CN113499312A - Supramolecular core-shell compound, supramolecular drug-loaded core-shell compound, and preparation methods and applications of supramolecular core-shell compound and supramolecular drug-loaded core-shell compound - Google Patents
Supramolecular core-shell compound, supramolecular drug-loaded core-shell compound, and preparation methods and applications of supramolecular core-shell compound and supramolecular drug-loaded core-shell compound Download PDFInfo
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Abstract
The invention discloses a supramolecular core-shell compound, a preparation method thereof, a supramolecular drug-loaded core-shell compound, a preparation method and application thereof, wherein a water-soluble column [5]]Aromatic hydrocarbon (WP5) is used as a host, amphiphilic aniline Tetramer (TAPEG) modified by polyethylene glycol chain segments is used as a guest molecule, and the host-guest recognition interaction between the host and the guest is utilized to form the supramolecular core-shell complex with photo-thermal properties through self-assembly. Supermolecule core-shell composite in schemeThe core of the product is hydrophobic, the shell layer is hydrophilic, the biocompatibility is good, the hydrophobic core is loaded with anticancer drug adriamycin (DOX), under the condition of micro acid of tumor cells, the structure is disintegrated, and the drug is released, thereby achieving the effect of chemotherapy treatment; the constructed supramolecular core-shell compound has better photo-thermal performance and low laser power density (1.0W/cm) in a near-infrared two-region2) Under irradiation, the chemical-photothermal combined tumor treatment is realized, and the application prospect is good in clinic.
Description
Technical Field
The invention belongs to the technical field of nano-medicine, and particularly relates to a supramolecular core-shell compound, a supramolecular drug-loaded core-shell compound, and preparation methods and applications of the supramolecular core-shell compound and the supramolecular drug-loaded core-shell compound.
Background
In contemporary society, malignant tumors are increasingly harmful to human life and health due to various exogenous and endogenous factors. The treatment means for malignant tumor is still mainly surgical treatment, radiotherapy and chemical drug therapy, but the traditional drug therapy also brings inevitable side effects to human body while treating malignant tumor due to poor drug targeting. The supermolecule nucleocapsid compound with pH stimulation responsiveness can entrap the anticancer drug in the core and release the anticancer drug in the acidic microenvironment of tumor, thereby reducing the toxic and side effects of the drug. Photothermal therapy, as an emerging therapeutic method in recent years, has obvious advantages in that cancer cells are heated and necrotized without damaging normal tissues by irradiating a tumor region with laser light to cause local high temperature. The laser of the second infrared light area biological window (1064nm) has larger allowable exposure, lower energy and stronger penetrating power. By combining chemotherapy with photothermal therapy, i.e., combination therapy, the use of anticancer drugs can be reduced to reduce toxic side effects and increase efficacy.
Applicants utilized a sodium decacarboxylate-modified column [5] in previous work (CN110934830A)]The host-guest interaction between arene (WP5) and aniline tetramer (G) is realized by including G in hydrophobic WP5 cavity through a hydrophobic cavity provided by WP5, so that a supramolecular vesicle is constructed. The vesicle has a bilayer structure, and can be used for loading anticancer drug adriamycin (DOX), and can be rapidly released in a tumor environment. Under the irradiation of near infrared laser, it can be used as tumorA tumor photothermal therapeutic agent can be used for synergistic treatment of tumor. However, the guest molecule G for constructing the supramolecular vesicle has poor water solubility and low solubility in water, so that an organic solvent is needed in the process of preparing the supramolecular vesicle, and the preparation process is slightly complicated. And the supramolecular vesicles explore the photothermal effect in the near-infrared region, but still use high laser power density (3.0W/cm)2)。
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a composite with a supermolecular core-shell structure, which has good biocompatibility, can utilize hydrophobic cores to load adriamycin, and can realize the removal of tumors under the low laser power density of a near-infrared region II.
In order to achieve the purpose, the invention provides the following technical scheme:
in a first aspect, a method for preparing a supramolecular core-shell complex is provided, which includes:
dissolving the column [5] arene modified by sodium decacarboxylate in water, and adjusting the pH to 5-7 by using a buffer solution to obtain an aqueous solution of the column [5] arene modified by sodium decacarboxylate;
dissolving amphiphilic aniline tetramer into the column [5]]Carrying out ultrasonic treatment on the aromatic hydrocarbon aqueous solution to fully mix the aromatic hydrocarbon aqueous solution, and adjusting the pH of the mixed solution to 7-8 by using a buffer solution to obtain a supermolecule core-shell compound aqueous solution; wherein the amphiphilic aniline tetramer has the following molecular structural formula:
wherein n is an integer of 8-16.
In the above scheme, the molar ratio of the amphiphilic aniline tetramer to the sodium decacarboxylate-modified column [5] arene is preferably 1: 1.
In a second aspect, there is provided an aqueous solution of supramolecular core-shell complexes prepared by the above-described preparation method.
And the third aspect provides a preparation method of the supramolecular drug-loaded core-shell compound, which comprises the steps of adding a set amount of anticancer drugs into the supramolecular core-shell compound aqueous solution, mechanically stirring to enable the anticancer drugs to be loaded into the hydrophobic core of the supramolecular core-shell compound to obtain the supramolecular drug-loaded core-shell compound solution, and removing the unencapsulated anticancer drugs through a dialysis method to obtain the supramolecular drug-loaded core-shell compound solution.
In the above scheme, the anticancer drug is preferably doxorubicin.
In the above scheme, the molar ratio of the anticancer drug to the supramolecular core-shell complex is preferably 1: 2.
in a fourth aspect, a supramolecular drug-loaded core-shell complex prepared by the preparation method is provided.
The invention further provides an application of the supramolecular drug-loaded core-shell complex in preparation of anti-tumor drugs.
Compared with the prior art, the invention has the beneficial effects that:
1. the composite assembly structure prepared by the invention is a supermolecule core-shell structure, the water solubility of the composite assembly structure is effectively increased, the hydrophobic property of the aniline tetramer is kept, and the supermolecule composite can be obtained by directly using an aqueous solution in the preparation process, so that the use of an organic solvent is reduced; because of good biocompatibility and difficult elimination by an immune system, the nucleocapsid assembly has long blood circulation time and enhanced enrichment function in a tumor part; the supramolecular core-shell compound has a lower laser power density of 1.0W/cm2The product has high photothermal conversion efficiency eta of 60.16%, and has photothermal conversion ability and no toxic side effect.
2. The hydrophobic core of the supermolecule core-shell compound can be used for efficiently encapsulating the anticancer drug, the supermolecule core-shell compound has stable appearance under normal physiological pH of a human body, but the core-shell structure is disintegrated into small micelles under the tumor subacid environment, and the drug is released from the core; therefore, the chemical drug treatment and the photothermal treatment are combined, the two have a synergistic effect, and the combined treatment has a better tumor treatment effect. The near-infrared two-region laser breaks through the current situation that most of the existing photo-thermal materials are limited to be irradiated by near-infrared first-region laser and near-infrared second-region high laser density, realizes effective treatment on tumors under the near-infrared second-region low laser density, has the advantages of strong penetrating power, low energy and the like, and has good clinical application and prospect.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings needed in the description of the embodiments or the prior art will be briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained according to the drawings without creative efforts for those skilled in the art.
Fig. 1 is a TEM image of supramolecular core-shell complexes of example 1 of the invention.
FIG. 2 is a temperature rise curve diagram of the supramolecular core-shell complex with different pH values and TAPEG in example 1 of the present invention under irradiation of laser with the same power density of 1064 nm.
Fig. 3 is a graph of temperature rise of supramolecular vesicles at different laser densities.
FIG. 4 is a diagram showing the photo-thermal properties of supramolecular core-shell complexes and supramolecular vesicles (a, 1.0W/cm)2At laser power density
Photothermal profile for one cooling cycle; b. a negative-value point diagram of the cooling time versus the natural logarithm of the thermal drive constant (θ) of diagram a; c. 3.0W/cm2At laser power density
Photothermal profile for one cooling cycle; d. negative-valued plot of cooling time versus the natural logarithm of the thermal drive constant (θ) for plot c).
Fig. 5 is a graph of the results of toxicity experiments on normal cells (L02) and mouse colon cancer cells (CT26) with different relative concentrations of TAPEG of supramolecular nucleocapsid complexes.
FIG. 6 is a confocal fluorescence microscope of supramolecular drug-loaded nucleocapsid complexes.
FIG. 7 is a graph showing the release profile of supramolecular drug-loaded core-shell complexes under different pH and 1064nm laser irradiation conditions.
FIG. 8 is an infrared thermography of tumor sites in mice irradiated with 1064nm laser for 10min (1.0W/cm2) by supramolecular drug-loaded nucleocapsid complexes.
Figure 9 is a graph of the relative tumor volume over time for each group of mice during treatment in example 3.
FIG. 10 is a graph showing the change of body weight with time of each group of mice during the treatment in example 3.
FIG. 11 is a graph showing the results of tumor imaging and in vivo imaging of mice in each group after the treatment in example 3 was completed.
FIG. 12 is a graph showing the results of tumor mass in each group of mice after the treatment in example 3 was completed.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the accompanying drawings, and it should be understood that the described embodiments are some, but not all embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
In addition, the technical features involved in the different embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The chemical reagents used in this case are commercially available without specific mention, wherein the column [5] arene (WP5) modified with sodium decacarboxylate is prepared according to the document J.Am.chem.Soc.2013,135,4, 1570-1576. The preparation method of the amphiphilic aniline Tetramer (TAPEG) modified by polyethylene glycol comprises the following steps:
to a suspension of NaH (0.43g, 60% in mineral oil, 107.4mmol) in anhydrous THF (20mL) under argon protection at 0 deg.C was added polyethylene glycol monomethyl ether (M)W550,3.938g,7.16 mmol) in THF (8mL) and stirred at 0 ℃ for 30 min; tert-butyl bromoacetate (4.19 g, 2.148mmol) was added and stirred at 25 ℃ for 24 hours; after subsequent quenching with water, the resulting mixture was extracted with ethyl acetate and the combined organic layers were dried over anhydrous sodium sulfate, concentrated in vacuo and purified by flash chromatography on silica gel (DCM: MeOH ═ 20: 1) to give the product as a pale yellow color.
A solution of the above pale yellow product (1.2g, 1.85mmol), anisole (0.4mL, 3.69mmol) and trifluoroacetic acid (2.75mL, 37.01mmol) in DCM (15mL) was stirred at 25 ℃ for 4 h. After concentration in vacuo, the residue was dissolved in ether, washed with water, the aqueous layer was collected and extracted with DCM, and the organic layers were combined and washed with anhydrous Na2SO4Dried and concentrated in vacuo to give a colorless oil.
Dissolving 0.5mmol of colorless oily product in 10mL of dichloromethane under the protection of argon, adding a catalytic amount of DMF, adding 0.2mL (2.5mmol) of oxalyl chloride at 0 ℃, stirring for half an hour, removing the ice bath, stirring at room temperature for 0.5h, refluxing for 0.5h, cooling to room temperature, performing rotary evaporation under vacuum, dissolving in dichloromethane again, performing vacuum concentration, and repeating for three times. Aniline tetramer (0.183g,0.5mmol) was dissolved in dichloromethane (10 mL), and the colorless oily product obtained in one step was added dropwise thereto at 0 ℃ with N, N-diisopropylethylamine (0.2mL,1mmol), stirred for half an hour, and stirred overnight with the ice-bath removed. The resulting mixture was extracted with water (10mL, 3 times). The combined organic layers were dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by flash chromatography on silica gel (DCM: MeOH ═ 20: 1) to give a purple oil, a polyethylene glycol-modified amphiphilic aniline tetramer of formula
Example 1: preparation of supramolecular core-shell complexes
7.6mg of WP5 was dissolved in 10mL of ultrapure water in a sample bottle, and the pH was adjusted to 6.8 by adding a buffer solution. Adding 5.0mg TAPEG directly into the above WP5 water solution, ultrasonic treating for 10min to mix thoroughly, adding PBS buffer solution to adjust pH to 7.4 to obtain
Aqueous solution of supramolecular core-shell complexes.
1-1, microstructure of supramolecular core-shell complexes
From the transmission electron micrograph, as shown in FIG. 1, it can be seen that
The aggregate of (2) is a regular core-shell structure, the aniline tetramer part of TAPEG enters a hydrophobic cavity microenvironment of WP5 to obtain a host-guest compound, the obtained compound has the characteristics of a bola type surfactant due to hydrophilicity at two ends and hydrophobicity in the middle, the compound surfactant can form micelles under certain conditions, and the obtained micelles can be further stacked into an assembly body with larger size by the strong pi-pi stacking effect and the hydrophobic effect of the aniline tetramer part of TAPEG. In the process of multi-micelle aggregation, because the micelles are tightly packed inside the assembly, a large hydrophobic core region can be formed, and because water molecules are embedded outside the assembly close to a water layer, the micelles are loosely packed, so that a shell structure is presented. According to the scheme, the water solubility of the aniline tetramer is effectively improved by grafting the polyethylene glycol chain segment on the p-aniline tetramer molecule, the hydrophobic property of the aniline tetramer is kept, the supramolecular compound can be obtained by directly using an aqueous solution in the preparation process, and the use of an organic solvent is reduced.
The construction of the core-shell assembly body enables the aniline tetramer segment to be in a double hydrophobic environment, and the specific expression is as follows: 1. Due to host-guest action, aniline tetramer part of TAPEG is embedded into hydrophobic cavity of WP 5; 2. amphiphilic aniline tetramer TAPEG and sodium decacarboxylate modified column [5]]Complexes formed with aromatic hydrocarbons WP5
Close packing to form a hydrophobic core; the construction of the double hydrophobic environment enhances the stability of TAPEG free radicals and the corresponding photothermal conversion efficiency, so that the TAPEG modified photothermal conversion material has higher photothermal conversion efficiency under low laser power density.
1-2 photo-thermal properties of supramolecular core-shell complexes
According to the preparation method, the pH of the aqueous solution is adjusted to 7.4, 6.5 and 5.5 by using PBS buffer solution, 3mL of the prepared supramolecular core-shell complex solutions with three different pH values are respectively added into a cuvette, the cuvette is irradiated by a 1064nm laser, and the laser power density is 1.0W/cm2By using thermoelectricityThe temperature change within 10min was measured with an even thermometer. As shown in fig. 2, the temperature of the supramolecular core-shell solution is obviously increased within 10min of laser irradiation, and the temperature is more obviously increased in an acidic environment; illustrating the supramolecular core-shell complex
The photo-thermal performance is good even under the lower laser power density under the irradiation of near-infrared two-zone laser. FIG. 3 shows supramolecular vesicles obtained from the previous work (CN110934830A)
The laser power density is 1.0-3.0W/cm2Temperature rise profile at low laser power density of 1.0W/cm2The temperature rise of the supramolecular core-shell polymerization solution is higher.
Irradiation with a 1064nm laser for comparison
(pH 7.4) at 1.0W/cm2Laser power density and
(pH 7.4) at 3.0W/cm2Photothermal conversion efficiency (η) at laser power density. The photothermal curves of one cooling cycle are shown in fig. 4(a) and 4(c), respectively, and the graphs (b) and (d) are obtained from fig. 4(a) and 4(c), respectively, and thus calculated
(pH 7.4) at 1.0W/cm2Eta at laser power density of 60.16%, and
(pH 7.4) at 3.0W/cm2η at laser power density was 31.20%. The method further proves that the supramolecular composite with the core-shell structure still has higher photo-thermal conversion efficiency under lower laser work near-infrared power density than the supramolecular composite with the vesicle structure, and breaks through the defect that the photo-thermal material is mostly limited in one region at presentLaser and near infrared under high laser density irradiation.
1-3 cytotoxicity assays of supramolecular nucleocapsid complexes
The cytotoxicity of supramolecular nucleocapsid complex and TAPEG was evaluated by CCK-8 method, and L02 cell (human hepatocyte) and CT26 cell (mouse colon cancer cell) were administered at 1X 10 per well4The density of individual cells was seeded in 96-well plates at 37 ℃ with 5% CO2The culture was carried out for 24 hours. Then, cells were incubated with different concentrations (10, 25, 50, 80, 100. mu.g/mL) of supramolecular nucleocapsid complex and TAPEG (37 ℃, 24 hours), respectively. Finally, CCK-8 solution was added to each well and incubated for 4 h. Absorbance at 450nm was measured using a microplate reader.
As shown in FIG. 5, it can be seen from the cytotoxicity experiment that the survival rate of the human normal cell L02 is still high even at a higher concentration, which can reach more than 80%, and the cell death rate is higher after the cell is incubated with the mouse colon cancer cell CT 26. The supramolecular nucleocapsid compound has targeted selective toxicity for treating the tumor and has good biocompatibility to normal cells.
Example 2: preparation of supramolecular drug-loaded core-shell complex
10mL of the solution prepared in example 1 was taken
An aqueous solution of supramolecular core-shell complexes (pH 7.4) comprising an anti-cancer drug in a molar ratio of supramolecular core-shell complexes of 1:2 a certain amount of Doxorubicin (DOX) is weighed out and added to the supramolecular core-shell complex solution, and the mixture is stirred for one day to be loaded into the core of the supramolecular core-shell complex. Dialyzing the prepared supermolecule drug-loaded core-shell complex solution by using a dialysis bag with the molecular weight cutoff of 14000, removing the drugs which are not wrapped in the complex, regularly replacing the aqueous solution outside the dialysis bag, and detecting the fluorescence intensity until DOX is not detected in the solution outside the dialysis bag, thus obtaining the supermolecule drug-loaded core-shell complex.
After the hydrophobic doxorubicin emitting red fluorescence is loaded on the obtained core-shell assembly, the hydrophobic doxorubicin can be seen to be in the core position through a laser confocal microscope (fig. 6), so that the core of the obtained assembly is further confirmed to be hydrophobic, and the shell layer is hydrophilic.
Drug-loading performance of 2-1 supermolecule drug-loading core-shell compound
A "fluorescence intensity-concentration" standard curve at 592nm from the characteristic DOX fluorescence emission peak in terms of the measured fluorescence intensity (pure water: y ═ 2.005X 10)8x+0.1507,x＝2.0×10-7～8.0×10-7mol/L) calculating the total amount of the released free adriamycin, thereby calculating the drug loading rate (mass of the loaded drug/mass of the material) and the encapsulation rate (mass of the loaded drug/total drug input amount) of the loaded drug. The finally calculated drug loading rate and encapsulation rate are 12.0 percent and 96.6 percent respectively, which indicates that the supramolecular core-shell compound is a good carrier of the anticancer drug adriamycin.
2-2 supramolecular drug-loaded core-shell complex drug release
1) Drug release behavior at different pH conditions
3mL of the supramolecular drug-loaded core-shell complex aqueous solution prepared in example 2 was added to a dialysis bag and immersed in a centrifuge tube containing 30mL of PBS buffer solution selected from 0.1M phosphate buffered saline solution with pH 7.4, pH 6.5 and pH 5.5 to simulate the normal physiological environment of human body, the slightly acidic environment of tumor and the pH environment of cell lysosome.
Placing the centrifuge tube into a constant temperature shaking table (37 ℃, 118rpm) for shaking, taking 3mL of solution out of the centrifuge tube at regular intervals, measuring the fluorescence intensity of DOX at 592nm by using a fluorescence spectrometer, and according to the measured fluorescence intensity, obtaining a standard curve of fluorescence intensity-concentration at 592nm of a characteristic peak of DOX fluorescence emission, wherein standard equations under three pH values are respectively as follows:
pH＝5.5:y＝2.414×108x-75.44；
pH＝6.5:y＝2.092×108x-80.62；
pH＝7.4:y＝1.844×108x-75.14；
wherein x is 2.0 × 10-7～1.0×10-5mol/L, calculating the concentration of the released medicine, and further obtaining the chemotherapeutic medicineThe release rate of the substance as a function of time is shown in FIG. 7(a), from which it can be seen that the drug is released more rapidly and in greater amounts at acidic pH compared to normal physiological conditions.
2) Release behavior of drug under 1064nm laser irradiation:
the experiment was performed in 0.1M phosphate buffered saline at pH 6.5, irradiated with a laser at 1064nm to simulate photothermal treatment of the tumor site. 3mL of supramolecular drug-loaded nucleocapsid complex aqueous solution was added to the dialysis bag and immersed in a centrifuge tube containing 30mL of PBS buffer (pH 6.5). The tube was shaken in a constant temperature shaker (37 ℃ C.; 118rpm) and then irradiated with laser at 1064nm (continuous irradiation for 15min, pause for 15min, cycle for 2 times, continuous irradiation for 30min, pause for 30min, cycle for 2 times, total time 4 h). Taking out 3mL of solution from the centrifuge tube at regular intervals, measuring the ultraviolet absorption intensity of the Doxorubicin (DOX) at 592nm by using a fluorescence spectrometer, pouring the solution back into the mother solution, continuing to oscillate, and obtaining a standard curve of 'fluorescence intensity-concentration' at 592nm as y ═ 2.092 multiplied by 10 according to the measured fluorescence intensity8The drug concentration was calculated by x-80.62(pH 6.5), and the drug release rate was obtained as shown in fig. 7(b), and it was found that both the drug release rate and the drug release amount were improved under the 1064nm laser irradiation condition.
Example 3: treatment of colon cancer mice by supramolecular drug-loaded nucleocapsid complex
Establishing a colon cancer cell mouse model: 100 μ L of the extract containing 2X 106A mouse colon cancer cell (CT26) was injected subcutaneously into the leg of male Balb/c mice. When the tumor growth volume reaches about 100 mm3At that time, the experiment was started.
Mice were randomly divided into 5 groups (6 per group): PBS; a supramolecular core-shell complex; a supramolecular drug-loaded core-shell complex; supramolecular core-shell complex +1064nm laser; supramolecular drug-loaded core-shell complex +1064nm laser. On days 1, 3, 5, 7, 9, 11, 13, mice were injected with material via the tail vein and the mice were weighed and tumor volumes recorded. For the mice using the laser group, a 1064nm laser (1.0W/cm) was used 3 hours after the injection2) Irradiating tumor part for 10 min/piece with infrared rayAnd (3) a thermal imager is used for shooting the temperature change of the laser irradiation part (figure 8), the temperature of the tumor part of the mouse is obviously increased under the laser irradiation by the supermolecular core-shell complex, and the temperature of the tumor part is rapidly increased from about 35 ℃ to 54 ℃ within 10 minutes respectively, so that the generated heat is enough to kill cancer cells.
Relative changes in tumor volume in mice were measured and calculated prior to each treatment and body weights of mice were recorded. The tumor growth trend in mice is shown in fig. 9, and it can be seen from fig. 9 that:
first set (PBS): the tumor volume in mice increases rapidly and continuously;
second group (supramolecular core-shell complexes): tumor growth was slightly inhibited in mice of the second group compared to the first group;
third group (supramolecular drug-loaded nucleocapsid complex group): the inhibition effect is more obvious due to the action of the anti-cancer drugs, but the total tumor volume of the mice still shows an increasing trend;
the first, second and third groups of experiments show that the drug-loaded nucleocapsid compound can exert the curative effect in mice, but the tumor is difficult to eradicate only by chemotherapy.
Fourth group (supramolecular core-shell complex +1064nm laser): the mouse tumor is obviously reduced under the photo-thermal treatment, gradually heals and finally disappears;
fifth group (supramolecular drug-loaded core-shell complex +1064nm laser): compared with the fourth group, the tumors of the mice in the fifth group are cured more obviously under the photo-thermal treatment;
the five groups of experiments show that the tumor treatment effect of the chemical-photothermal combination therapy is the best.
Fig. 10 is a graph of the weight change trend of mice in the treatment process, and the weight average of the mice in each group is not obviously reduced, which proves that the material has good biocompatibility with organisms.
On day 14 treatment was terminated, the mice were photographed at the tumor sites, sacrificed, the tumors removed, washed, photographed and weighed to obtain fig. 11 and 12. From fig. 11, the size of the tumor and the corresponding mouse after 14 days of different treatments can be visualized; tumor mass weighing results were consistent with the above conclusions (fig. 12).
In conclusion, the supramolecular drug-loaded core-shell complex provided by the invention is simple in preparation method, good in biocompatibility and strong in photothermal conversion capability, and has a remarkable treatment effect on malignant tumors in chemotherapy-photothermal combined anticancer treatment.
While embodiments of the invention have been described above, it is not limited to the applications set forth in the description and the embodiments, which are fully applicable to various fields of endeavor with which the invention may be practiced, and further modifications may readily be effected therein by those skilled in the art, without departing from the general concept as defined by the claims and their equivalents, which are not limited to the details given herein and the examples shown and described herein.
Claims (8)
1. A method for preparing a supramolecular core-shell complex, comprising:
dissolving the column [5] arene modified by sodium decacarboxylate in water, and adjusting the pH to 5-7 by using a buffer solution to obtain an aqueous solution of the column [5] arene modified by sodium decacarboxylate;
dissolving amphiphilic aniline tetramer into the aqueous solution of the column [5] aromatic hydrocarbon, performing ultrasonic treatment to fully mix the amphiphilic aniline tetramer and the aqueous solution, and adjusting the pH value of the mixed solution to 7-8 by using a buffer solution to obtain a supermolecule core-shell complex aqueous solution; wherein the amphiphilic aniline tetramer has the following molecular structural formula:
2. The method for preparing supramolecular core-shell complexes according to claim 1, wherein the molar ratio of amphiphilic aniline tetramer to sodium decacarboxylate modified column [5] arene is 1: 1.
3. An aqueous solution of supramolecular core-shell complexes produced by the method of claim 1 or 2.
4. A preparation method of a supramolecular drug-loaded core-shell complex is characterized in that a set amount of anticancer drug is added into the supramolecular core-shell complex aqueous solution of claim 3, the anticancer drug is loaded into a hydrophobic core of the supramolecular core-shell complex through mechanical stirring to obtain a supramolecular drug-loaded core-shell complex solution, and the unencapsulated anticancer drug is removed through a dialysis method to obtain the supramolecular drug-loaded core-shell complex solution.
5. The method of preparing the supramolecular drug-loaded core-shell complex of claim 4, wherein the anticancer drug is doxorubicin.
6. The method of preparing the supramolecular drug-loaded core-shell complex of claim 4, wherein the molar ratio of the anticancer drug to the supramolecular core-shell complex is 1: 2.
7. The supramolecular drug-loaded core-shell complex prepared by the preparation method of any one of claims 4 to 6.
8. Use of the supramolecular drug-loaded core-shell complex of claim 7 in the preparation of an anti-tumor drug.
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