBS buffering of different pH (pH=7.4 and pH=5.4)
In liquid, persistent oscillation at room temperature at regular intervals takes out the old PBS of 0.5mL, and with new PBS buffer solution replace from
And keeping total volume constant, UV measures the absorbance of supernatant, carries out drug by the characteristic absorption value variation of Btz at 270nm
Accumulative releasing research.
The result shows that there is a small amount of Btz to discharge under the physiological condition of pH=7.4, and under conditions of pH=5.4, chemotherapeutic
Object Btz substantially completely discharges.
(3) MTT cell activity is tested
By in HeLa cell inoculation to 96 porocyte culture plates, by the culture solution containing Btz, nano-carrier culture solution or
The culture solution for having loaded the nano-carrier of Btz is washed twice with HeLa cell co-culture 5h, PBS respectively, replaces fresh cultured
Base.Then laser (1W/cm is used220min 635nm) is irradiated, the cell after irradiation is cultivated for for 24 hours, dark group conduct pair
According to CCK-8 kit measurement cell survival rate.
The result shows that nano-carrier prepared by embodiment 2 is with tumour cell after co-culturing, and under dark condition, nanometer
Carrier does not act on tumour cell substantially, under illumination condition, generates and has cytotoxic singlet oxygen, can effectively inhibit swollen
Tumor cell proliferation.Nano-carrier is after having loaded chemotherapeutics Btz, and under the slightly sour environment of tumour, chemotherapeutics is discharged, right
Tumour cell produces more obvious inhibiting effect.
Embodiment 3
A kind of preparation method of light sensitivity DOPA amido nano-medicament carrier, comprising the following steps:
The dopamine solution of 6mmol/L is mixed with the genipin solution of 6mmol/L, in molar ratio the ratio mixing of 5 ﹕ 4,
NaOH is added and adjusts pH to 7.5,700rpm reaction for 24 hours, is centrifuged 20min under 10000rpm, is washed with deionized water three times, vacuum is dry
It is dry.
(1) photodynamic activity is tested
Use bis- (methylene) two malonic acid (ABDA) of 9,10- anthryl-as chemical probe pair1O2It is detected.Use laser
(1W/cm2It 635nm) is irradiated, surveys the absorbance of a solution at regular intervals.
With the lengthening of light application time, characteristic absorption peak of the ABDA at 378nm is gradually decreased, and represents system constantly
It generates1O2。
(2) encapsulation of chemotherapeutics and pH response release test
Specific step is as follows:
The nano-carrier of 5mg/mL is mixed with 1mg/mL adriamycin (DOX) solution, concussion reaction 5h, by mixed liquor from
The heart, washing are three times.The nano-carrier for having loaded DOX is dispersed in the PBS buffer solution of different pH (pH=7.4 and pH=5.4),
Persistent oscillation at room temperature at regular intervals takes out 0.5mL old PBS, and replaces keeping with new PBS buffer solution
Total volume is constant, and UV measures the absorbance of supernatant, carries out drug by the characteristic absorption value variation of DOX at 480nm and adds up to release
Put research.
The result shows that there is a small amount of DOX to discharge under the physiological condition of pH=7.4, and under conditions of pH=5.4, chemotherapeutic
Object DOX substantially completely discharges.
(3) MTT cell activity is tested
By in HeLa cell inoculation to 96 porocyte culture plates, by the culture solution containing DOX, nano-carrier culture solution or
The culture solution for having loaded the nano-carrier of DOX is washed twice with HeLa cell co-culture 5h, PBS respectively, replaces fresh cultured
Base.Then laser (1W/cm is used220min 635nm) is irradiated, the cell after irradiation is cultivated for for 24 hours, dark group conduct pair
According to CCK-8 kit measurement cell survival rate.
The result shows that nano-carrier prepared by embodiment 3, has carried out payload to chemotherapeutics DOX.Illumination condition
Under, photoactive nanoparticles carrier, which generates, has cytotoxic singlet oxygen, effectively inhibits tumor cell proliferation.Change having loaded
After treating drug DOX, under the slightly sour environment of tumour, DOX is discharged, apparent inhibiting effect is generated to tumour cell.
Embodiment 4
A kind of preparation method of light sensitivity DOPA amido nano-medicament carrier, comprising the following steps:
3mmol/L levodopa solution is mixed with 3mmol/L genipin solution, the ratio mixing of 1:2, is adjusted in molar ratio
Saving pH is 7.5, and room temperature shakes 500rpm reaction for 24 hours, is centrifuged 20min under 10000rpm, is washed with deionized water three times, and vacuum is dry
It is dry to get arrive nano-medicament carrier.
Light sensitivity DOPA amido nano-medicament carrier manufactured in the present embodiment, size uniformity are uniformly dispersed, having a size of 50~
120nm。
(1) photodynamic activity is tested
Use bis- (methylene) two malonic acid (ABDA) of 9,10- anthryl-as chemical probe pair1O2It is detected.Use laser
(1W/cm2It 635nm) is irradiated, surveys the absorbance of a solution at regular intervals.
With the lengthening of light application time, characteristic absorption peak of the ABDA at 378nm is gradually decreased, and represents system constantly
It generates1O2。
(2) encapsulation of chemotherapeutics and pH response release test
Specific step is as follows:
The nano-carrier of 5mg/mL is mixed with 1mg/mL adriamycin (DOX) solution, concussion reaction 5h, by mixed liquor from
The heart, washing are three times.The nano-carrier for having loaded DOX is dispersed in the PBS buffer solution of different pH (pH=7.4 and pH=5.4),
Persistent oscillation at room temperature at regular intervals takes out 0.5mL old PBS, and replaces keeping with new PBS buffer solution
Total volume is constant, and UV measures the absorbance of supernatant, carries out drug by the characteristic absorption value variation of DOX at 480nm and adds up to release
Put research.
(3) MTT cell activity is tested
By in HeLa cell inoculation to 96 porocyte culture plates, by the culture solution containing DOX, nano-carrier culture solution or
The culture solution for having loaded the nano-carrier of DOX is washed twice with HeLa cell co-culture 5h, PBS respectively, replaces fresh cultured
Base.Then laser (1W/cm is used220min 635nm) is irradiated, the cell after irradiation is cultivated for for 24 hours, dark group conduct pair
According to CCK-8 kit measurement cell survival rate.
The result shows that DOPA amido nano-medicament carrier prepared by embodiment 4, under illumination condition, can generate has
The singlet oxygen of cytotoxicity.After having loaded chemotherapeutics DOX, under the slightly sour environment of tumour, DOX is discharged, it is thin to tumour
Born of the same parents generate inhibiting effect.
Claims (9)
1. a kind of preparation method of light sensitivity DOPA amido nano-medicament carrier, which is characterized in that by dopamine or derivatives thereof
Solution is mixed with Biological cross-linker solution, and adjusting pH value is 7~8, concussion reaction, is finally centrifuged, is washed, ruler can be obtained in drying
Very little range is 30~800nm light sensitivity DOPA amido nano-medicament carrier;
Described dopamine or derivatives thereof includes dopamine, levodopa;
The Biological cross-linker includes Geniposide;
The molar ratio of described dopamine or derivatives thereof and Biological cross-linker is (0.5~5): 1.
2. a kind of preparation method of light sensitivity DOPA amido nano-medicament carrier according to claim 1, which is characterized in that
The dopamine and its derivative solution concentration are 3~50mmol/L.
3. a kind of preparation method of light sensitivity DOPA amido nano-medicament carrier according to claim 1, which is characterized in that
3~50mmol/L of the genipin solution concentration.
4. a kind of preparation method of light sensitivity DOPA amido nano-medicament carrier according to claim 1, which is characterized in that
The molar ratio of described dopamine or derivatives thereof and Biological cross-linker is specially 3~1 ﹕ 1,5 ﹕ 4 or 1 ﹕ 2.
5. a kind of preparation method of light sensitivity DOPA amido nano-medicament carrier according to claim 1, which is characterized in that
The adjusting pH value is specifically adjusted using NaOH.
6. a kind of preparation method of light sensitivity DOPA amido nano-medicament carrier according to claim 1, which is characterized in that
The concussion reaction, 500~1000rpm of revolving speed, preferably 500rpm;Reaction temperature can be 20~70 DEG C, preferably 25~40 DEG C;Institute
Stating the reaction time is 12~96h, preferably 24~36h.
7. a kind of preparation method of light sensitivity DOPA amido nano-medicament carrier according to claim 1 or 6, feature exist
In, the concussion reaction, revolving speed 500rpm;25~40 DEG C of reaction temperature;24~36h of reaction time.
8. a kind of preparation method of light sensitivity DOPA amido nano-medicament carrier according to claim 1, which is characterized in that
The centrifugation, centrifugal rotational speed are 9000~12000rpm;Centrifugation time can be 15min~30min.
9. a kind of preparation method of light sensitivity DOPA amido nano-medicament carrier according to claim 1 or 8, feature exist
In the centrifugal rotational speed is 10000rpm.
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CN113648401A (en) * | 2021-08-19 | 2021-11-16 | 沈阳药科大学 | Hybrid nano assembly for protease inhibition sensitization photodynamic therapy and preparation and application thereof |
CN113648401B (en) * | 2021-08-19 | 2023-07-04 | 沈阳药科大学 | Hybrid nano-assembly for proteasome inhibition sensitization photodynamic therapy and preparation and application thereof |
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