CN108478542B - Preparation method and application of hyaluronic acid coated tripterine nano-drug - Google Patents
Preparation method and application of hyaluronic acid coated tripterine nano-drug Download PDFInfo
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Abstract
The invention belongs to the technical field of cancer drugs, and discloses a preparation method and application of a hyaluronic acid coated tripterine nano-drug, wherein the hyaluronic acid coated tripterine nano-drug consists of tripterine and hyaluronic acid; the molar concentration of the tripterine is 10-50 mM/L; the molar concentration of the hyaluronic acid is 10-50 mM/L. The nano-drug provided by the invention can reduce the dosage of tripterine and simultaneously achieve the purpose of high-efficiency anti-tumor treatment. The preparation method of the nano-drug provided by the invention is simple and easy to implement, does not introduce a nano-carrier, is equivalent to a drug loading rate of 100%, and avoids the problem that the drug loading rate is low and a large amount of injection is needed.
Description
Technical Field
The invention belongs to the technical field of cancer drugs, and particularly relates to a preparation method and application of a hyaluronic acid coated tripterine nano-drug.
Background
Currently, the current state of the art commonly used in the industry is such that:cancer is one of the most serious diseases threatening human health, and it involves various genetic variations and cellular abnormalities. The complexity and heterogeneity contribute to the aggressive proliferation of cancer cells, resulting in a generally high incidence and mortality for cancer patients. Unfortunately, because of the poor selectivity of the chemotherapy drugs, the cancer cells are killed and the normal cells of the human body are inevitably damaged, so that the adverse reaction of the drugs occurs. In addition, some chemotherapeutic drugs such as paclitaxel have to use organic solvents because they are difficult to dissolve in water, but the use of organic solvents often causes some immune reactions in the body, which aggravates the pain of the chemotherapeutic process. Currently, the problems of toxic side effects and solubility of chemotherapeutic drugs are generally solved by using a nano drug-loaded delivery system. The nano-carrier assisted drug delivery system establishes a novel cancer treatment means and achieves huge achievement. However, the nanocarrier assisted drug delivery system still has its inevitable disadvantages. E.g. largeMost vectors do not have a direct therapeutic effect, and they can cause additional long-term or short-term toxicity to the organism. In addition, the complex carrier synthesis process and drug loading step limit the wide application of the nano drug loading technology. Tripterygium wilfordii Hook F, Tw HF) is a Celastraceae tripterygium plant, tripterine is one of main components extracted from tripterygium wilfordii, and has multiple pharmacological activities. Tripterine can inhibit tumor tissue angiogenesis, slow down tumor growth, induce tumor cell apoptosis by inhibiting tumor cell protease system, and has tumor inhibiting effect up to 65-93% higher than that of taxol. However, tripterine has poor water solubility, poor oral absorption and systemic toxicity, so that the applicability of the tripterine is limited. Hyaluronic Acid (HA), also known as Hyaluronic acid, is a major component of natural cell matrix and widely exists in the vitreous humor, synovial fluid, and other related tissues of skin and eyes. HA is a white, amorphous solid, readily soluble in water, insoluble in organic solvents, and HAs strong hygroscopicity, and is an excellent natural moisturizing factor. Secondly, HA degrades rapidly and lymphoid tissues will be injected without antigenicity and can exist in any organism without species and tissue differences.
In summary, the problems of the prior art are as follows:nanocarrier-assisted drug delivery systems have no direct therapeutic effect, while carriers can cause additional long-term or short-term toxicity to the organism; in addition, the complex carrier synthesis process and drug loading step limit the wide application of the nano drug loading technology.
The difficulty and significance for solving the technical problems are as follows:the removal of the nano-carrier directly nano-converts the drug, which requires the drug to have the nano-scale characteristic and also maintains the activity of the drug, so that the drug has certain requirements on the drug molecule, requires the drug molecule to have hydrophilic and hydrophobic parts, and can be spontaneously assembled in an aqueous solution to form nano-particles through a reprecipitation method. The tripterine drug molecules selected by the inventor can form nanoscale in aqueous solutionThe particles can increase the stability and targeting property of the particles after hyaluronic acid is added. The hyaluronic acid coated tripterine nano-drug improves the water solubility and blood circulation time of tripterine, enriches more tripterine at tumor parts, overcomes tumor drug resistance, and provides a new treatment idea for tumor treatment.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a preparation method and application of a hyaluronic acid coated tripterine nano-drug.
The invention is realized in such a way, the celastrol nano-drug coated by hyaluronic acid consists of celastrol and hyaluronic acid; tripterine: hyaluronic acid ═ 1: 1-20;
the molar concentration of the tripterine is 10-50 mM/L; the organic solvent is any one of dichloromethane, ethyl propionate, ethanol, methanol, acetone or dimethyl sulfoxide; the molar concentration of the hyaluronic acid is 10-50 mM/L.
Further, the particle size of the hyaluronic acid coated tripterine nano-medicament is 20-500 nm; the hydration particle size of the tripterine nano-drug coated by hyaluronic acid is 100-500 nm.
Further, the particle size of the hyaluronic acid coated tripterine nano-medicament is 50-300 nm.
The invention also aims to provide a preparation method of the hyaluronic acid coated tripterine nano-drug, which comprises the following steps:
dissolving tripterine in an organic solvent to obtain a solution A;
dissolving hyaluronic acid in water to obtain a solution B;
injecting the obtained solution A into deionized water, and stirring to obtain a solution C;
and step four, adding the obtained solution B into the obtained solution C, mixing to obtain a solution D, and stirring to obtain the nano-drug, namely the tripterine nano-drug.
Further, the molar concentration of the tripterine in the solution A is 10-50 mM/L; the organic solvent is any one of dichloromethane, ethyl propionate, ethanol, methanol, acetone or dimethyl sulfoxide; the molar concentration of the hyaluronic acid in the solution B is 10-50 mM/L.
Further, the stirring in the third step is magnetic stirring; the rotating speed of the magnetic stirring is 50-2500 rpm; the temperature of the magnetic stirring is 20-80 ℃.
Further, the molar concentration of the tripterine in the solution C in the third step is 0.1-10 mM/L; the molar concentrations of the tripterine and the hyaluronic acid in the solution D in the fourth step are independently 0.1mM/L, 1mM/L, 3mM/L, 5mM/L, 7mM/L or 10 mM/L.
Further, the volume of the solution B added in the fourth step is 1-20 times of the volume of the solution A in the third step; the stirring in the fourth step is magnetic stirring; the rotating speed of the magnetic stirring is 50-2500 rpm; the magnetic stirring time is 2-48 h; the temperature of magnetic stirring is 20-80 ℃.
The invention also aims to provide a medicine prepared from the hyaluronic acid coated tripterine nano-medicine for treating cancer.
The invention also aims to provide a specific cancer-site-targeting drug prepared from the hyaluronic acid-coated tripterine nano-drug.
In summary, the advantages and positive effects of the invention are:
preparing hydrophobic medicine tripterine into nano-sized medicine coated by hyaluronic acid. The invention directly nanocrystallizes the drug under the condition of no existence of a nano carrier, improves the solubility of the tripterine and simultaneously avoids system toxicity caused by the introduction of the carrier. The nanometer medicine has simple preparation process, and can effectively reduce side effects of chemotherapy on normal tissues and ensure therapeutic effect.
The nano-drug provided by the invention can be well dispersed in an aqueous solution, more drugs can be accumulated at a diseased part, and the aim of targeting is achieved; cell experiments show that compared with single medicine, the nano-medicine provided by the invention can achieve a more efficient tumor killing effect; the nano-drug provided by the invention can reduce the dosage of tripterine and simultaneously achieve the purpose of high-efficiency anti-tumor treatment. The preparation method of the nano-drug provided by the invention is simple and easy to implement, does not introduce a nano-carrier, is equivalent to a drug loading rate of 100%, and avoids the problem that the drug loading rate is low and a large amount of injection is needed.
Drawings
Fig. 1 is a flow chart of a preparation method of a hyaluronic acid coated tripterine nano-drug provided in an embodiment of the present invention.
FIG. 2 is a TEM image of hyaluronic acid coated tripterine nano-drug provided in the embodiment of the present invention.
Fig. 3 is a distribution diagram of hydrated particle size of tripterine nano-drugs coated with hyaluronic acid in example 2 according to an embodiment of the present invention.
FIG. 4 is a graph showing the results of the cell viability of MDA-MB-231 cells tested by the CCK-8 method of the present invention after being treated with different concentrations of the tripterine nano-drug coated with the hyaluronic acid of example 3 for 24 hours.
FIG. 5 is a comparison of the effects provided by embodiments of the present invention;
in the figure: a blank control group has a killing effect result graph on human breast cancer cell MDA-MB-231 cells; b, a result chart of the killing effect of the tripterine group on human breast cancer MDA-MB-231 cells; c is the result chart of the killing effect of the tripterine nano-drug coated with the lithospermic acid on MDA-MB-231 cells provided in example 5.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The hyaluronic acid coated tripterine nano-drug provided by the embodiment of the invention consists of tripterine and hyaluronic acid, wherein the tripterine: hyaluronic acid molar mass ratio of 1: 1-20; the tripterine and the hyaluronic acid interact to form stable nano particles, can be well dispersed in an aqueous solution, and accumulate the medicament at a pathological change part through an EPR effect, so that the targeting characteristic is realized; and cell experiments show that compared with single administration, the nano-drug provided by the invention can achieve more efficient tumor killing effect; the nano-drug provided by the invention can reduce the dosage of tripterine and simultaneously achieve the purpose of high-efficiency anti-tumor treatment. The molar concentration of the tripterine is 10-50 mM/L; the organic solvent is any one of dichloromethane, ethyl propionate, ethanol, methanol, acetone or dimethyl sulfoxide; the molar concentration of the hyaluronic acid is 10-50 mM/L.
The particle size of the nano-drug is 20-500nm, preferably 50-300 nm; the 20-500nm can be 20nm, 50nm, 100nm, 150nm, 300nm, 450nm, 500nm, etc.
The hydrated particle size of the nano-drug is 100-500nm, such as 100nm, 200nm, 300nm, 400nm, 500nm and the like.
In the present invention, the particle size of the nano-drug refers to the particle size of the drug in a powder state after the nano-drug is dried, and the particle size measured under a transmission electron microscope is the particle size of the nano-drug; the hydrated particle size of the nano-drug refers to the particle size of a hydrate formed by dispersing the nano-drug in water, and the particle size measured by dynamic light scattering is the hydrated particle size generally; in the present invention, the average particle diameter is referred to regardless of the particle diameter or hydrated particle diameter.
As shown in fig. 1, the preparation method of the hyaluronic acid coated tripterine nano-drug provided by the embodiment of the invention comprises the following steps:
s101: dissolving tripterine in an organic solvent to obtain a solution A;
s102: dissolving hyaluronic acid in water to obtain a solution B;
s103: injecting the obtained solution A into deionized water, and stirring to obtain a solution C;
s104: adding the obtained solution B into the obtained solution C, mixing to obtain solution D, and stirring to obtain nanometer medicinal preparation, i.e. tripterine nanometer medicinal preparation.
The nano-scale drug is prepared by a precipitation method, and does not need to be combined with a drug carrier, so that the problems of biological system toxicity and immunogenicity caused by a carrier material are solved. The preparation method provided by the invention is simple and feasible, and the yield is high and easy to amplify.
In the present invention, the molar concentration of tripterine in the solution A in step (1) is 10-50mM/L, such as 10mM/L, 15mM/L, 20mM/L, 25mM/L, 30mM/L, 35mM/L, 40mM/L, 45mM/L, 50mM/L, etc.
Preferably, the organic solvent in step (1) is any one of dichloromethane, ethyl propionate, ethanol, methanol, acetone or dimethyl sulfoxide
Preferably, the molar concentration of hyaluronic acid in the solution B in step (2) is 10-50mM/L, such as 10mM/L, 15mM/L, 20mM/L, 25mM/L, 30mM/L, 35mM/L, 40mM/L, 45mM/L, 50mM/L, etc.
Preferably, the stirring in step (3) is magnetic stirring.
Preferably, the rotation speed of the magnetic stirring in step (3) is 50-2500rpm, such as 50rpm, 100rpm, 200rpm, 300rpm, 400rpm, 800rpm, 1200rpm, 1600rpm, 2000rpm, 2500rpm and the like.
Preferably, the temperature of the magnetic stirring in step (3) is 20 ℃ to 80 ℃, such as 20 ℃, 30 ℃, 40 ℃, 50 ℃, 70 ℃, 80 ℃ and the like.
Preferably, the molar concentration of tripterine in the solution C in step (3) is 0.1-10mM/L, e.g., 0.1mM/L, 1mM/L, 3mM/L, 5mM/L, 7mM/L, 10mM/L, etc
Preferably, the molar concentrations of the tripterine and the hyaluronic acid in the solution D in the step (4) are independently 0.1mM/L, 1mM/L, 3mM/L, 5mM/L, 7mM/L, 10mM/L and the like.
Preferably, the volume of solution B added in step (4) is 1-20 times, e.g., 5 times, 10 times, 15 times, 20 times, etc., the volume of solution A added in step (3).
In the invention, the stirring in the step (4) is magnetic stirring.
Preferably, the rotation speed of the magnetic stirring in the step (4) is 50-2500rpm, such as 550rpm, 100rpm, 200rpm, 300rpm, 400rpm, 800rpm, 1200rpm, 1600rpm, 2000rpm, 2500rpm and the like.
Preferably, the magnetic stirring time in step (4) is 2-48h, such as 2h, 5h, 10h, 20h, 30h, 40h, 48h and the like.
Preferably, the temperature of the magnetic stirring in step (4) is 20 ℃ to 80 ℃, such as 20 ℃, 25 ℃, 30 ℃, 40 ℃, 50 ℃, 70 ℃, 75 ℃, 80 ℃ and the like.
In the process of preparing the nano-drug, no toxic organic reagent is introduced or the dosage of the organic reagent which can be introduced can be ignored, so that the possible biological toxicity problem is avoided to a certain extent.
The preparation method provided by the invention forms nanoparticles with uniform particle size from the hydrophobic drug tripterine by reprecipitation, and can achieve the characteristics of improving the bioavailability of the hydrophobic drug, prolonging the blood circulation time and having targeting property.
As a preferred technical scheme, the preparation method comprises the following steps:
(1) dissolving tripterine in an organic solvent to obtain a solution A with the tripterine molar concentration of 10-50 mM/L;
(2) dissolving hyaluronic acid in water to obtain solution B with hyaluronic acid concentration of 10-50 mM/L;
(3) injecting the solution A obtained in the step (1) into deionized water, and carrying out magnetic stirring at the rotating speed of 50-2500rpm at the temperature of 20-80 ℃ to obtain a solution C with the molar concentration of the tripterine of 0.1-10 mM/L;
(4) adding the solution B obtained in the step (2) into the solution C obtained in the step (3) to obtain a solution D by mixing, wherein the volume of the solution B added in the step (4) is 1-20 times of the volume of the solution A in the step (3), the molar concentration of the tripterine and the hyaluronic acid in the solution D is independently 0.1-10mM/L, and performing magnetic stirring at the rotation speed of 50-2500rpm at the temperature of 20-80 ℃ for 2-48h to obtain the nano-drug, namely the tripterine nano-drug.
The invention provides application of the nano-drug in preparation of a drug for treating cancer.
The nano-drug provided by the invention has the advantages that the particle size is in a nano level, the nano-drug has a good solid tumor retention (EPR) effect, can specifically target cancer parts, and is applied to the preparation of drugs for treating cancers.
The application of the principles of the present invention will now be described in further detail with reference to specific embodiments.
Example 1
The nano-drug provided by the embodiment comprises tripterine, and the particle size of the nano-drug is 90nm, and the hydrated particle size is 120 nm.
The preparation method comprises the following steps:
(1) dissolving 5mg of tripterine in 1.25mL of dimethyl sulfoxide to obtain a solution A with the tripterine molar concentration of 10 mM/L;
(2) dissolving 7.8mg of hyaluronic acid in 1mL of water to obtain a solution B with the molar concentration of the hyaluronic acid being 10 mM/L;
(3) injecting 100 mu L of the solution A obtained in the step (1) into 800 mu L of tertiary water, injecting into deionized water, and carrying out magnetic stirring at the rotating speed of 100rpm at the temperature of 20 ℃ to obtain a solution C;
(4) and (3) injecting 100 mu L of the solution B obtained in the step (2) into the solution C obtained in the step (3) for mixing to obtain a solution D, and magnetically stirring at the rotating speed of 100rpm at 20 ℃ for 24 hours to obtain the nano-drug.
As shown in fig. 2, it can be seen from fig. 1 that the nano-drug provided by this embodiment has small particle size, is at nano level, and has uniform particle size.
Example 2
The nano-drug provided by the embodiment comprises tripterine, and the particle size of the nano-drug is 80nm, and the hydrated particle size is 114.3 nm.
The preparation method comprises the following steps:
(1) dissolving 50mg tripterine in 1.25mL methanol to obtain solution A;
(2) dissolving 78mg of hyaluronic acid in 1mL of water to obtain a solution B;
(3) injecting 10 mu L of the solution A obtained in the step (1) into 890 mu L of tertiary water, injecting into deionized water, and carrying out magnetic stirring at the rotating speed of 2000rpm at 25 ℃ to obtain a solution C;
(4) and (3) injecting 100 mu L of the solution B obtained in the step (2) into the solution C obtained in the step (3) for mixing to obtain a solution D, and magnetically stirring at the rotating speed of 2000rpm at 25 ℃ for 12h to obtain the nano-drug.
The dynamic light scattering test (DLS) is performed on the nano-drug provided in this example, and the measured result is the hydrated particle size of the nano-drug, and the result is shown in fig. 3, which shows that the particle size of the nano-particle of the present invention is 114.3nm, and the peak value in the figure is very prominent, which indicates that the particle size distribution of the nano-particle of the present invention is uniform.
Example 3
The nano-drug provided by the embodiment comprises tripterine, and the particle size of the nano-drug is 80nm, and the hydrated particle size is 150 nm.
The preparation method comprises the following steps:
(1) dissolving 22.5mg tripterine in 12.5mL dichloromethane to obtain solution A;
(2) dissolving 7.8mg of hyaluronic acid in 1mL of water to obtain a solution B;
(3) injecting 32 mu L of the solution A obtained in the step (1) into 808 mu L of tertiary water, injecting into deionized water, and carrying out magnetic stirring at the rotating speed of 2500rpm at 50 ℃ to obtain a solution C;
(4) and (3) injecting 200 mu L of the solution B obtained in the step (2) into the solution C obtained in the step (3) for mixing to obtain a solution D, and magnetically stirring at the rotating speed of 2500rpm at 50 ℃ for 20 hours to obtain the nano-drug.
Example 4
The nano-drug provided by the embodiment comprises tripterine, and the particle size of the nano-drug is 150nm, and the hydrated particle size is 225 nm.
The preparation method comprises the following steps:
(1) dissolving 5mg tripterine in 2.5mL chloroform to obtain solution A;
(2) dissolving 0.78mg of hyaluronic acid in 1mL of water to obtain a solution B;
(3) injecting 50 mu L of the solution A obtained in the step (1) into 630 mu L of tertiary water, injecting into deionized water, and carrying out magnetic stirring at the rotating speed of 1000rpm at 60 ℃ to obtain a solution C;
(4) and (3) injecting 320 mu L of the solution B obtained in the step (2) into the solution C obtained in the step (3) for mixing to obtain a solution D, and magnetically stirring at the rotating speed of 1000rpm at 60 ℃ for 12h to obtain the nano-drug.
Example 5
The nano-drug provided by the embodiment comprises tripterine, and the particle size of the nano-drug is 250nm, and the hydrated particle size is 400 nm.
(1) Dissolving 10mg of tripterine in 1mL of dimethyl sulfoxide to obtain a solution A;
(2) dissolving 7.8mg of hyaluronic acid in 2mL of dehydrated water to obtain a solution B;
(3) injecting 10 mu L of the solution A obtained in the step (1) into 800 mu L of tertiary water, injecting into deionized water, and carrying out magnetic stirring at the rotating speed of 1500rpm at 25 ℃ to obtain a solution C;
(4) and (3) injecting 100 mu L of the solution B obtained in the step (2) into the solution C obtained in the step (3) for mixing to obtain a solution D, and magnetically stirring at the rotating speed of 1500rpm at 25 ℃ for 6h to obtain the nano-drug.
The effect of the present invention will be described in detail with reference to the experiments.
Experiment 1
In this experimental example, the effect of the nano-drug provided in example 3 on the viability of the MDA-MB-231 cells was examined by performing CCK-8 colorimetric experiments on the MDA-MB-231 cells, as follows:
(1) cell culture
Human breast cancer cell MDA-MB-231 is cultured in DMEM or 1640 liquid culture medium containing 10% fetal bovine serum and cultured in an incubator at 37 ℃ and 5% carbon dioxide.
(2) Cell viability assay
Cells were seeded in 96-well plates at 8000 cells/well density, and 24h after adherence, the cells were divided into 3 groups, which were blank control group, tripterine group, and nano-drug group provided in example 5, respectively. The blank control group was not treated, and the amount of tripterine added to the tripterine group was 0. mu.M, 10. mu.M, 15. mu.M, 20. mu.M, and 25. mu.M, respectively. The nano-drug groups provided in example 5 were added at 0. mu.M, 10. mu.M, 15. mu.M, 20. mu.M, 25. mu.M. After the drug treatment is carried out for 24 hours, the culture medium is removed; mu.L of cell culture solution containing 10 percent (volume ratio) of CCK-8 is added into each well, after incubation for 2h in an incubator, the absorbance value at 450nm is measured on a microplate reader, and 600nm is used as a reference wavelength. After the absorbance value of the blank solution is subtracted from the absorbance value of each group, the corresponding value of each hole is divided by the absorbance value of the control group to be used as the cell activity. Each set was provided with 6 parallel holes.
The cell viability measurement result is shown in fig. 4, compared with the control group, the nano-drug prepared in example 5 significantly inhibits the viability of MDA-MB-231 cells, and compared with the single tripterine-treated group, the nano-drug provided by the invention has the highest inhibition rate on MDA-MB-231 cells, which indicates that the nano-drug synthesized by the method can reach the same or even better tumor inhibition effect with lower drug concentration.
Experiment 2
In this experimental example, the nano-drug provided by the present invention was tested by killing the celastrol group and the nano-drug group provided in example 5 against MDA-MB-231 cells, and the method thereof was as follows:
(1) cell culture
Human breast cancer cell MDA-MB-231 is cultured in DMEM or 1640 liquid culture medium containing 10% fetal bovine serum and cultured in an incubator at 37 ℃ and 5% carbon dioxide.
(2) Observation of cell Activity
Inoculating the cells cultured in the step 1 into a 6-well plate, adding 2mL of DMEM or 1640 liquid culture medium (containing 10% fetal bovine serum) into each well of 30 ten thousand of cells, placing the cells in a 5% carbon dioxide incubator at 37 ℃ for 24h, and dividing the cells into 3 groups, namely a blank control group, a tripterine group and the nano-drug group provided in the example 5. Then adding celastrol 20 μ M into DMEM or 1640 culture medium containing 10% fetal calf serum, adding the drugs with consistent concentration into each group, adding into 6-well plate, culturing at 37 deg.C in 5% carbon dioxide incubator for 24 hr, and leaving blank control group without any treatment. The medium was removed, the cells were trypsinized, the supernatant was centrifuged at 800g, the cells were resuspended in PBS buffer and the wash repeated three times. The proportion of cell death is analyzed by the annexin V-PI kit detection.
The results are shown in fig. 5A to 5C, the nano-drug of the present invention can cause apoptosis and necrosis, and compared with single tripterine treatment, the nano-drug of the present invention has the highest apoptosis rate on MDA-MB-231 cells, which indicates that the nano-drug synthesized by the method of the present invention can achieve the same or even better tumor inhibition effect with lower drug concentration.
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, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included within the scope of the present invention.
Claims (9)
1. A hyaluronic acid coated tripterine nano-drug is characterized in that the hyaluronic acid coated tripterine nano-drug consists of tripterine and hyaluronic acid; the molar mass ratio of the tripterine to the hyaluronic acid is 1: 1 to 20;
the particle size of the hyaluronic acid coated tripterine nano-drug is 20-500 nm; the hydration particle size of the tripterine nano-drug coated by hyaluronic acid is 100-500 nm.
2. The hyaluronic acid-coated tripterine nano-drug according to claim 1, wherein the particle size of the hyaluronic acid-coated tripterine nano-drug is 50-300 nm.
3. The method for preparing the hyaluronic acid-coated tripterine nano-drug according to claim 1, wherein the method for preparing the hyaluronic acid-coated tripterine nano-drug comprises:
dissolving tripterine in an organic solvent to obtain a solution A;
dissolving hyaluronic acid in water to obtain a solution B;
injecting the obtained solution A into deionized water, and stirring to obtain a solution C;
and step four, adding the obtained solution B into the obtained solution C, mixing to obtain a solution D, and stirring to obtain the nano-drug, namely the tripterine nano-drug.
4. The method of claim 3, wherein the molar concentration of celastrol in solution A is 10-50 mmol/L; the organic solvent is any one of dichloromethane, ethyl propionate, ethanol, methanol, acetone or dimethyl sulfoxide; the molar concentration of the hyaluronic acid in the solution B is 10-50 mmol/L.
5. The method for preparing a hyaluronic acid coated tripterine nano-drug according to claim 3, wherein the stirring in step three is magnetic stirring; the rotating speed of the magnetic stirring is 50-2500 rpm; the temperature of the magnetic stirring is 20-80 ℃.
6. The method for preparing a hyaluronic acid coated tripterine nano-drug according to claim 3, wherein the molar concentration of tripterine in the solution C in the third step is 0.1-10 mmol/L; the molar concentration of the tripterine in the solution D in the step four is independently selected from 0.1mmol/L, 1mmol/L, 3mmol/L, 5mmol/L and 7mmol/L, and the molar concentration of the hyaluronic acid is independently selected from 0.1mmol/L, 1mmol/L, 3mmol/L, 5mmol/L, 7mmol/L or 10 mmol/L.
7. The method for preparing a hyaluronic acid-coated tripterine nano-drug according to claim 3, wherein the volume of the solution B added in step four is 1-20 times of the volume of the solution A in step three; the stirring in the fourth step is magnetic stirring; the rotating speed of the magnetic stirring is 50-2500 rpm; the magnetic stirring time is 2-48 h; the temperature of magnetic stirring is 20-80 ℃.
8. A medicament for treating cancer, which is prepared from the hyaluronic acid coated tripterine nano-medicament of any one of claims 1-2.
9. A specific cancer-site-targeting drug prepared from the hyaluronic acid-coated tripterine nano-drug according to any one of claims 1-2.
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