CN103920160A - Graphene/hyaluronic acid assembly taking cyclodextrin as medium and preparation method thereof - Google Patents
Graphene/hyaluronic acid assembly taking cyclodextrin as medium and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a graphene/hyaluronic acid assembly taking cyclodextrin as a medium. The graphene/hyaluronic acid assembly is a nano supermolecule assembly synthesized based on beta-cyclodextrin-modified graphene and adamantine-modified hyaluronic acid, wherein graphene is modified by beta-cyclodextrin; by virtue of strong host-guest interaction between beta-cyclodextrin and adamantine, graphene and hyaluronic acid are combined together to form the supermolecule assembly. The graphene/hyaluronic acid assembly has the advantages that the supermolecule assembly greatly improves stability and biocompatibility of the cyclodextrin-modified graphene under physiological conditions; by utilizing targeted recognition action of hyaluronic acid on tumor cells, the supermolecule assembly can selectively kill the cancer cells, and has anti-cancer activity higher than that of pure drug camptothecin; the targeted drug transmission system is simple in preparation process, easy to implement and low in material cost, and has potential application prospect in clinic treatment of cancers.
Description
Technical field
The present invention relates to Graphene/hyaluronic acid nanometer super-molecule assembling body that cancer therapy drug targeted delivery technical field, particularly a kind of cyclodextrin are medium and preparation method thereof.
Background technology
Drug loading system based on nano material, owing to having functions such as medicine payload, targeted delivery and controllable release, has important application in current nanotechnology and biomedicine field.Graphene is the nano material with two-dimension plane structure of development in recent years a kind of novelty of getting up, because it has unique engineering properties, macroscopic property, chemical property and optical property, as pharmaceutical carrier and biosensor etc., in the using value of biomedicine field, embody gradually.The surface of Graphene can interact and the many cancer therapy drug molecules with large π system of hydrophobic interaction load by π-π, as amycin and camptothecine, can effectively improve water solublity and the active anticancer of medicine.But Graphene exists unstability under physiological condition and the problems such as safety in body always.At present, by covalently bound method, some hydrophilic macromolecules are modified at and on Graphene, effectively raise its stability under physiological condition, and by the agent of further introducing targeting, reduced Graphene drug delivery system to Normocellular toxic and side effects, improved utilization ratio of drug.Hyaluronic acid is a kind of have good bio-compatibility and natural polymer of biodegradability, due to the identification ability having the hyaluronic acid binding protein of tumor cell surface overexpression (CD44 and RHAMM), become targeting agent conventional in drug delivery system.So, hyaluronic acid and Graphene are combined, bio-compatibility and the stability of Graphene not only can be significantly improved, and its target function can be given.Method with respect to the covalent modification of more complicated, supermolecule technology can make the preparation of Graphene/hyaluronic acid drug delivery system more simple, and the introducing of supermolecule biotechnology can increase the specificity of system, reduce multidrug resistance, improve clinical medicine in the bioavailability of avtive spot.
Summary of the invention
The object of the invention is for above-mentioned technical Analysis, it is Graphene/hyaluronic acid super-molecule assembling body of medium and preparation method thereof that a kind of cyclodextrin is provided, this super-molecule assembling body can targeted delivery water transport property cancer therapy drug camptothecine, and preparation method is simple, active anticancer is high, be suitable for amplifying synthetic and production application.
Technical scheme of the present invention:
Cyclodextrin is Graphene/hyaluronic acid super-molecule assembling body of medium, for based on
β-cyclodextrin modified Graphene and the synthetic nano supermolecule assembly of hyaluronic acid of diamantane (obsolete) modification, wherein
β-cyclodextrin modified Graphene, its thickness is 2.5 nm, and the graphene modified of 1 g has 0.28 g's
β-cyclodextrin ethylenediamine; Diamantane (obsolete) is modified average every 7.7 the hyaluronic acid unit of hyaluronic acid and is modified with a diamantane (obsolete) unit; This super-molecule assembling body passes through
βstrong host-guest interaction between-cyclodextrin and diamantane (obsolete), is combined together to form super-molecule assembling body by Graphene and hyaluronic acid, and its thickness is 4.5 nm, and size is 50-100 nm.
Described cyclodextrin is a preparation method for Graphene/hyaluronic acid super-molecule assembling body of medium, comprises the following steps:
(1) N-(2-aminoethyl)-1-diamantane (obsolete) Methanamide is synthetic
1) under room temperature, ethylenediamine is dissolved in Isosorbide-5-Nitrae-dioxane, then dropwise adds (Boc)
2isosorbide-5-Nitrae-dioxane solution of O, reaction 24 h, distilling under reduced pressure is except desolventizing, and the residue obtained deionized water dissolving of using, removes by filter insoluble matter, by filtrate dichloromethane extraction, collects organic facies, uses anhydrous Na
2sO
4dry, distilling under reduced pressure, except desolventizing, obtains the ethylenediamine of oily compound list Boc protection;
2) diamantane (obsolete) acyl chlorides is dissolved in dichloromethane; the dichloromethane solution that dropwise adds the ethylenediamine of triethylamine and above-mentioned single Boc protection; to under the mixed liquor room temperature obtaining, stir and spend the night, then with HCl and the NaCl solution of 0.01 mol/L, wash respectively three times, collect organic facies and use anhydrous Na
2sO
4dry, distilling under reduced pressure is except desolventizing, by gained crude product take volume ratio as 3:2 dichloromethane-ethyl acetate mixed liquor be eluant, with 200-300 order silicagel column separating-purifying, compound after purifying is dissolved in dichloromethane, the dichloromethane solution that dropwise adds trifluoroacetic acid, under room temperature, stir and spend the night, then distilling under reduced pressure is except adding the NaOH aqueous solution of 20 mL 5mol/L after desolventizing, under room temperature, stir 1 h, distilling under reduced pressure removes and anhydrates, solid chloroform extraction, the NaCl solution washing of 0.01 mol/L for extract, collects organic facies and uses anhydrous Na
2sO
4dry, distilling under reduced pressure is except desolventizing, and vacuum drying, obtains white solid product N-(2-aminoethyl)-1-diamantane (obsolete) Methanamide;
(2) diamantane (obsolete) is modified the synthetic of hyaluronic acid (HA-Ada)
1) hyaluronate sodium is dissolved in deionized water, the amount ratio of hyaluronate sodium and deionized water is 1 g:50 mL, and then the flow velocity with 1.5 times of bed volume per hour slowly flows through H
+type 001 * 7 cation exchange resin column, collects eluent, and distilling under reduced pressure, except anhydrating, makes hyaluronic acid (HA);
2) above-mentioned hyaluronic acid is dissolved in dimethyl sulfoxide (DMSO), be heated to 60 ℃, after hyaluronic acid dissolves completely, solution is cooled to room temperature, then in solution, add triethylamine and at room temperature stir 10 min, add again ethyl chloroformate, under room temperature, stir 1 h, finally add N-(2-aminoethyl)-1-diamantane (obsolete) Methanamide, under room temperature, stir 24 h, reaction finishes the rear deionized water diluting reaction solution that is 1:1 by volume ratio, solution after dilution is dialysed with the bag filter that molecular cut off is 8-14 kDa, first with 0.1 mol/L sodium chloride solution, 24 h that dialyse, then with deionized water dialysis 7 days, by dialysis solution lyophilizing, obtain diamantane (obsolete) and modify hyaluronic acid (HA-Ada),
(3) preparation of Graphene/hyaluronic acid super-molecule assembling body (GO-CD-HA) that cyclodextrin is medium
Diamantane (obsolete) is modified to hyaluronic acid (HA-Ada) to be joined in the aqueous solution of cyclodextrin modified Graphene (GO-CD), diamantane (obsolete) is modified hyaluronic acid and the concentration of cyclodextrin modified Graphene in aqueous solution is 2 mg/mL, ultrasonic half an hour under room temperature, then with deionized water by solution dilution to 0.4 mg/mL, with 0.45 μ m water film filtering, collect filtrate, the aqueous solution of Graphene/hyaluronic acid super-molecule assembling body (GO-CD-HA) that to obtain take cyclodextrin be medium.
Described ethylenediamine, (Boc)
2the mol ratio of O and Isosorbide-5-Nitrae-dioxane is 1.45 mol:0.18 mol:1L, and the amount ratio of diamantane (obsolete) acyl chlorides and dichloromethane is 0.22 mol:1L, and the ethylenediamine mol ratio of diamantane (obsolete) acyl chlorides, triethylamine and single Boc protection is 0.45:0.74: 0.45.
The amount ratio of described hyaluronic acid and dimethyl sulfoxide (DMSO) is 0.026 mol:1L, and the mol ratio of hyaluronic acid, triethylamine, ethyl chloroformate and N-(2-aminoethyl)-1-diamantane (obsolete) Methanamide is 0.026:0.13: 0.078: 0.013.
The application of Graphene/hyaluronic acid super-molecule assembling body that a kind of prepared cyclodextrin is medium, for targeted delivery hydrophobicity anticarcinogen camptothecine, load the preparation method of aqueous solution of Graphene/hyaluronic acid super-molecule assembling body (GO-CD-HA-CPT) of camptothecine as follows:
The dimethyl sulfoxide of camptothecine (DMSO) solution is added drop-wise in the GO-CD-HA solution preparing, under room temperature, stir and spend the night, under revolution 5000r/min, centrifugal 5 min are to remove insoluble camptothecine, by 0.45 μ m water film filtering for centrifugal liquid, remove insoluble solid, filtrate is with the bag filter that molecular cut off is 8-14 kDa 24 h that dialyse in deionized water, then by 0.45 μ m water film filtering for solution, collect filtrate, the aqueous solution of Graphene/hyaluronic acid super-molecule assembling body (GO-CD-HA-CPT) of camptothecine that obtained load.
The concentration of the dimethyl sulfoxide of described camptothecine (DMSO) solution is 10 mmol/mL, and the volume ratio of camptothecine solution and GO-CD-HA solution is 1:10.
Advantage of the present invention is: this super-molecule assembling body has improved stability and the bio-compatibility of cyclodextrin modified Graphene under physiological condition greatly; Utilize the targeting recognition reaction of hyaluronic acid to tumor cell, this super-molecule assembling body can optionally kill and wound cancerous cell, than simple camptothecin drug, shows higher active anticancer, and Normocellular toxic and side effects is reduced; Simple, the easy to implement and lower cost for material of the preparation technology of this targeted drug transport system has potential application prospect in the clinical treatment of cancer.
[accompanying drawing explanation]
Fig. 1 is the synthetic route chart of N-(2-aminoethyl)-1-diamantane (obsolete) Methanamide and HA-Ada.
Fig. 2 is the nuclear magnetic spectrogram of HA-Ada.
Fig. 3 is the syntheti c route schematic diagram of Graphene/hyaluronic acid super-molecule assembling body and load camptothecine thereof.
Fig. 4 is the atomic force microscope figure of GO-CD-HA and GO-CD-HA-CPT.
Fig. 5 is the cell inhibition figure of MDA-MB-231.
Fig. 6 is GO-CD-CPT and GO-CD-HA-CPT standing 10 h front and back comparison diagrams in PBS solution.
[specific embodiment]
Below by example, the present invention is described further.
Embodiment:
Cyclodextrin is Graphene/hyaluronic acid super-molecule assembling body of medium, for based on
β-cyclodextrin modified Graphene and the synthetic nano supermolecule assembly of hyaluronic acid of diamantane (obsolete) modification, wherein
β-cyclodextrin modified Graphene, its thickness is 2.5 nm, and the graphene modified of 1 g has 0.28 g's
β-cyclodextrin ethylenediamine; Diamantane (obsolete) is modified average every 7.7 the hyaluronic acid unit of hyaluronic acid and is modified with a diamantane (obsolete) unit; This super-molecule assembling body passes through
βstrong host-guest interaction between-cyclodextrin and diamantane (obsolete), is combined together to form super-molecule assembling body by Graphene and hyaluronic acid, and its thickness is 4.5 nm, and average-size size is 80 nm.
Described cyclodextrin is a preparation method for Graphene/hyaluronic acid super-molecule assembling body of medium, comprises the following steps:
(1) N-(2-aminoethyl)-1-diamantane (obsolete) Methanamide is synthetic
1) under room temperature, by 5.25 g(0.087 mol) ethylenediamine is dissolved in 30 mL Isosorbide-5-Nitrae-dioxane, then dropwise adds 30 mL (Boc)
2o2.45 g(0.011mol) Isosorbide-5-Nitrae-dioxane solution, reaction 24 h, distilling under reduced pressure is except desolventizing, and residue obtained use 50 m deionized water dissolving, remove by filter insoluble matter, and filtrate, with 50 m dichloromethane extractions, is collected to organic facies, use anhydrous Na
2sO
4dry, distilling under reduced pressure, except desolventizing, obtains the ethylenediamine of oily compound list Boc protection;
2) by 900 mg(4.5 mmol) diamantane (obsolete) acyl chlorides is dissolved in 10 mL dichloromethane, the triethylamine 0.7 mL(7.4 mmol that dropwise adds 10 mL) and the ethylenediamine 700 mg(4.5 mmol of single Boc protection) dichloromethane solution, to under the mixed liquor room temperature obtaining, stir and spend the night, then with HCl and the NaCl solution of 0.01 mol/L, wash respectively three times, collect organic facies and use anhydrous Na
2sO
4dry, distilling under reduced pressure is except desolventizing, by gained crude product take volume ratio as 3:2 dichloromethane-ethyl acetate mixed liquor be eluant, with 200 order silicagel column separating-purifyings, compound after purifying is dissolved in 50 mL dichloromethane, the dichloromethane solution containing 3.5 mL trifluoroacetic acids that dropwise adds 15 mL, under room temperature, stir and spend the night, then distilling under reduced pressure is except adding the NaOH aqueous solution of 20 mL 5mol/L after desolventizing, under room temperature, stir 1 h, distilling under reduced pressure is except anhydrating, solid chloroform extraction, the NaCl solution washing of 0.01 mol/L for extract, collect organic facies and use anhydrous Na
2sO
4dry, distilling under reduced pressure is except desolventizing, and vacuum drying, obtains white solid product N-(2-aminoethyl)-1-diamantane (obsolete) Methanamide, productive rate 90%.
Nuclear-magnetism and the mass spectral characteristi of N-prepared by detection display the present invention (2-aminoethyl)-1-diamantane (obsolete) Methanamide are as follows:
1h NMR (400 MHz, D
2o, TMS):
δ=1.66-1.79 (m, 6H), 1.82-1.93 (m, 6H), 1.99-2.09 (m, 3H), 2.82 (t, 2H), 3.29 (q, 2H), 6.10 (s, 1H). ESI-MS:m/z 223.3 [M+H]
+.
(2) diamantane (obsolete) is modified the synthetic of hyaluronic acid (HA-Ada)
1) 1 g hyaluronate sodium is dissolved in 50 mL deionized waters, with the flow velocity of 1.5 times of bed volume per hour, slowly flows through H
+type 001 * 7 cation exchange resin column, collects 150 mL eluents, and distilling under reduced pressure, except anhydrating, makes hyaluronic acid (HA);
2) by above-mentioned 500 mg(1.32 mmol) hyaluronic acid is dissolved in 50 mL dimethyl sulfoxide (DMSO), be heated to 60 ℃, after hyaluronic acid dissolves completely, solution is cooled to room temperature, then in solution, add 0.92 mL(6.6 mmol) triethylamine at room temperature stir 10 min, add again 0.377 mL(3.96 mmol) ethyl chloroformate, under room temperature, stir 1 h, finally add 146.6 mg(0.66 mmol) N-(2-aminoethyl)-1-diamantane (obsolete) Methanamide, under room temperature, stir 24 h, reaction finishes rear use 50 mL deionized water diluting reaction solution, solution after dilution is dialysed with the bag filter that molecular cut off is 8-14 kDa, first with 0.1 mol/L sodium chloride solution, 24 h that dialyse, then with deionized water dialysis 7 days, by dialysis solution lyophilizing, obtain diamantane (obsolete) and modify hyaluronic acid (HA-Ada),
Fig. 1 is the synthetic route chart of N-(2-aminoethyl)-1-diamantane (obsolete) Methanamide and HA-Ada, the nuclear magnetic spectrogram that Fig. 2 is HA-Ada.
Detection display: the diamantane (obsolete) of preparation is modified hyaluronic nuclear-magnetism and characterized as follows:
1h NMR (400 MHz, D
2o, TMS):
δ=1.51-1.75 (m, 1.61H), 3.05-3.99 (m, 10.62H), 4.24-4.63 (m, 2H).It is 13% that the degree of modification of diamantane (obsolete) calculates according to the nuclear-magnetism peak integral area ratio of hydrogen (δ=1.50-1.85,12H) on two hydrogen (δ=4.26-4.62,2H) on the connected methylene of hydroxyl on hyaluronic acid skeleton and six methylene of diamantane (obsolete).
(3) preparation of Graphene/hyaluronic acid super-molecule assembling body (GO-CD-HA) that cyclodextrin is medium
10 mg diamantane (obsolete) are modified to hyaluronic acids (HA-Ada) to be joined in the aqueous solution of cyclodextrin modified Graphene (GO-CD) that 5 mL, concentration are 2 mg/mL, ultrasonic half an hour under room temperature, then with deionized water by solution dilution to 0.4 mg/mL, with 0.45 μ m water film filtering, collect filtrate, the aqueous solution of Graphene/hyaluronic acid super-molecule assembling body (GO-CD-HA) that to obtain take cyclodextrin be medium.
Prepared cyclodextrin is the application of Graphene/hyaluronic acid super-molecule assembling body of medium, for load hydrophobicity anticarcinogen camptothecine, load the preparation method of aqueous solution of Graphene/hyaluronic acid super-molecule assembling body (GO-CD-HA-CPT) of camptothecine as follows:
By 3.5 mg(10 mM) camptothecine is dissolved in 1 mL dimethyl sulfoxide (DMSO), this solution is added drop-wise in the GO-CD-HA solution preparing, under room temperature, stir and spend the night, under revolution 5000r/min, centrifugal 5 min are to remove insoluble camptothecine, by 0.45 μ m water film filtering for centrifugal liquid, remove insoluble solid, filtrate is with the bag filter that molecular cut off is 8-14 kDa 24 h that dialyse in deionized water, then by 0.45 μ m water film filtering for solution, collect filtrate, the aqueous solution of Graphene/hyaluronic acid super-molecule assembling body (GO-CD-HA-CPT) of camptothecine that obtained load.
Fig. 3 is the syntheti c route schematic diagram of Graphene/hyaluronic acid super-molecule assembling body and load camptothecine thereof, and Fig. 4 is GO-CD-HA(a) and atomic force microscope figure GO-CD-HA-CPT(b).
Detection display: Graphene/hyaluronic acid super-molecule assembling body that the cyclodextrin of preparation is medium is 3.3% to the load factor of camptothecine.
Concrete effect of the present invention is as follows:
MDA-MB-231 mankind mastopathy cell is cultivated in the DMEM culture medium that contains 10% hyclone, be then layered in (every hole 100 μ L culture medium, 4000 cells) in 96 orifice plates, under the carbon dioxide conditions of 37 ° of C and 4%, cultivate 24 hours.Then respectively to the aqueous solution ([CPT]=1 μ M in culture medium) that adds CPT, GO-CD-HA, the excessive HA of GO-CD-HA-CPT, GO-CD-HA-CPT+ and five samples of GO-CD-CPT in cell culture medium, cultivate after 24 hours and 48 hours, with mtt assay, calculate the growth inhibition ratio of cell.Experimental result shows, as shown in Figure 5, assembly GO-CD-HA is totally nontoxic; GO-CD-HA-CPT has shown than the better active anticancer of simple camptothecin drug, and cell surface CD44 receptor by excessive HA in conjunction with after, the active anticancer of GO-CD-HA-CPT reduces, and has proved that GO-CD-HA-CPT has targeting to tumor cell.As shown in Figure 6, GO-CD-CPT easy coagulation under physiological condition, its 24 hours are suitable with 48 hours anticancer effects, illustrate to be subject to the impact of coagulation and to have lost lasting active anticancer.So the anticancer effect of GO-CD-HA-CPT is optimum.
Claims (6)
1. Graphene/hyaluronic acid super-molecule assembling body that cyclodextrin is medium, is characterized in that: for based on
β-cyclodextrin modified Graphene and the synthetic nano supermolecule assembly of hyaluronic acid of diamantane (obsolete) modification, wherein
β-cyclodextrin modified Graphene, its thickness is 2.5 nm, and the graphene modified of 1 g has 0.28 g's
β-cyclodextrin ethylenediamine; Diamantane (obsolete) is modified average every 7.7 the hyaluronic acid unit of hyaluronic acid and is modified with a diamantane (obsolete) unit; This super-molecule assembling body passes through
βstrong host-guest interaction between-cyclodextrin and diamantane (obsolete), is combined together to form super-molecule assembling body by Graphene and hyaluronic acid, and its thickness is 4.5 nm, and size is 50-100 nm.
2. a preparation method for Graphene/hyaluronic acid super-molecule assembling body that cyclodextrin is medium as claimed in claim 1, is characterized in that comprising the following steps:
(1) N-(2-aminoethyl)-1-diamantane (obsolete) Methanamide is synthetic
1) under room temperature, ethylenediamine is dissolved in Isosorbide-5-Nitrae-dioxane, then dropwise adds (Boc)
2isosorbide-5-Nitrae-dioxane solution of O, reaction 24 h, distilling under reduced pressure is except desolventizing, and the residue obtained deionized water dissolving of using, removes by filter insoluble matter, by filtrate dichloromethane extraction, collects organic facies, uses anhydrous Na
2sO
4dry, distilling under reduced pressure, except desolventizing, obtains the ethylenediamine of oily compound list Boc protection;
2) diamantane (obsolete) acyl chlorides is dissolved in dichloromethane; the dichloromethane solution that dropwise adds the ethylenediamine of triethylamine and above-mentioned single Boc protection; to under the mixed liquor room temperature obtaining, stir and spend the night, then with HCl and the NaCl solution of 0.01 mol/L, wash respectively three times, collect organic facies and use anhydrous Na
2sO
4dry, distilling under reduced pressure is except desolventizing, by gained crude product take volume ratio as 3:2 dichloromethane-ethyl acetate mixed liquor be eluant, with 200-300 order silicagel column separating-purifying, compound after purifying is dissolved in dichloromethane, the dichloromethane solution that dropwise adds trifluoroacetic acid, under room temperature, stir and spend the night, then distilling under reduced pressure is except adding the NaOH aqueous solution of 20 mL 5mol/L after desolventizing, under room temperature, stir 1 h, distilling under reduced pressure removes and anhydrates, solid chloroform extraction, the NaCl solution washing of 0.01 mol/L for extract, collects organic facies and uses anhydrous Na
2sO
4dry, distilling under reduced pressure is except desolventizing, and vacuum drying, obtains white solid product N-(2-aminoethyl)-1-diamantane (obsolete) Methanamide;
(2) diamantane (obsolete) is modified the synthetic of hyaluronic acid (HA-Ada)
1) hyaluronate sodium is dissolved in deionized water, the amount ratio of hyaluronate sodium and deionized water is 1 g:50 mL, and then the flow velocity with 1.5 times of bed volume per hour slowly flows through H
+type 001 * 7 cation exchange resin column, collects eluent, and distilling under reduced pressure, except anhydrating, makes hyaluronic acid (HA);
2) above-mentioned hyaluronic acid is dissolved in dimethyl sulfoxide (DMSO), be heated to 60 ℃, after hyaluronic acid dissolves completely, solution is cooled to room temperature, then in solution, add triethylamine and at room temperature stir 10 min, add again ethyl chloroformate, under room temperature, stir 1 h, finally add N-(2-aminoethyl)-1-diamantane (obsolete) Methanamide, under room temperature, stir 24 h, reaction finishes the rear deionized water diluting reaction solution that is 1:1 by volume ratio, solution after dilution is dialysed with the bag filter that molecular cut off is 8-14 kDa, first with 0.1 mol/L sodium chloride solution, 24 h that dialyse, then with deionized water dialysis 7 days, by dialysis solution lyophilizing, obtain diamantane (obsolete) and modify hyaluronic acid (HA-Ada),
(3) preparation of Graphene/hyaluronic acid super-molecule assembling body (GO-CD-HA) that cyclodextrin is medium
Diamantane (obsolete) is modified to hyaluronic acid (HA-Ada) to be joined in the aqueous solution of cyclodextrin modified Graphene (GO-CD), diamantane (obsolete) is modified hyaluronic acid and the concentration of cyclodextrin modified Graphene in aqueous solution is 2 mg/mL, ultrasonic half an hour under room temperature, then with deionized water by solution dilution to 0.4 mg/mL, with 0.45 μ m water film filtering, collect filtrate, the aqueous solution of Graphene/hyaluronic acid super-molecule assembling body (GO-CD-HA) that to obtain take cyclodextrin be medium.
3. the preparation method of Graphene/hyaluronic acid super-molecule assembling body that cyclodextrin is medium according to claim 2, is characterized in that: described ethylenediamine, (Boc)
2the mol ratio of O and Isosorbide-5-Nitrae-dioxane is 1.45 mol:0.18 mol:1L, and the amount ratio of diamantane (obsolete) acyl chlorides and dichloromethane is 0.22 mol:1L, and the ethylenediamine mol ratio of diamantane (obsolete) acyl chlorides, triethylamine and single Boc protection is 0.45:0.74: 0.45.
4. the preparation method of Graphene/hyaluronic acid super-molecule assembling body that cyclodextrin is medium according to claim 2, it is characterized in that: the amount ratio of described hyaluronic acid and dimethyl sulfoxide (DMSO) is 0.026 mol:1L, the mol ratio of hyaluronic acid, triethylamine, ethyl chloroformate and N-(2-aminoethyl)-1-diamantane (obsolete) Methanamide is 0.026:0.13: 0.078: 0.013.
5. the application of Graphene/hyaluronic acid super-molecule assembling body that cyclodextrin is medium as claimed in claim 1, it is characterized in that: for targeted delivery hydrophobicity anticarcinogen camptothecine, load the preparation method of aqueous solution of Graphene/hyaluronic acid super-molecule assembling body (GO-CD-HA-CPT) of camptothecine as follows:
The dimethyl sulfoxide of camptothecine (DMSO) solution is added drop-wise in the GO-CD-HA solution preparing, under room temperature, stir and spend the night, under revolution 5000r/min, centrifugal 5 min are to remove insoluble camptothecine, by 0.45 μ m water film filtering for centrifugal liquid, remove insoluble solid, filtrate is with the bag filter that molecular cut off is 8-14 kDa 24 h that dialyse in deionized water, then by 0.45 μ m water film filtering for solution, collect filtrate, the aqueous solution of Graphene/hyaluronic acid super-molecule assembling body (GO-CD-HA-CPT) of camptothecine that obtained load.
6. the application of Graphene/hyaluronic acid super-molecule assembling body that cyclodextrin is medium according to claim 5, it is characterized in that: the concentration of the dimethyl sulfoxide of described camptothecine (DMSO) solution is 10 mmol/mL, and the volume ratio of camptothecine solution and GO-CD-HA solution is 1:10.
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