CN110627846B - Galactoside-tetrastyrene compound, preparation method thereof and application thereof as drug carrier - Google Patents
Galactoside-tetrastyrene compound, preparation method thereof and application thereof as drug carrier Download PDFInfo
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Abstract
The invention belongs to the technical field of chemistry, and particularly relates to a galactoside-tetrastyrene compound, a preparation method thereof and application thereof as a drug carrier. The galactoside-tetra-styrene compound takes TPE as a hydrophobic entity and galactose as a hydrophilic entity and is formed by combining triazole, the aggregation-induced emission effect of the hydrophobic entity Tetraphenylethylene (TPE) can be used for constructing the imaging of a multifunctional system, the visual drug transfer can be realized, the targeting effect of the hydrophilic entity galactose is used for realizing the targeted delivery of the drug, meanwhile, the galactoside-tetra-styrene compound can be conveniently self-assembled into uniform and firm vesicles through a dialysis method, the vesicles formed by self-assembly also have good dispersibility and good drug loading performance, the anticancer drug can have more excellent pharmacokinetic characteristics, and the galactoside-tetra-styrene compound has potential application prospects in the aspects of drug controlled release and tumor targeted therapy.
Description
Technical Field
The invention belongs to the technical field of chemistry, and particularly relates to a galactoside-tetrastyrene compound, a preparation method thereof and application thereof as a drug carrier.
Background
Chemotherapy is an indispensable method for treating cancer, but traditional chemotherapeutic drugs have poor pharmacokinetics and lack tumor targets, so that the clinical application of the traditional chemotherapeutic drugs is limited.
In order to improve the targeting and pharmacokinetic properties of chemotherapeutic drugs, nano drug carriers are widely used as Drug Delivery Systems (DDSs) to improve the therapeutic effects of chemotherapeutic drugs. For example, nano-drug carriers such as liposomes, micelles, nanogels, vesicles and inorganic materials can be passively targeted to a focus part through high permeability and retention Effect (EPR), so that the biological distribution of drugs to nonspecific cells or tissues is reduced to reduce the occurrence of side effects, and the rapid metabolism or elimination of the drugs by the body can be avoided to a certain extent.
In recent years, the application of the amphiphilic block copolymer as a drug delivery system in cancer treatment is receiving more and more extensive attention, and the amphiphilic block copolymer can self-assemble into a bilayer, a micelle or a vesicle in a selective solvent, and has the advantages of improving the stability, increasing the bioavailability, enhancing the permeability, retaining the effect and the like.
Carbohydrate compounds are involved in a variety of biological processes and are key molecules for the recognition of receptor proteins such as hormones, enzymes, toxins, lectins, antibodies, viruses and bacteria. Galectins belong to one of the lectin families, can be specifically combined with galactoside through a strict galactoside recognition domain, and because the galectins are widely expressed in solid tumor cell membranes, such as cell membranes of malignant tumors of large intestine, lung, mammary gland, pancreas, liver, thyroid gland, blood system and the like, the introduction of galactoside into an amphiphilic block copolymer is taken as a drug delivery system, and the galactoside is used for targeting the galectins, so that the improvement of the targeting property of the drugs is theoretically feasible. Meanwhile, the galactosidase has high expression in various cancer subtypes, such as malignant tumors of liver, lung, ovary and the like, so that galactoside with high expression in malignant tumors can be used for activating various galactoside drug delivery systems, and the targeting property and the pharmacokinetic performance of the drug are improved.
Disclosure of Invention
In view of the above, an object of the present invention is to provide an amphiphilic block copolymer galactoside-tetrastyrene compound (TPE-Gal) introduced with galactoside, which can be easily self-assembled into uniform and robust vesicles by dialysis, and has excellent fluorescence, targeting property and pharmacokinetic properties as a drug delivery system.
Another object of the present invention is to provide a method for preparing the galactoside-introduced amphiphilic block copolymer galactoside-tetrastyrene compound (TPE-Gal).
Still another object of the present invention is to provide use of the amphiphilic block copolymer galactoside-tetrastyrene compound (TPE-Gal) into which galactoside is introduced.
In order to achieve the purpose, the invention provides the following technical scheme:
1. the invention discloses a galactoside-tetrastyrene compound, which has the following structure:
2. the invention discloses a preparation method of the galactoside-tetrastyrene compound, and the synthetic route of the preparation method is as follows:
the preparation method comprises the following steps:
s1 preparation of Compound 1:1,2,3,4,6-penta-O-acetyl-beta-D-galactopyranose and propargyl alcohol are used as raw materials to react under the action of boron trifluoride diethyl etherate to prepare a compound 1;
s2, preparing a compound 2: 4-hydroxybenzophenone and 1,6-dibromohexane are taken as raw materials, and a mono-substitution reaction is carried out under the action of an alkaline compound to prepare a compound 2;
s3 preparation of Compound 3: reacting the compound 2 serving as a raw material under the action of zinc powder and titanium tetrachloride to obtain a compound 3;
s4, preparation of Compound 4: carrying out substitution reaction on the compound 3 serving as a raw material and an azide to obtain a compound 4;
s5, preparing a compound 5: taking a compound 1 and a compound 4 as raw materials, and reacting under the action of sodium ascorbate and copper sulfate pentahydrate to obtain a compound 5;
s6, preparing a galactoside-tetrastyrene compound TPE-Gal: the compound 5 is taken as a raw material, and acetyl protecting groups are removed under alkaline conditions to prepare the galactoside-tetrastyrene compound TPE-Gal.
3. The invention also discloses application of the galactoside-tetrastyrene compound as a drug carrier.
In the application of the galactoside-tetrastyrene compound as a drug carrier, the galactoside-tetrastyrene compound is preferably used as a drug carrier of an anti-tumor drug.
In the application of the galactoside-tetrastyrene compound as a drug carrier of an anti-tumor drug, the galactoside-tetrastyrene compound is preferably self-assembled into a vesicle serving as a load vesicle of the anti-tumor drug.
In the application of the galactoside-tetrastyrene compound self-assembled into the vesicle serving as the load vesicle of the antitumor drug, the galactoside-tetrastyrene compound is preferably prepared into the vesicle serving as the load vesicle of the adriamycin DOX.
The invention also discloses a drug delivery system containing the galactoside-tetrastyrene compound, and the drug delivery system contains the galactoside-tetrastyrene compound and an anti-tumor drug with a therapeutically effective dose.
The drug-carrying system can completely and directly consist of the galactoside-tetrastyrene compound and the drugs, can achieve the beneficial effects of the invention, but preferably, the drug-carrying system is added with pharmaceutical excipients, so that a better drug-carrying system can be obtained.
The beneficial effects of the invention are as follows: the galactoside-tetrastyrene compound is formed by combining TPE (thermoplastic elastomer) serving as a hydrophobic entity and galactose serving as a hydrophilic entity through triazole, can construct imaging of a multifunctional system by utilizing the aggregation-induced emission effect of the hydrophobic entity Tetraphenylethylene (TPE), can realize visual drug transfer, can realize targeted delivery of a drug by utilizing the targeting effect of the hydrophilic entity galactose, and meanwhile, can be conveniently self-assembled into uniform and firm vesicles through a dialysis method. The preparation method of the galactoside-tetrastyrene compound disclosed by the invention is mild in reaction conditions, and the used reagents are all common industrial reagents, so that the preparation method is suitable for large-scale industrial preparation and has good commercial application value.
Drawings
FIG. 1 shows TPE-Gal (10. Mu.M) in DMSO/H 2 A fluorescence property test result diagram in the O mixed solvent;
FIG. 2 is a diagram of the transmission electron microscope and dynamic light scattering characterization results of TPE-Gal vesicles; wherein, A is a high-resolution transmission electron microscope characterization image of the TPE-Gal vesicle, B is a particle size distribution diagram of the TPE-Gal vesicle, and C is a Zeta potential diagram of the TPE-Gal vesicle;
FIG. 3 is a TPE-Gal @ DOX drug-loaded vesicle transmission electron microscope and dynamic light scattering characterization result diagram; wherein, A is a high-resolution transmission electron microscope characterization diagram of the TPE-Gal @ DOX medicine carrying vesicle, B is a particle size distribution diagram of the TPE-Gal @ DOX medicine carrying vesicle, and C is a Zeta potential diagram of the TPE-Gal @ DOX medicine carrying vesicle;
FIG. 4 is a graph of UV absorption spectra, IR spectra, and DSC characterization results; wherein, A is an ultraviolet absorption spectrum of DOX, TPE-Gal @ DOX medicine-carrying vesicles and TPE-Gal vesicles, and B is an infrared spectrum of DOX, TPE-Gal @ DOX medicine-carrying vesicles and TPE-Gal vesicles; c is a DSC atlas of DOX, TPE-Gal @ DOX medicine carrying vesicle and TPE-Gal vesicle;
FIG. 5 is a diagram of the phagocytosis behavior of the TPE-Gal @ DOX drug-loaded vesicles by HepG2 cells and L02 cells and the control release behavior of intracellular DOX.
Detailed Description
The present invention will now be described more fully hereinafter with reference to the accompanying specific embodiments, in which some, but not all embodiments of the invention are shown. All other embodiments that can be derived by one of ordinary skill in the art from the embodiments disclosed herein are intended to be within the scope of the present invention.
EXAMPLE 1 preparation of galactoside-Tetrastyrene Compound
1. Preparation of Compound 1
1,2,3,4,6-penta-O-acetyl-beta-D-galactopyranose (2.0 mmol) is dissolved in dry dichloromethane, propargyl alcohol (3.0 mmol) is added dropwise at 0 ℃ under the protection of nitrogen, boron trifluoride ethyl ether (3.6 mmol) is then added dropwise, and the reaction is carried out at room temperature overnight. After the reaction, potassium carbonate (200 mg) was added thereto and stirred for 30 minutes to quench the reaction, followed by filtration, and the filtrate was extracted with water and methylene chloride 3 times, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The concentrate was separated by column chromatography to give the title compound 1 as a white solid in 85% yield.
1 H NMR(600MHz,CDCl 3 )δ5.40(s,1H),5.22(t,J＝9.2Hz,1H),5.06(d,J＝10.4Hz,1H),4.74(d,J＝8.4Hz,1H),4.38(s,2H),4.22-4.16(m,1H),4.14-4.11(m,1H),3.94(t,J＝6.6Hz,1H),2.46(s,1H),2.15(s,3H),2.07(s,3H),2.05(s,3H),1.99(s,3H).
2. Preparation of Compound 2
4-hydroxybenzophenone (2.52 mmol), 1,6-dibromohexane (7.56 mmol) and potassium carbonate (1.045 g) were dissolved in 15mL of acetone solution. The mixture was heated under reflux overnight, cooled to room temperature after the reaction was completed, and filtered. And (3) distilling the filtrate under reduced pressure to remove the solvent, and separating the concentrate by column chromatography to obtain the target compound 2 which is a white solid with the yield of 82%.
1 H NMR(400MHz,CDCl 3 )δ7.82(d,J＝8.8Hz,2H),7.75(d,J＝7.2Hz,1H),7.56(t,J＝7.4Hz,1H),7.47(t,J＝7.4Hz,1H),6.95(d,J＝8.8Hz,1H),4.05(t,J＝6.4Hz,1H),3.43(t,J＝6.8Hz,1H),1.82-1.92(m,4H),1.57-1.49(m,4H).
3. Preparation of Compound 3
Compound 2 (1 mmol) and zinc powder (2.2 mmol) were dissolved in 5mL of dry tetrahydrofuran, cooled to-78 deg.C, titanium tetrachloride (1.5 mmol) was added under nitrogen, and stirring was continued at-78 deg.C for 1 hour, followed by heating and refluxing overnight. And after the reaction is finished, filtering, distilling the filtrate under reduced pressure to remove the solvent, and separating the concentrate by column chromatography to obtain the target compound 3 which is a light yellow liquid with the yield of 81%.
1 H NMR(600MHz,CDCl 3 )δ7.14-6.99(m,10H),6.93-6.88(m,4H),6.64-6.59(m,4H),3.90-3.86(m,4H),3.43-3.40(m,4H),1.90-1.87(m,4H),1.75-1.73(m,4H),1.49-1.48(m,8H).
HRMS(ESI),m/z calcd.for C 38 H 43 Br 2 O 2 ([M+H]+)689.1624,found:689.1624.
4. Preparation of Compound 4
Compound 3 (0.5 mmol) was dissolved in dry DMF (10 mL), sodium azide (1.5 mmol) and ammonium chloride (0.75 mmol) were added, and the mixture was heated to 85 ℃ and stirred overnight. After the reaction is finished, pouring the reaction system into 30mL of water, extracting with ethyl acetate for three times, combining organic phases, drying with anhydrous sodium sulfate, and distilling under reduced pressure to remove the solvent. The concentrate was separated by column chromatography to give the objective compound 4 as a pale yellow liquid with a yield of 89%.
1 H NMR(400MHz,CDCl 3 )δ7.17-7.01(m,10H),6.98-6.92(m,4H),6.68-6.62(m,4H),3.93-3.87(m,4H),3.32-3.28(m,4H),1.81-1.76(m,4H),1.68-1.63(m,4H),1.52-1.45(m,8H).
HRMS(ESI),m/z calcd.for C 38 H 43 N 6 O 2 ([M+H]+)615.3442,found:615.3443.
5. Preparation of Compound 5
Compound 1 (0.8 mmol) and compound 4 (0.4 mmol) were dissolved in a mixed solvent of water and tetrahydrofuran (the volume ratio of water to tetrahydrofuran was 1,10 mL), and sodium ascorbate (0.2 mmol) and copper sulfate pentahydrate (0.4 mmol) were added and stirred at 65 ℃ for 4 hours under dark conditions. After the reaction is finished, distilling under reduced pressure to remove tetrahydrofuran, then adding ethyl acetate to extract for 3 times, combining organic phases, drying by anhydrous sodium sulfate, distilling under reduced pressure to remove the solvent, and separating the concentrate by column chromatography to obtain the target compound 5 which is light yellow oily liquid with the yield of 88%.
1 H NMR(400MHz,CDCl 3 )δ7.49(d,J＝3.5Hz,2H),7.13-6.94(m,10H),6.94-6.82(m,4H),6.57(m,4H),5.37(d,J＝2.0Hz,2H),5.27-5.13(m,2H),5.00(dd,J＝10.4,2.8Hz,2H),4.93(d,J＝12.6Hz,2H),4.78(d,J＝12.6Hz,2H),4.64(d,J＝7.8Hz,2H),4.32-4.30(m,4H),4.19-4.08(m,4H),3.93(t,J＝6.6Hz,2H),3.83(dd,J＝13.8,7.0Hz,4H),2.14(s,6H),2.05(s,6H),1.98(s,6H),1.97(s,6H),1.99-1.88(m,4H),1.72-1.67(m,4H),1.49-1.46(m,4H),1.38-1.35(m,4H).
13 C NMR(150MHz,CDCl 3 )δ170.59,170.12,169.38,169.30,157.21,144.18,143.95,139.45,136.15,132.40,131.25,127.53,126.03,122.49,113.31,99.73,72.61,72.61,71.06,68.13,67.19,62.89,61.67,50.17,30.12,28.93,26.15,25.46,20.68,20.58,20.52.
HRMS(ESI),m/z calcd.for C 72 H 86 N 6 NaO 22 ([M+Na]+)1409.5687,found:1409.5665.
6. Preparation of galactoside-tetrastyrene compound TPE-Gal
Taking the compound 5, adding 10mL of methanol into a round-bottom flask for dissolving, and dropwise adding 1mol/L sodium methoxide solution at room temperature to adjust the pH value to 8-9. After TLC monitoring raw material reaction is completed, adding acid resin to regulate pH value to be about 7, filtering, reduced pressure distillation to remove solvent, and separating concentrate by thin layer column chromatography to obtain product which is light yellow foam solid with yield of 45%.
1 H NMR(400MHz,MeOD)δ8.00(s,2H),7.14-7.02(m,6H),7.04-6.93(m,4H),6.94-6.81(m,4H),6.69-6.54(m,4H),4.96(d,J＝12.4Hz,2H),4.78(d,J＝12.4Hz,2H),4.40(t,J＝7.0Hz,4H),4.33(dd,J＝7.6,1.6Hz,2H),3.91-3.81(m,6H),3.81-3.66(m,4H),3.61-3.51(m,4H),3.4-3.44(m,2H),2.00-1.85(m,4H),1.75-1.69(m,4H),1.52-1.47(m,4H),1.39-1.34(m,4H).
13 C NMR(150MHz,MeOD)δ158.9,145.7,145.6,141.1,137.5,137.5,133.6,132.4,128.7,127.3,125.3,114.6,103.6,78.0,77.9,75.0,71.6,68.6,63.0,62.7,61.3,31.2,27.2,26.6.
HRMS(ESI),m/z calcd.for C 56 H 70 N 6 NaO 14 ([M+Na]+)1073.4842,found:1073.4833.
Example 2 preparation and Performance Studies of TPE-Gal vesicles
TPE-Gal Aggregation Induced Emission (AIE) Performance test
The AIE characteristics of TPE-Gal were studied by adding water, a poor solvent, continuously to DMSO, a good solvent. 2.6mg of galactoside-tetrastyrene compound is dissolved in 25mL of DMSO solution to prepare a 100. Mu.M stock solution. And then respectively putting 0.5mL of stock solution into a 5mL colorimetric tube, respectively adding 2.0, 1.5, 1.0, 0.5 and 0mL of DMSO solution, then adding purified water to the scale, and uniformly mixing to obtain the TPE-Gal mixed solution with the water content of 50%, 60%, 70%, 80% and 90%. Transferring the mixed solution into a quartz cuvette, measuring the fluorescence property at room temperature with the excitation wavelength lambda ex of 330nm and the scanning range of 200-600 nm, and obtaining the test result shown in figure 1.
As can be seen from FIG. 1, TPE-Gal (10. Mu.M) shows very weak fluorescence in DMSO at an excitation wavelength of 330nm, with the maximum peak usually at 390 nm. However, as the proportion of water increases, the fluorescence emission intensity significantly increases, and particularly when the proportion of water is more than 60%, the fluorescence intensity significantly increases, and the maximum emission peak widens and red-shifts to 473nm. When the water fraction reached 90%, the fluorescence intensity of TPE-Gal was more than 90-fold stronger than that of 100% DMSO. These results indicate that TPE-Gal has typical AIE characteristics, and intramolecular rotation of the tetraphenylethylene moiety is blocked, resulting in fluorescence enhancement.
Preparation and characterization of TPE-Gal vesicles
And preparing the TPE-Gal vesicle by a dialysis method. 0.35mL of the stock solution was diluted with DMSO to 1.75mL, and 1.75mL of purified water was added dropwise while stirring on a magnetic stirrer. After the addition, stirring was continued for 1 hour, and then the mixture was transferred to a dialysis bag, both ends of which were sealed, and dialyzed in 100mL of purified water. Purified water was changed every 6 hours for 24 hours of total dialysis. And (5) after dialysis, freeze-drying to obtain the TPE-Gal vesicle solid. The TPE-Gal vesicles obtained were characterized by transmission electron microscopy and Dynamic Light Scattering (DLS), and the results are shown in FIG. 2.
As shown in FIG. 2, the transmission electron microscope results show that the morphology of the TPE-Gal vesicle is smooth in surface and is in a hollow spherical shape (FIG. 2A). Dynamic Light Scattering (DLS) analysis showed that the average particle size and polydispersity index (PDI) of TPE-Gal vesicles were 157.4 ± 7.69nm and 0.074, respectively, revealing that the vesicles dispersed well in aqueous solution and no significant polymerization (fig. 2B). The Zeta potential of TPE-Gal vesicles was-25. + -. 2.3mV (FIG. 2C).
Example 3 preparation and Performance Studies of Adriamycin-loaded vesicles
1. Preparation and characterization of Adriamycin-loaded vesicles
As a novel hollow spherical vesicle, the further study on the drug bearing capacity of the vesicle is of great significance. Doxorubicin DOX is selected as a model antitumor drug, a DOX-loaded TPE-Gal vesicle (TPE-Gal @ DOX) is prepared by an ammonium sulfate gradient method, and DOX which does not enter the vesicle is removed by a dialysis method.
The preparation method comprises the following steps: a1 mM stock solution was prepared by dissolving 26mg of the galactoside-tetrastyrene compound in 25mL of DMSO solution. 0.35mL of the stock solution was diluted with DMSO to 1.75mL, and 1.75mL of ammonium sulfate solution was added dropwise while stirring on a magnetic stirrer. After the addition, stirring was continued for 1 hour, and then the mixture was transferred to a dialysis bag, both ends of which were sealed, and dialyzed in 100mL of purified water. Purified water was changed every 6 hours for 24 hours of total dialysis to obtain blank vesicles. Aqueous doxorubicin hydrochloride (5 mg/mL) was added to the blank vesicles and incubated at 50 ℃ for 3 hours with constant shaking. The unencapsulated doxorubicin was then removed by dialysis of the mixture in a dialysis bag for 24 hours. And (5) after dialysis, carrying out freeze drying to obtain the solid drug-loaded vesicle TPE-Gal @ DOX. The prepared TPE-Gal @ DOX drug-loaded vesicles were characterized by transmission electron microscopy and Dynamic Light Scattering (DLS), and the results are shown in FIG. 3.
As can be seen from FIG. 3, the TEM result shows that the drug-loaded TPE-Gal vesicles are spherical (FIG. 3A), and Dynamic Light Scattering (DLS) analysis shows that the TPE-Gal @ DOX vesicles are well dispersed in the aqueous solution, the diameter is 165.2 +/-8.31 nm (FIG. 3B), and the zeta potential is-17.1 +/-4.4 mV (FIG. 3C).
To further demonstrate the loading of DOX on vesicles and the loading capacity of vesicles, DOX, TPE-Gal vesicles and TPE-Gal @ DOX vesicles were studied using UV absorption spectroscopy and IR spectroscopy, respectively, and the results are shown in FIGS. 4A and 4B. According to the characteristic absorbance peak of DOX at 480nm, the bearing performance of the TPE-Gal @ DOX vesicle is determined. The TPE-Gal @ DOX vesicles have good DOX loading capacity, the Drug Loading Capacity (DLC) is 15.4wt%, and the Entrapment Efficiency (EE) is 88.5%. The result shows that the TPE-Gal vesicle has good drug loading capacity.
In order to further prove that the vesicles are loaded with DOX, the distribution state of the DOX in the TPE-Gal @ DOX vesicles is detected by a DSC method, and the result is shown in FIG. 4C, which strongly proves the successful preparation of the TPE-Gal @ DOX vesicles.
2. Investigation of cellular uptake and intracellular controlled release behavior
HepG2 and L02 cells are selected as model cells, and the phagocytosis of TPE-Gal @ DOX vesicles and the release condition of intracellular DOX by the cells are detected by a Confocal Laser Scanning Microscope (CLSM).
HepG2 cells were incubated with TPE-Gal @ DOX for 0.5, 1,2 hours, respectively, before imaging. In CLSM images using TPE and DOX fluorescence channels, as shown in fig. 5, the fluorescence intensity steadily increased with time, indicating that the phagocytosis of vesicles by HepG2 cells and the release of drug from TPE-gal @ DOX vesicles were successful and time-dependent. After incubation of the TPE-Gal @ DOX vesicles for 0.5h, hepG2 cells started to fluoresce significantly with TPE and DOX, and each cell showed the same fluorescence region. The DOX released from TPE-gal @ DOX vesicles resulted in overlap of TPE and DOX fluorescence, and this region of simultaneous TPE and DOX aggregation we believe corresponds to lysosomes. After incubation for 2h, the fluorescence of TPE is clearly visible in cytoplasm or lysosome and is not transferred to nucleus, which indicates that the vesicle only plays its delivery function and does not affect the anticancer effect of the drug. In the DOX fluorescence channel, DOX is released from the vesicle and transported to the nucleus, and most of DOX is located in the nucleus except for a small amount of DOX accumulated in the lysosome. However, L02 cells showed only weak DOX fluorescence, although they showed clear TPE fluorescence compared to HepG2 cells. These phenomena indicate that TPE-Gal vesicles can be efficiently taken up by cells for imaging, but show a sustained drug release pattern only in tumor cells.
In vitro evaluation shows that the self-indicated TPE-Gal vesicles can effectively load anticancer drug adriamycin (DOX). At the cellular level, TPE-gal @ DOX vesicles have a significant target effect than free DOX. The TPE-Gal @ DOX is prompted to have a strong targeted anti-tumor treatment effect, and the development of a visual drug delivery carrier in the field of tumor treatment is expected to be further promoted.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, but rather as the intention of all modifications, equivalents, improvements, and equivalents falling within the spirit and scope of the invention.
Claims (8)
1. A galactoside-tetrastyrene compound, characterized by having the structure shown below:
2. the method for preparing a galactoside-tetrastyrene compound according to claim 1, comprising the steps of:
s1 preparation of Compound 1:1,2,3,4,6-penta-O-acetyl-beta-D-galactopyranose and propargyl alcohol are used as raw materials to react under the action of boron trifluoride ethyl ether to prepare a compound 1;
s2, preparing a compound 2: 4-hydroxybenzophenone and 1,6-dibromohexane are taken as raw materials, and a mono-substitution reaction is carried out under the action of an alkaline compound to prepare a compound 2;
s3 preparation of Compound 3: taking the compound 2 as a raw material, and reacting under the action of zinc powder and titanium tetrachloride to obtain a compound 3;
s4 preparation of Compound 4: taking the compound 3 as a raw material to carry out substitution reaction with an azide compound to prepare a compound 4;
s5, preparation of Compound 5: taking a compound 1 and a compound 4 as raw materials, and reacting under the action of sodium ascorbate and copper sulfate pentahydrate to obtain a compound 5;
s6, preparing a galactoside-tetrastyrene compound TPE-Gal: removing acetyl protecting groups under alkaline conditions by taking a compound 5 as a raw material to prepare a galactoside-tetrastyrene compound TPE-Gal;
wherein, the structure of the compound 1 is as follows:
the structure of compound 2 is as follows:
the structure of compound 3 is as follows:
the structure of compound 4 is as follows:
compound 5 has the structure:
the structure of TPE-Gal is as follows:
3. use of the galactoside-tetrastyrene compound of claim 1 for the preparation of a pharmaceutical carrier.
4. The use according to claim 3, wherein the use is the use of the galactoside-tetrastyrene compound in the preparation of an antitumor drug carrier.
5. The use according to claim 4, wherein the use is the use of self-assembly vesicles of the galactoside-tetrastyrene compound in the preparation of antitumor drug-loaded vesicles.
6. The use according to claim 5, wherein the use is the use of self-assembly vesicles of the galactoside-tetrastyrene compound in the preparation of doxorubicin DOX drug-loaded vesicles.
7. A drug delivery system comprising the galactoside-tetrastyrene compound according to claim 1, wherein the drug delivery system comprises the galactoside-tetrastyrene compound and a therapeutically effective amount of an anti-tumor drug.
8. The drug delivery system of claim 7, further comprising a pharmaceutically acceptable excipient.
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