Copper ion carrier material with photothermal effect, preparation method and anti-cancer drug formed by copper ion carrier material

Abstract

The invention discloses a copper ion carrier material with a photothermal effect, a preparation method and an anti-cancer drug formed by the copper ion carrier material, and belongs to the technical field of nano drug loading technologies, and the structural formula of the copper ion carrier material is as follows: # imgabs0 #. The preparation method comprises the following steps: S1, mixing butanedione and concentrated hydrochloric acid in water, stirring and reacting, adding 4-methyl thiosemicarbazide, continuously stirring and reacting, and performing post-treatment to obtain a compound (4); then dissolving the compound (3) and 4, 4-dimethyl thiourea in a DMSO solvent, dropwise adding glacial acetic acid for reaction, and performing post-treatment to obtain a compound (6); dissolving the compound (6) and 6-aminocaproic acid in an acetonitrile solvent, reacting, and performing post-treatment to obtain a compound (8); and dissolving the compound (8) and beta-cyclodextrin in a DMSO solvent, mixing, adding an activating agent and a condensing agent, reacting, and performing post-treatment to obtain the copper ion carrier material with the photothermal effect. The problems that a copper ion carrier is poor in water solubility, low in photothermal conversion efficiency and low in near-infrared light energy, ultraviolet light is not prone to penetrating into tissues, and tissue damage can be caused are solved.

Description

Technical Field

[0001] The invention relates to the technical field of nano drug delivery, and in particular to a copper ion carrier material with photothermal effect, a preparation method thereof, and an anticancer drug composed thereof. Background Art

[0002] Copper is a kind of trace element essential to human body, and is also a key cofactor in biological redox reaction. It is widely involved in the biosynthesis process in human body, and copper is also an important component of the biological function of cell signal transduction. Copper can promote the death of tumor cells through different mechanisms, so it has attracted wide attention in the field of tumor treatment. For example, the newly discovered copper death is mainly cell death induced by copper-targeted lipoylated tricarboxylic acid cycle proteins (Tsvetkov P., Coy S., Petrova B., et.al. Copper induces cell death by targeting lipoylated TCAcycle proteins. Science, 2022, 375, 1254-1261.). Copper can also catalyze the formation of active hydroxyl radicals through oxidative free radical reaction, resulting in an increase in the concentration of reactive oxygen species (ROS) in tumor cells, thereby killing tumor cells. In addition, some copper complexes can also cause tumor cell death by autophagy-dependent apoptosis. Copper chelates and copper ion carriers are two copper coordination compounds for the treatment of cancer (Xie W., Guo Z., Zhao L., Wei Y. The copper age incancer treatment: From copper metabolism to cuproptosis. Progress in Materials Science, 2023, 138, 101145.). Copper chelates and copper ion carriers can regulate copper ion homeostasis in two ways, such as copper chelators binding to copper ions and reducing copper ions, thereby inhibiting the proliferation and metastasis of tumor cells, or using copper ion carriers to transport copper ions into cells, increasing intracellular Cu 2+ levels, produce reactive oxygen species, induce tumor cell death, etc.

[0003] In addition, copper chalcogenide is a p-type semiconductor with strong intrinsic near-infrared absorption, which is a promising choice for photothermal ablation of cancer cells (Chenglin Y, Qiwei T, Shipping Y, et al. Recent advances intherational design of copper chalcogenide to enhance the photothermal conversion efficiency for the photo thermal ablation of cancer cells. Science, 2017, 7, 37887-37897.). Photothermal ablation therapy is increasingly attracting attention due to its minimally invasive nature, especially in the near-infrared (NIR700-1100nm) region, where laser-induced photothermal ablation therapy gradually occupies an important position in the field of nanotechnology therapy due to the low scattering and small absorption of near-infrared light to tissues and blood and the ability to reach several centimeters inside biological tissues. However, the copper ion carriers in the prior art have poor water solubility, low photothermal conversion efficiency when applying photothermal therapy, low near-infrared light energy, and defects and deficiencies such as poor penetration of ultraviolet light into tissues and tissue damage. Summary of the invention

[0004] In order to solve the above problems, the present invention provides a copper ion carrier material with photothermal effect and a preparation method, and an anticancer drug composed of the copper ion carrier material, which overcomes the problem of poor water solubility of existing copper ion carriers and significantly improves the photothermal conversion efficiency when performing photothermal therapy. It can effectively utilize near-infrared light, such as low energy and deep tissue penetration, while avoiding the risk of tissue damage that may be caused by the use of ultraviolet light.

[0005] The present invention provides a copper ion carrier material with photothermal effect, and its structural formula is as follows:

[0006]

[0007] The present invention provides a method for preparing a copper ion carrier material with a photothermal effect, comprising the following steps:

[0008] S1: Mix diacetyl and concentrated hydrochloric acid in water, stir to react, add 4-methylthiosemicarbazide and continue to stir to react at 0°C, and post-treat to obtain compound C. 6 H 11 N 3 OS;

[0009]

[0010] S2: Compound C obtained in step S16 H 11 N 3 OS and 4,4-dimethylthiourea were dissolved in DMSO solvent, and glacial acetic acid was added for reaction. After post-treatment, compound C was obtained. 9 H 18 N 6 S 2 ;

[0011]

[0012] S3: Compound C obtained in step S2 9 H 18 N 6 S 2 , 6-aminocaproic acid is dissolved in acetonitrile solvent for reaction, and then post-processed to obtain compound

[0013] S4: dissolving the compound obtained in step S3 and β-cyclodextrin in DMSO solvent, adding an activator and a condensing agent after mixing, reacting, and performing post-treatment to obtain a copper ion carrier material with a photothermal effect.

[0014] Preferably, in step S1, the post-treatment method is: after the reaction, the yellowish solid is obtained by vacuum filtration, the solid is washed three times with distilled water, and then dissolved in 50-100 mL of ethanol, and the solid is vacuum filtered again to obtain a filtrate, the solvent is evaporated from the filtrate, and then vacuum dried to obtain compound C 6 H 11 N 3 OS.

[0015] Preferably, in step S2, the post-treatment method is: add 50-80 mL of distilled water to the obtained reaction solution, place it in an ice water bath for 20-40 min, filter it under reduced pressure to obtain a yellow solid, then wash it with distilled water, ethanol, and ether in turn for several times, add 100 mL of ethanol to dissolve the washed yellow solid again, filter it under reduced pressure to obtain a light yellow solid, and then vacuum dry it to obtain compound C 9 H 18 N 6 S 2 .

[0016] Preferably, in step S3, the post-treatment method is: adding 1% hydrochloric acid solution to precipitate a white solid, filtering under reduced pressure to obtain a filter cake, washing it with acetonitrile and ether in small amounts for multiple times, and then vacuum drying to obtain a compound

[0017] Preferably, in step S4, the post-treatment method is: vacuum filtration, adding the filtrate dropwise into acetone to precipitate, collecting the precipitate by centrifugation, dissolving it in DMSO solution, and then gradually adding the mixed solution dropwise into acetone to precipitate a white flocculent precipitate, repeating three times, removing impurities, adding distilled water to dissolve and dialyze, and freeze-drying.

[0018] Preferably, in step S1, the molar ratio of the 4-methylthiosemicarbazide to diacetyl is 1.0:1.0-1.5; in step S2, the compound C 6 H 11 N 3 The molar ratio of OS and 4,4-dimethylthiourea is 1.0 mol:1.0-1.5 mol:; in step S3, the compound C 9 H 18 N 6 S 2 , 6-aminocaproic acid in a molar ratio of 1.0 mol:1.5-2.0 mol; in step S4,

[0019] Compound The molar ratio of β-cyclodextrin, activator and condensing agent is 1.0:(2.0-3.0)mol:(2.0-5.0)mol:(2.0-5.0)mol.

[0020] Preferably, in step S1, after diacetyl and concentrated hydrochloric acid are mixed in water, the stirring reaction temperature is below 0°C and the stirring reaction time is 20-190 min. After adding 4-methylthiosemicarbazide, the stirring reaction temperature is below 0°C and the stirring reaction time is 20-80 min. In step S2, the amount of glacial acetic acid added is 4-11 drops, and the reaction is carried out at room temperature for 3-50 h. In step S3, the reaction is carried out under nitrogen protection, the reaction temperature is 60-90°C, and the reaction time is 24-48 h. In step S4, the reaction is carried out at 20-90°C and the reaction time is 4-48 h.

[0021] Preferably, in step S1, the volume amount of concentrated hydrochloric acid is based on the compound The volume is 200mL / L; in step S3, the activator is one or more of DCC and EDC; the condensing agent is one or more of DMAP, HOBT, and DIEA; in step S4, the molecular weight of the β-cyclodextrin is calculated as a single sugar molecule 162, and the volume amount of DMSO is 30-50mL / g based on the mass of β-cyclodextrin.

[0022] The present invention provides an anticancer drug, comprising Cu 2+And the copper ion carrier material or the copper ion carrier material with photothermal effect prepared according to the preparation method of the copper ion carrier material with photothermal effect, Cu 2+ The nanoparticles are formed by combining with copper ion carrier materials through chelation. 2+ The targeted effect of Cu 2+ on the mitochondria of cells is then used to deliver near-infrared light, generating a temperature that can kill tumors. 2+ Increase intracellular Cu 2+ level, produce reactive oxygen species, induce tumor cell death and thus treat the disease.

[0023] Therefore, the present invention adopts the above-mentioned copper ion carrier material with photothermal effect and preparation method, and the anticancer drug composed of the copper ion carrier material, and improves its solubility in water by introducing a polymer with good biocompatibility; introduces a small molecule compound that can chelate copper ions, and directly targets the mitochondria after chelating a large amount of copper ions to increase the intracellular Cu2+ level; and also increases the intracellular Cu2+ level, generates reactive oxygen, and induces copper death of tumor cells. Near-infrared light / infrared light with high tissue permeability and little in vitro damage can also be used to irradiate the tumor site to produce a temperature that reaches the temperature that kills tumor cells, further improving the effect of cancer treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is the SEM image of nanoparticles formed by copper ion carrier material chelating copper ions.

[0025] Figure 2 The photothermal curves of nanoparticles formed by copper ion carrier materials chelating copper ions under different near-infrared light irradiation;

[0026] Figure 3 The photothermal performance diagram of compound (1) and its copper ion chelate (near infrared light, 808 nm). DETAILED DESCRIPTION

[0027] The present invention provides a copper ion carrier material with photothermal effect, and its structural formula is as follows:

[0028]

[0029] The present invention provides a method for preparing a copper ion carrier material with a photothermal effect, comprising the following steps:

[0030] S1: Mix diacetyl and concentrated hydrochloric acid in water, stir to react, add 4-methylthiosemicarbazide and continue stirring to react at 0°C, and post-treat to obtain compound (4) C 6 H 11 N 3OS; the post-treatment method is: after the reaction, the yellowish solid is obtained by vacuum filtration, washed three times with distilled water, dissolved in 50-100 mL of ethanol, and vacuum filtered again to obtain a filtrate, the filtrate is evaporated to remove the solvent and then vacuum dried to obtain compound (4) C 6 H 11 N 3 OS, the molar ratio of the 4-methylthiosemicarbazide to diacetyl is 1.0:1.0-1.5; after diacetyl and concentrated hydrochloric acid are mixed in water, the stirring reaction temperature is below 0°C, and the stirring reaction time is 20-190 min; after the 4-methylthiosemicarbazide is added, the stirring reaction temperature is below 0°C, and the stirring reaction time is 20-80 min; the volume amount of concentrated hydrochloric acid is 200 mL / L based on the volume of compound (8);

[0031]

[0032] S2 Compound (4) obtained in step S1 6 H 11 N 3 OS and 4,4-dimethylthiourea were dissolved in DMSO solvent, and glacial acetic acid was added for reaction. After post-treatment, compound (6) C was obtained. 9 H 18 N 6 S 2 The post-treatment method is as follows: 50-80 mL of distilled water is added to the obtained reaction solution, and the mixture is placed in an ice-water bath for 20-40 min. After vacuum filtration, a yellow solid is obtained. The mixture is then washed several times in turn with distilled water, ethanol, and ether. The washed yellow solid is added with 100 mL of ethanol and dissolved again. After vacuum filtration, a light yellow solid is obtained, which is then vacuum dried to obtain compound (6) C. 9 H 18 N 6 S 2 ; The compound (4) C 6 H 11 N 3 The molar ratio of OS and 4,4-dimethylthiourea is 1.0 mol:1.0-1.5 mol; the amount of glacial acetic acid added is 4-11 drops, and the reaction is carried out at room temperature for 3-50 hours;

[0033]

[0034] S3 Compound (6) obtained in step S2 9 H 18 N 6 S 2, 6-aminocaproic acid is dissolved in acetonitrile solvent for reaction, and then post-processed to obtain compound (8), wherein the post-processing method is as follows: adding 1% hydrochloric acid solution to precipitate a white solid, filtering under reduced pressure to obtain a filter cake, washing it with acetonitrile and ether in small amounts for multiple times, and then vacuum drying to obtain compound (8); the compound (6) C 9 H 18 N 6 S 2 The molar ratio of the substance of 6-aminocaproic acid is 1.0 mol:1.5-2.0 mol; the activator is one or more of DCC and EDC; the condensing agent is one or more of DMAP, HOBT and DIEA; the reaction is carried out under nitrogen protection, the reaction temperature is 60-90°C, and the reaction time is 24-48h.

[0035]

[0036] S4: dissolving the compound (8) and β-cyclodextrin obtained in step S3 in DMSO solvent, adding an activator and a condensing agent after mixing, and performing post-treatment after reaction to obtain a copper ion carrier material with photothermal effect. The post-treatment method is as follows: vacuum filtration, adding the filtrate dropwise into acetone to precipitate, collecting the precipitate by centrifugation, dissolving it in DMSO solution, and then gradually adding the mixed solution dropwise into acetone to precipitate a white flocculent precipitate, repeating the process three times, removing impurities, adding distilled water to dissolve and dialyze, and freeze-drying to obtain a copper ion carrier material with photothermal effect; the molar ratio of compound (8), β-cyclodextrin, activator, and condensing agent is 1.0:(2.0-3.0):(2.0-5.0):(2.0-5.0), the molecular weight of the β-cyclodextrin is calculated as a single sugar molecule 162, the volume amount of DMSO is 30-50 mL / g based on the mass of β-cyclodextrin, the reaction is carried out at 20-90° C., and the reaction time is 4-48 h.

[0037] The synthetic route is as follows:

[0038]

[0039] Example 1

[0040] In a 100 mL round-bottom flask, diacetyl (2.42 mL, 27.6 mmol), distilled water (30 mL), and concentrated hydrochloric acid (0.5 mL) were added. The mixture was stirred at 0°C for 1.5 h, followed by the addition of 4-methylthiosemicarbazide (2.65 g, 25.0 mmol). The mixture was stirred at 0°C for 40 min, and then filtered under reduced pressure to obtain a slightly yellow solid. The solid was washed three times with distilled water, dissolved in 50-100 mL of ethanol, and filtered under reduced pressure again to obtain a filtrate. The solvent was evaporated from the filtrate and dried under vacuum to obtain compound (4) with a yield of 76.3%.

[0041] Example 2

[0042] In a 100 mL round-bottom flask, diacetyl (2.19 mL, 25.0 mmol), distilled water (30 mL), and concentrated hydrochloric acid (0.5 mL) were added. The mixture was stirred at 0°C for 1.5 h, followed by the addition of 4-methylthiosemicarbazide (2.65 g, 25.0 mmol). The mixture was stirred at 0°C for 40 min, and then filtered under reduced pressure to obtain a slightly yellow solid. The solid was washed three times with distilled water, dissolved in 50-100 mL of ethanol, and filtered under reduced pressure again to obtain a filtrate. The solvent was evaporated from the filtrate, and then dried under vacuum to obtain compound (4) with a yield of 72.8%.

[0043] Example 3

[0044] In a 100 mL round-bottom flask, add compound 4 (920 mg, 5 mmoL) obtained in Example 1, 4,4-dimethylthiourea (760 mg, 6 mmoL), DMSO (5 mL), and then add 10 drops of glacial acetic acid and continue stirring at room temperature for 48 h. After the reaction is completed, add 50 mL of distilled water to the reaction solution, place it in an ice-water bath for 30 min, and filter it under reduced pressure to obtain a yellow solid. Then wash it with distilled water, ethanol, and ether three times in turn. Add 100 mL of ethanol to dissolve the washed solid again, filter it under reduced pressure to obtain a slightly yellow solid, and then vacuum dry it to obtain compound (6), with a yield of 66.7%.

[0045] Example 4

[0046] In a 100 mL round-bottom flask, add compound 4 (920 mg, 5 mmoL) obtained in Example 1, 4,4-dimethylthiourea (596 mg, 5 mmoL), DMSO (5 mL), and then add 10 drops of glacial acetic acid and continue stirring at room temperature for 48 h. After the reaction is completed, add 50 mL of distilled water to the reaction solution, place it in an ice water bath for 30 min, and filter it under reduced pressure to obtain a yellow solid. Then wash it with distilled water, ethanol, and ether three times in turn. Add 100 mL of ethanol to dissolve the washed solid again, filter it under reduced pressure to obtain a slightly yellow solid, and then vacuum dry it to obtain compound (6), with a yield of 62.5%.

[0047] Example 5

[0048] In a 100 mL three-necked flask, compound 6 (280 mg, 1 mmoL) obtained in Example 3, 6-aminocaproic acid (210 mg, 1.6 mmoL) and acetonitrile (30 ml) were added and reacted at 80°C for 34 h under nitrogen protection. After the reaction, 1% hydrochloric acid solution was added to the reaction solution to precipitate a white solid, which was filtered under reduced pressure to obtain a filter cake, which was washed with acetonitrile and ether in small amounts for multiple times and then dried in vacuum to obtain compound (8) with a yield of 70.3%.

[0049] Example 6

[0050] In a 100 mL three-necked flask, compound 6 (420 mg, 1.5 mmol) obtained in Example 3, 6-aminocaproic acid (315 mg, 2.4 mmol) and acetonitrile (30 ml) were added and reacted at 80°C for 48 h under nitrogen protection. After the reaction, 1% hydrochloric acid solution was added to the reaction solution to precipitate a white solid, which was filtered under reduced pressure to obtain a filter cake, which was washed with acetonitrile and ether in small amounts for multiple times and then dried in vacuum to obtain compound (8) with a yield of 76.7%.

[0051] Example 7

[0052] In a 100 mL round-bottom flask, add compound 8 (89 mg, 0.25 mmol) obtained in Example 6, β-cyclodextrin (80 mg, 0.5 mmol), EDC (95 mg, 0.5 mmol), HoBt (67 mg, 0.5 mmol), DIEA (0.5 mmol), and DMSO (5 mL) and stir at room temperature for 24 h. The reaction solution was filtered under reduced pressure, and the filtrate was added dropwise to acetone to precipitate. The precipitate was collected by centrifugation at 12000 rpm for 10 min, dissolved in a small amount of DMSO solution, and then gradually added dropwise to acetone to precipitate a white flocculent precipitate. Repeat three times, remove impurities, add a small amount of distilled water to dissolve and dialyze for 3 days, and freeze-dry for 24 h to obtain compound (1) with a yield of 68.4%.

[0053] Example 8

[0054] In a 100 mL round-bottom flask, add compound 8 (89 mg, 0.25 mmol) obtained in Example 6, β-cyclodextrin (80 mg, 0.5 mmol), EDC (95 mg, 0.5 mmol), HoBt (67 mg, 0.5 mmol), DIEA (0.5 mmol), and DMSO (5 mL) and stir at room temperature for 36 h. The reaction solution was filtered under reduced pressure, and the filtrate was added dropwise to acetone to precipitate. The precipitate was collected by centrifugation at 12000 rpm for 10 min, dissolved in a small amount of DMSO solution, and then gradually added dropwise to acetone to precipitate a white flocculent precipitate. Repeat three times, remove impurities, add a small amount of distilled water to dissolve and dialyze for 3 days, and freeze-dry for 36 h to obtain compound (1) with a yield of 71.2%.

[0055] Example 8

[0056] In a 100 mL round-bottom flask, add compound 8 (89 mg, 0.25 mmoL) obtained in Example 6, β-cyclodextrin (80 mg, 0.5 mmoL), EDC (95 mg, 0.5 mmoL), HoBt (67 mg, 0.5 mmoL), DIEA (0.5 mmoL), and DMSO (5 mL) and stir at room temperature for 48 h. The reaction solution was filtered under reduced pressure, and the filtrate was added dropwise to acetone to precipitate. The precipitate was collected by centrifugation at 12000 rpm for 10 min, dissolved in a small amount of DMSO solution, and then gradually added dropwise to acetone to precipitate a white flocculent precipitate. Repeat three times, remove impurities, add a small amount of distilled water to dissolve and dialyze for 3 days, and freeze-dry for 36 h to obtain compound (1) with a yield of 73.9%.

[0057] Example 9

[0058] In a 100 mL round-bottom flask, add compound 8 (89 mg, 0.25 mmoL) obtained in Example 6, β-cyclodextrin (80 mg, 0.5 mmoL), EDC (240 mg, 1.25 mmoL), HoBt (169 mg, 1.25 mmoL), DIEA (162 mg, 1.25 mmoL), and DMSO (5 mL) and stir at room temperature for 36 h. The reaction solution was filtered under reduced pressure, and the filtrate was added dropwise to acetone to precipitate. The precipitate was collected by centrifugation at 12000 rpm for 10 min, dissolved in a small amount of DMSO solution, and then gradually added dropwise to acetone to precipitate a white flocculent precipitate. Repeat three times, remove impurities, add a small amount of distilled water to dissolve and dialyze for 3 days, and freeze-dry for 36 h to obtain compound (1) with a yield of 71.8%.

[0059] Example 10

[0060] In a 100 mL round-bottom flask, compound 8 (89 mg, 0.25 mmoL) obtained in Example 6, β-cyclodextrin (80 mg, 0.5 mmoL), EDC (95 mg, 1.25 mmoL), HoBt (67 mg, 1.25 mmoL), DIEA (162 mg, 1.25 mmoL), and DMSO (5 mL) were added and stirred at room temperature for 48 h. The reaction solution was filtered under reduced pressure, and the filtrate was added dropwise to acetone to precipitate. The precipitate was collected by centrifugation at 12000 rpm for 10 min, dissolved in a small amount of DMSO solution, and then gradually added dropwise to acetone to precipitate a white flocculent precipitate. This was repeated three times. After removing impurities, a small amount of distilled water was added to dissolve and dialyze for 3 days, and freeze-dried for 36 h to obtain compound (1) with a yield of 75.3%.

[0061] Embodiment 11

[0062] 139 mg of compound (1) prepared in Example 10 was weighed and dissolved in 4 mL of DMSO to prepare a solution. Then, CuCl2 37 mg was dissolved in 1 mL DMSO solution to prepare a solution. 2 The solution was dripped into the solution of compound (1) drop by drop, and stirred for 8 hours after dripping. After the reaction was completed, the reaction solution was dripped into 300 mL of acetone drop by drop, and stirred for 2 hours. Finally, the nanoparticles formed after chelating copper were collected by centrifugation at 12000 rpm for 20 minutes. The nanoparticles were redispersed in 1 mL of distilled water to prepare a 1 mg / mL solution, and then dripped onto the smooth surface of the silicon wafer. The silicon wafer had been cut into appropriate sizes in advance and soaked in an appropriate amount of anhydrous ethanol for 1 hour for use. After natural air drying, the morphology can be observed using a scanning electron microscope. Figure 1 shown.

[0063] Example 12

[0064] 5 mg of the compound (1) prepared in Example 11 was weighed and placed in the middle of a glass culture dish, and then irradiated with 808 nm laser at 0.9 W, 1.0 W, 1.1 W, and 1.2 W, respectively, to obtain the photothermal curves of the nanoparticles formed after chelating copper under near-infrared light irradiation of different powers as shown in FIG. Figure 2 As shown in the figure. Under 0.9W, 808nm laser irradiation, the nanoparticles reached 41°C in 10s and 44.5°C in 20s, exceeding the cell death temperature of 43°C. This proves that the nanoparticles can kill tumor cells at low power and in a short time.

[0065] Therefore, the present invention provides a copper ion carrier material with photothermal effect, a preparation method, and an anticancer drug composed of the copper ion carrier, which solves the problems of poor water solubility of existing copper ion carriers, low photothermal conversion efficiency, low near-infrared light energy, and difficulty in ultraviolet light penetrating into tissues and causing tissue damage when applying photothermal therapy.

[0066] In the description of this specification, the description with reference to the terms "an experimental example", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in conjunction with the experimental example or example are included in at least one experimental example or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same experimental example or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more experimental examples or examples in a suitable manner.

[0067] Finally, it should be noted that the above experimental examples are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred experimental examples, those skilled in the art should understand that they can still modify or replace the technical solution of the present invention with equivalents, and these modifications or equivalent replacements cannot cause the modified technical solution to deviate from the spirit and scope of the technical solution of the present invention.

Claims

1. A copper ion carrier material with photothermal effect, characterized in that: Its structural formula is as follows:

2. The method for preparing the copper ion carrier material with photothermal effect according to claim 1, characterized in that: The following steps are involved: S1: Mix diacetyl and concentrated hydrochloric acid in water, stir to react, add 4-methylthiosemicarbazide and continue to stir to react, and post-treat to obtain compound C6H 11 N3OS; S2: Compound C6H obtained in step S1 11 N3OS and 4,4-dimethylthiourea were dissolved in DMSO solvent, and glacial acetic acid was added for reaction. After post-treatment, compound C9H 18 N6S2; S3: Compound C9H obtained in step S2 18 N6S2 and 6-aminocaproic acid were dissolved in acetonitrile solvent for reaction, and then post-processed to obtain the compound S4: dissolving the compound obtained in step S3 and β-cyclodextrin in DMSO solvent, adding an activator and a condensing agent after mixing, reacting, and performing post-treatment to obtain a copper ion carrier material with a photothermal effect.

3. The method for preparing the copper ion carrier material with photothermal effect according to claim 2, characterized in that: In step S1, the post-treatment method is as follows: after the reaction, the yellowish solid is obtained by vacuum filtration, washed three times with distilled water, dissolved in 50-100 mL of ethanol, and vacuum filtered again to obtain a filtrate, the filtrate is evaporated to remove the solvent, and then vacuum dried to obtain compound C6H 11 N3OS.

4. The method for preparing the copper ion carrier material with photothermal effect according to claim 2, characterized in that: In step S2, the post-treatment method is as follows: 50-80 mL of distilled water is added to the obtained reaction solution, and the solution is placed in an ice water bath for 20-40 min. A yellow solid is obtained after filtration under reduced pressure, and then the yellow solid is washed with distilled water, ethanol, and ether in turn. The washed yellow solid is added with 100 mL of ethanol to dissolve again, and a light yellow solid is obtained after filtration under reduced pressure and then vacuum dried to obtain compound C9H 18 N6S2.

5. The method for preparing the copper ion carrier material with photothermal effect according to claim 2, characterized in that: In step S3, the post-treatment method is: adding 1% hydrochloric acid solution to precipitate solids, filtering under reduced pressure to obtain a filter cake, washing with acetonitrile and ether in turn, and then vacuum drying to obtain a compound 6. The method for preparing the copper ion carrier material with photothermal effect according to claim 2, characterized in that: In step S4, the post-treatment method is: vacuum filtration, adding the filtrate dropwise into acetone to precipitate, collecting the precipitate by centrifugation, dissolving it in DMSO solution, and then gradually adding the mixed solution dropwise into acetone to precipitate white flocculent precipitate, repeating three times, removing impurities, adding distilled water to dissolve and dialyze, and freeze-drying.

7. The method for preparing a copper ion carrier material with photothermal effect according to any one of claims 3 to 6, characterized in that: In step S1, the molar ratio of the 4-methylthiosemicarbazide to diacetyl is 1.0 mol:1.0-1.5 mol; in step S2, the compound C6H 11 The molar ratio of N3OS and 4,4-dimethylthiourea is 1.0 mol:1.0-1.5 mol; in step S3, the compound C9H 18 The molar ratio of N6S2 and 6-aminocaproic acid is 1.0:1.5-2.0; in step S4, the compound The molar ratio of β-cyclodextrin, activator and condensing agent is 1.0 mol: (2.0-3.0) mol: (2.0-5.0) mol: (2.0-5.0) mol.

8. The method for preparing the copper ion carrier material with photothermal effect according to claim 7, characterized in that: In step S1, after diacetyl and concentrated hydrochloric acid are mixed in water, the temperature of the stirring reaction is below 0°C, and the stirring reaction time is 20-190 minutes. After adding 4-methylthiosemicarbazide, the temperature of the stirring reaction is below 0°C, and the stirring reaction time is 20-80 minutes. In step S2, the amount of glacial acetic acid added is 4-11 drops, and the reaction is carried out at room temperature for 3-50 hours. In step S3, the reaction is carried out under nitrogen protection, the reaction temperature is 60-90°C, and the reaction time is 24-48 hours. In step S4, the reaction is carried out at 20-90°C and the reaction time is 4-48 hours.

9. The method for preparing the copper ion carrier material with photothermal effect according to claim 8, characterized in that: In step S1, the volume amount of concentrated hydrochloric acid is based on the compound The volume is 200mL / L; in step S3, the activator is one or more of DCC and EDC; the condensing agent is one or more of DMAP, HOBT, and DIEA; in step S4, the molecular weight of the β-cyclodextrin is calculated as a single sugar molecule 162, and the volume amount of DMSO is 30-50mL / g based on the mass of β-cyclodextrin.

10. An anticancer drug, characterized in that: Including Cu 2+ And the copper ion carrier material with photothermal effect as claimed in claim 1, Cu 2+ The nanoparticles are formed by combining with copper ion carrier materials through chelation. 2+ The targeted effect of Cu 2+ on the mitochondria of cells is then used to deliver near-infrared light, generating a temperature that can kill tumors. 2+ Increase intracellular Cu 2+ level, produce reactive oxygen species, induce tumor cell death and thus treat the disease.

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