CN107961375B

CN107961375B - Metal sulfide nano material and preparation method and application thereof

Info

Publication number: CN107961375B
Application number: CN201710996469.9A
Authority: CN
Inventors: 谷战军; 张潇; 董兴华; 赵宇亮
Original assignee: Institute of High Energy Physics of CAS
Current assignee: Institute of High Energy Physics of CAS
Priority date: 2017-10-24
Filing date: 2017-10-24
Publication date: 2020-12-08
Anticipated expiration: 2037-10-24
Also published as: CN107961375A

Abstract

The invention discloses a metal sulfide nano material and a preparation method and application thereof, wherein the metal sulfide nano material comprises a bismuth sulfide nanorod, a high polymer material and a nitric oxide donor, wherein the high polymer material and the nitric oxide donor are coated on the surface of the bismuth sulfide nanorod, the high polymer material is polyoxyethylene sorbitan laurate Tween-20, and the nitric oxide donor comprises BNN. The metal sulfide nano material can convert light energy into heat, promotes a nitric oxide donor to decompose and release nitric oxide by utilizing a photothermal conversion process, can simultaneously realize controllable release and photothermal treatment of nitric oxide, can reduce the self-protection effect of tumor cells in the thermal treatment process, and can obviously improve the tumor treatment effect. Therefore, the invention overcomes the defects of the traditional tumor thermotherapy method and is suitable for tumor therapy with complex requirements.

Description

Metal sulfide nano material and preparation method and application thereof

Technical Field

The invention belongs to the technical field of nano materials, and particularly relates to a metal sulfide nano material as well as a preparation method and application thereof.

Background

Since 1992 Nitric Oxide (NO) was evaluated as an annual star molecule by the Science journal, a series of studies on NO have been conducted. Researchers have found that NO can act as a messenger molecule in the body and plays an extremely important role in a variety of physiological regulatory processes, such as neurotransmission, vasodilation, hormone secretion, platelet aggregation, lesion repair, immunomodulation, and the like. Clinically, nitric oxide donor drugs are commonly used to treat paroxysmal angina, coronary heart disease, and the like.

Currently, the following types of donors that can release NO are commonly used: sodium nitroprusside, nitric acid \ nitrous acid ester, S-nitrosothiol and N-azoenediol. A common feature of these widely used classes of NO donors is the spontaneous release of NO in the organism. However, nitric oxide itself is chemically active, has a half-life of only about 5s, and its physiological action is closely related to concentration. Therefore, the spontaneous sustained release type NO donor drug needs to be strictly controlled in the practical application, and the therapeutic effect is unstable due to various factors. In order to overcome the defects of the spontaneous sustained release type NO donor, researchers develop a series of controlled release type NO donors, such as Sambusa black salt (RBS), metal NO complexes, NO modified nanoparticles and the like. Most of the controlled release NO donors are photoresponsive materials and can release nitric oxide molecules under the irradiation of specific wavelengths. However, most of these materials are sensitive to uv/visible light, which has insufficient penetration depth and may have some side effects in vivo. In contrast, near infrared light (NIR) has a strong penetration ability and low phototoxicity in the body of a living organism. Therefore, the research on the near infrared light controlled release NO donor is of great significance.

With the development of nitric oxide donors, researchers have used nitric oxide in the field of tumor therapy. Nitric oxide is also a free radical that can cause the nitration/nitrosation of biologically active molecules, destroying their structure and function. Meanwhile, nitric oxide also participates in cell signal pathway regulation and various cell physiological processes such as cell proliferation, cell apoptosis and autophagy. A concentration of nitric oxide can directly kill tumor cells or increase the sensitivity of tumor cells to other therapeutic approaches. Of particular interest, is the synergy of nitric oxide with conventional oncological treatment strategies, such as the synergistic relationship between nitric oxide and chemotherapy, radiation therapy, and thermal therapy. Therefore, it is desired to obtain a nano material capable of performing photothermal tumor therapy and controllably releasing nitric oxide, and to deeply study the tumor therapy effect thereof.

Disclosure of Invention

The invention aims to provide a metal sulfide nano material with photothermal conversion and nitric oxide release functions, a preparation method thereof and application in tumor treatment.

The technical scheme adopted by the invention is as follows:

the metal sulfide nano material comprises a bismuth sulfide nanorod, a high polymer material and a nitric oxide donor, wherein the high polymer material and the nitric oxide donor are coated on the surface of the bismuth sulfide nanorod, the high polymer material is polyoxyethylene sorbitan laurate Tween-20, and the nitric oxide donor comprises BNN.

The length of the bismuth sulfide nanorod is 10-100 nm, and the length-diameter ratio of the bismuth sulfide nanorod is 5-20.

The hydrated particle size of the metal sulfide nano material is 20-150 nm.

The potential of a water system of the metal sulfide nano material is-5 to-30 mV.

The invention also discloses a preparation method of the metal sulfide nano material, which comprises the following steps:

step 1, adding an organic solvent into bismuth salt serving as a precursor, and heating for reaction for a period of time to obtain a solution;

step 2, adding sulfur powder dissolved in oleylamine into the solution obtained in the step 1, continuing to heat and react for a certain time, and cooling to prepare a bismuth sulfide nanorod;

step 3, dissolving the bismuth sulfide nanorod obtained in the step 2 in cyclohexane, adding Tween-20 and deionized water, heating and evaporating to remove cyclohexane to obtain a Tween-20 modified bismuth sulfide nanorod;

and 4, selecting a nitric oxide donor, uniformly mixing the nitric oxide donor and the bismuth sulfide nanorod obtained in the step 3 in ethanol, and stirring to obtain the metal sulfide nanomaterial.

In the step (1), the bismuth salt is bismuth nitrate, bismuth chloride or bismuth dodecaoctoate; the organic solvent is one or more of oleic acid, oleylamine and octadecene; the molar concentration of bismuth in the solution in the step (1) is 0.05-0.5 mol/L; the heating temperature in the step (1) is 100-200 ℃; the reaction time in the step (1) is 10-30 min.

In the reaction in the step (2), the molar ratio of bismuth to sulfur is 1 (1-5); the heating temperature in the step (2) is 150-200 ℃; the reaction time in the step (2) is 1-10 min.

In the step (3), the ratio of the concentration of the bismuth sulfide nano-rods to the volume of Tween-20 is 1:2 to 1: 5; the volume ratio of cyclohexane to deionized water in the reaction is 1:2 to 1: 5.

The nitric oxide donor in the step (4) is any one or more of BNN and derivatives thereof, and after the nitric oxide donor is added into the ethanol, the concentration of the nitric oxide donor is 0.1-4.0 mmol/L; and (4) stirring for 4-24 hours.

The invention also discloses an application method of the metal sulfide nano material, which combines the metal sulfide nano material with a method for treating tumors to inhibit the growth of tumor cells.

Due to the adoption of the technical scheme, the invention has the beneficial effects that:

1. the metal sulfide nano material can respond to near infrared light to release nitric oxide, and breaks through the limitation that the traditional light-controlled nitric oxide release material can only respond to ultraviolet light or visible light. By using the metal sulfide nano material, the absorption peak is shifted to a near infrared window, so that the penetration depth of laser in a living body can be effectively increased, the absorption of living tissues to the laser is reduced, and the damage to normal tissues is reduced.

2. The metal sulfide nano material has a good photothermal conversion function, can realize effective combination of thermal therapy and nitric oxide, plays a role in synergy, greatly improves the traditional photothermal treatment efficiency, and obtains an optimal tumor treatment effect.

Drawings

Fig. 1 is a schematic structural diagram of a metal sulfide nanomaterial of the present invention.

FIG. 2 is a transmission electron microscope image of the metal sulfide nano-material of the present invention.

FIG. 3 is an X-ray diffraction spectrum of the metal sulfide nano-material of the present invention.

FIG. 4 is an ultraviolet absorption spectrum of the metal sulfide nano-material of the present invention.

FIG. 5 is an infrared absorption spectrum of the metal sulfide nano-material of the present invention.

FIG. 6 is a graph of temperature changes of metal sulfide nanomaterials with different concentrations under near-infrared laser illumination.

FIG. 7 is a schematic diagram of the concentration of nitric oxide released by the metal sulfide nanomaterial in the present invention.

FIG. 8 is a schematic diagram showing the effect of the metal sulfide nano-material on the cell viability of BEL-7402.

FIG. 9 is a schematic diagram of the effect of the metal sulfide nanomaterial on the apoptosis and necrosis promotion of BEL-7402 cells under the near-infrared laser illumination condition.

FIG. 10 is an infrared thermal imaging graph and a temperature change curve graph of a tumor part under an illumination condition after the metal sulfide nano material is administered into a tumor of a tumor-bearing mouse.

FIG. 11 is a graph showing tumor suppression results of combination of thermal therapy and nitric oxide after intratumoral administration of the metal sulfide nanomaterial of the present invention to tumor-bearing mice.

Detailed Description

The present invention will be described in further detail with reference to the following drawings and specific examples, but the present invention is not limited to these examples. The reagents or test instruments used in the following examples are commercially available unless otherwise specified.

As shown in fig. 1 and 2, a metal sulfide nano-material includes a bismuth sulfide nanorod, and a polymer material and a nitric oxide donor coated on the surface of the bismuth sulfide nanorod, wherein the polymer material is polyoxyethylene sorbitan laurate Tween-20, and the nitric oxide donor is one or more of bis-N-nitro-so compound (BNN for short) and its derivatives. .

The length-diameter ratio of the bismuth sulfide nanorod is 5-20, such as 5,8,10,15 and 20.

The length of the bismuth sulfide nanorod is 10-100 nm, such as 10nm, 20nm, 40nm, 55nm, 65nm, 80nm, 90nm or 100 nm.

The loading of the nitric oxide donor is 5% to 100% (mass percent), for example 5%, 10%, 20%, 40%, 50%, 65%, 80%, 90% or 100%, based on the weight of the metal sulfide nanomaterial.

The hydrated particle size of the metal sulfide nano material is 20-150 nm, such as 20nm, 23nm, 35nm, 48nm, 50nm, 63nm, 75nm, 88nm, 100nm, 123nm, 135nm, 140nm or 150 nm.

The potential of the water system of the metal sulfide nano material is-5 to-30 mV, such as-5 mV, -8mV, -11mV, -14mV, -17mV, -20mV, -23mV, -26mV or-30 mV.

The invention also discloses a preparation method of the metal sulfide nano material, which comprises the following steps: the method comprises the following steps:

step 1, adding an organic solvent into bismuth salt serving as a precursor, and heating for reaction for a period of time to obtain a solution; in this step, the bismuth salt is bismuth nitrate, bismuth chloride or bismuth dodecaoctoate; the organic solvent is one or more of oleic acid, oleylamine and octadecene; the molar concentration of bismuth element in the solution obtained by the step is 0.05-0.5 mol/L, such as 0.05mol/L, 0.1mol/L, 0.2mol/L, 0.3mol/L, 0.4mol/L or 0.5 mol/L; the heating temperature in this step is 100 to 200 ℃, for example, 100 ℃, 120 ℃, 140 ℃, 170 ℃, 180 ℃ or 200 ℃; the reaction time in this step is 10-30 min, such as 10min, 20min or 30 min;

step 2, adding sulfur powder dissolved in oleylamine into the solution obtained in the step 1, continuing to heat and react for a certain time, and cooling to prepare a bismuth sulfide nanorod; in the reaction in this step, the molar ratio of bismuth element to sulfur element is 1 (1-5), for example, 1:1, 1: 2. 1:3, 1:4 or 1: 5; the heating temperature in this step is 150 to 200 ℃, for example 150 ℃, 160 ℃, 170 ℃, 180 ℃ or 200 ℃; the reaction time in the step (2) is 1-10 min, such as 1min, 3min, 6min, 8min or 10 min.

Step 3, dissolving the bismuth sulfide nanorod obtained in the step 2 in cyclohexane, adding Tween-20 and deionized water, heating and evaporating to remove cyclohexane to obtain a Tween-20 modified bismuth sulfide nanorod; in the step (3), the ratio of the concentration (mg/mL) of the bismuth sulfide nanorods to the volume (μ L) of Tween-20 is 1:2 to 1:5, such as 1:2, 1:3, 1:4 or 1: 5; the volume ratio of cyclohexane to deionized water in the reaction is 1:2 to 1:5, such as 1:2, 1:3, 1:4, or 1: 5;

step 4, selecting a nitric oxide donor, uniformly mixing the nitric oxide donor and the bismuth sulfide nanorod obtained in the step 3 in ethanol, and stirring to obtain a metal sulfide nano material; the nitric oxide donor in the step (4) is BNN and derivatives thereof, and after the nitric oxide donor is added into the ethanol, the concentration of the nitric oxide donor is 0.1-4.0 mmol/L, such as 0.1mmol/L, 1.5mmol/L, 3.3mmol/L or 4.0 mmol/L; the stirring time in the step (4) is 4-24 h, such as 4h, 6h, 15h, 20h or 24 h.

The following is a detailed description of the preparation method of the metal sulfide nanomaterial by using specific examples.

Example 1:

(1) 3mmol of BiCl₃Adding the mixture into a 100mL three-neck round-bottom flask, adding 10mL oleic acid and 10mL oleylamine, adding a stirrer, stirring, heating to 170 ℃, and reacting for 30min to obtain a reaction system A;

(2) dissolving 10mmol of elemental sulfur in 5mL of oleylamine, and performing ultrasonic treatment to fully dissolve the elemental sulfur to obtain a solution I;

(3) quickly adding the solution I into the reaction system A, and continuously reacting for 10min at 170 ℃ to obtain a reaction system B;

(4) stopping the reaction, after the reaction system B is cooled to room temperature, transferring the system B into a centrifuge tube, centrifuging for 3min at the rotating speed of 8000 rpm, and then taking the precipitate to be suspended in 20mL of cyclohexane to prepare a solution II;

(5) taking 10mL of the solution II, adding 100 mu L of Tween-20, adding 30mL of deionized water, carrying out ultrasonic treatment for 30min, heating in a water bath to 70 ℃, and stirring until the solution is clear; centrifuging for 10min at a rotating speed of 12000 r/min, collecting the Tweeen-20 modified bismuth sulfide nanorod, and freeze-drying for later use;

(6) preparing 2mmol/L BNN ethanol solution III. Weighing 10mg of Tween-20 modified bismuth sulfide nanorod, adding 10mL of solution III, stirring for 12h in a dark place, centrifuging at 12000 r/min for 10min, and collecting precipitate to obtain the metal sulfide nanomaterial.

The schematic structural diagram of the metal sulfide nanomaterial prepared by the above example 1 is shown in fig. 1, and comprises tween-20 modified bismuth sulfide nanorods and nitric oxide donor BNNs adsorbed on the surface of the nanorods.

The metal sulfide nanomaterial obtained in example 1 was characterized by transmission electron microscopy (FEI Tecnai G2F20), and as a result, it was shown in fig. 2 that the material had a rod shape, a length of about 70nm, and a width of about 7 nm.

The metal sulfide nanomaterial obtained in example 1 was characterized by XRD using an X-ray diffractometer (Bruker D8), and as a result, as shown in fig. 3, it was found that the diffraction peak of the nanomaterial coincided with the diffraction peak of the standard spectrum of bismuth sulfide (represented by JCPDS 17-0320 in fig. 3, which is the XRD diffraction spectrum of the standard bismuth sulfide crystal in the database), and it was thus determined that the nanomaterial obtained contained bismuth sulfide.

The metal sulfide nano-material obtained in example 1 was characterized by using an ultraviolet-visible spectrometer (Hitachi U-3900), and the result is shown in FIG. 4, from which it can be seen that the material has absorption at a wavelength of 808nm, which indicates that the material can absorb light at a wavelength of 808 nm. Using this property, the thermal effect of the 808nm laser on the material can be analyzed in combination.

The metal sulfide nanomaterial obtained iN example 1 was characterized by an infrared spectrometer (Nicolet iN10, Thermo Fisher) and the results are shown iN FIG. 5, 1512cm^-1Peak corresponding to O ═ N bond; 1454cm^-1Corresponding to the vibration peak of the O-N bond, the characteristic peak of BNN appears in the infrared spectrogram.

From the above characterization results, it can be concluded that the bismuth sulfide nanomaterial loaded with nitric oxide donor BNN is prepared according to the present invention.

The photothermal conversion effect of the metal sulfide nanomaterial prepared in example 1 was measured as follows:

1mL of the metal sulfide nano-material with different concentrations is put into a cuvette with the diameter of 1cm, and 1W/cm is used²808nm continuous laser (spacious connet type in the upper sea) for 10 minutes while monitoring the temperature change of the solution in the cuvette using a near infrared imager (FLIR thermam E40).

As shown in FIG. 6, it is understood that the temperature of the nanomaterial solutions of different concentrations gradually increased under the laser irradiation of 808nm, indicating that the metal sulfide nanomaterial of the present invention has a good photothermal conversion function.

The performance of the metal sulfide nano-material prepared in example 1 for releasing nitric oxide under Near Infrared (NIR) irradiation is evaluated as follows:

3mL of the metal sulfide nanomaterial was placed in a 1cm cuvette, the nanomaterial in the cuvette was irradiated with 808nm continuous lasers (of the type Hangyonnet, Shanghai) of different powers for 15 minutes, 200. mu.L of the solution was taken out at intervals and centrifuged to obtain a supernatant, and the concentration of nitric oxide in the supernatant was measured using NO fluorescent probe 2,3-Diaminonaphthalene (DAN, Sigma).

As shown in fig. 7, it can be seen from fig. 7 that the metal sulfide nanomaterial can effectively release nitric oxide under the irradiation of a 808nm continuous laser.

The following is a measurement of the effect of the metal sulfide nanomaterial of the present invention on cell viability, taking the metal sulfide nanomaterial prepared in example 1 as an example, the method is as follows:

(1) cell culture

Placing BEL-7402 cell (human liver cancer cell) and DMEM liquid culture medium containing 10% fetal calf serum at 37 deg.C and CO₂Cell culture chamber with 5% concentration.

(2) Cell viability assay

Cells were seeded in 96-well plates at 5000 cells/well density. After 12 hours of attachment, DMEM liquid medium (containing 10% fetal bovine serum) containing the nanomaterial at concentrations of 0, 10, 20, 40, 80ppm (as bismuth element) was added. After 24 hours of treatment, the medium was removed, 100 μ L of cell culture medium containing 10% CCK-8 was added to each well, incubated for 1 hour in an incubator, absorbance at 450nm was measured on a microplate reader, absorbance of blank solution was subtracted from absorbance of each group using 600nm as the reference wavelength, the absorbance of each well was divided by the absorbance of the control group as cell viability, and 6 parallel wells were placed in each group.

FIG. 8 shows the effect of the metal sulfide nanomaterial of the present invention on the cell viability of BEL-7402, which is greater than 90% at different concentrations, indicating that the metal sulfide nanomaterial of the present invention is not toxic to BEL-7402 cells.

The killing effect of the metal sulfide nano material used for thermal therapy and nitric oxide synergistic therapy on human liver cancer cells BEL-7402 is determined, and the specific determination method is as follows:

(1) cell culture

Placing BEL-7402 cells and DMEM liquid medium containing 10% fetal calf serum at 37 deg.C and CO₂Cell culture chamber with 5% concentration.

(2) Apoptosis detection

Inoculating the cells cultured in step (1) into 6-well plates, 100000 cells per well. After 12 hours of attachment, DMEM liquid medium (containing 10% fetal bovine serum) containing 80ppm (as bismuth) of metal sulfide nanomaterial was added and incubated for 12 hours. The medium was removed, the cells were trypsinized, the supernatant was discarded by centrifugation at 1200 rpm, the cells were resuspended in PBS buffer (phosphate buffered saline), and the washing was repeated three times, each at a power density of 1.0W cm^-2The cell pellet was irradiated with the laser for 8min, washed three times with PBS buffer, stained with Annexin V-FITC/PI kit (apoptosis detection kit), and then detected with a flow cytometer. Ten thousand cells were collected and partitioned, and the percentage of cells in each region was counted.

As can be seen from FIG. 9, the metal sulfide nano material of the present invention can cause apoptosis and necrosis, and the effect is better than the thermotherapy effect using a pure bismuth sulfide material.

The influence of the metal sulfide nanomaterial of the present invention on the change in temperature of the tumor site of a tumor-bearing mouse is examined below, and the metal sulfide nanomaterial prepared in example 1 is used as an example, and the method is as follows:

feeding metal sulfide nano material into tumor of tumor-bearing mouse, and then using a laser with the wavelength of 808nm to make the laser to be 0.3W/cm²Irradiating the tumor site with the power of (1) for 10min so as to irradiate only the laser without the nanomaterialThe tumor-bearing mice of (1) were used as a control group, and the temperature rise at the tumor site of the mice was observed. The results are shown in fig. 10, from which it is apparent that the tumor site of the tumor-bearing mice which supply the metal sulfide nanomaterial intratumorally has a significant temperature-raising effect, while the tumor site temperature of the control mice is substantially unchanged.

The invention also discloses a pharmaceutical composition, which comprises the metal sulfide nano material and a drug loaded on the metal sulfide nano material. Based on the weight of the metal sulfide nano material, the drug loading rate of the pharmaceutical composition is 5-100 weight percent, such as 5, 10, 40, 65, 80 or 100. The drug is a nitric oxide donor comprising any one or more of BNN and its derivatives.

The tumor inhibiting effect of the metal sulfide nanomaterial of the present invention is examined below, and taking the metal sulfide nanomaterial prepared in example 1 as an example, the method is as follows:

(1) tumors were inoculated into the right hind leg of nude mice, and the number of cells required for each tumor inoculation was 5X 10⁶BEL-7402 cells. When the tumor volume reaches 100mm³The treatment experiments were performed on the left and right.

(2) Preparing the metal sulfide nano material into 4mg/mL PBS solution, injecting 20 mu L of the solution in tumor, and using a laser with the wavelength of 808nm and a 0.3W/cm²The tumor site was irradiated for 10 min. The tumor size was measured with a vernier caliper the next day after laser irradiation, and then every two days, and was monitored for two weeks. Mice were then sacrificed, tumors were removed and weighed, photographed, and set for PBS buffer group, laser irradiation group (NIR) alone, bismuth sulfide nanomaterial group (Bi) alone₂S₃) Individual group of metal sulfide nanomaterials (BNN-Bi)₂S₃) Thermal therapy set (Bi)₂S₃+ NIR) and hyperthermiaSynergistic group with nitric oxide (BNN-Bi)₂S₃+NIR)。

Fig. 11 shows the tumor volume results of different treatment groups, and it can be seen from the graph that the metal sulfide nanomaterial of the present invention can be used for the synergistic treatment of hyperthermia and nitric oxide, and the tumor growth is obviously inhibited, which is better than that of the bismuth sulfide material hyperthermia group alone.

The specific embodiments described herein are merely illustrative of the spirit of the invention. Various modifications or additions may be made to the described embodiments or alternatives may be employed by those skilled in the art without departing from the spirit or ambit of the invention as defined in the appended claims.

Claims

1. The metal sulfide nano material is characterized by comprising a bismuth sulfide nanorod, a high polymer material and a nitric oxide donor, wherein the high polymer material and the nitric oxide donor are coated on the surface of the bismuth sulfide nanorod, the high polymer material is polyoxyethylene sorbitan laurate Tween-20, and the nitric oxide donor comprises BNN; the length of the bismuth sulfide nanorod is 10-100 nm, and the length-diameter ratio of the bismuth sulfide nanorod is 5-20;

the hydrated particle size of the metal sulfide nano material is 20-150 nm;

2. A method for preparing the metal sulfide nanomaterial of claim 1, the method comprising the steps of:

step (1), bismuth salt is taken as a precursor, an organic solvent is added, and heating reaction is carried out for a period of time to obtain a solution;

step (2), adding sulfur powder dissolved in oleylamine into the solution obtained in the step (1), continuing to heat and react for a certain time, and cooling to prepare bismuth sulfide nanorods;

step (3), dissolving the bismuth sulfide nanorod obtained in the step (2) in cyclohexane, adding Tween-20 and deionized water, heating and evaporating to remove cyclohexane, and obtaining a Tween-20 modified bismuth sulfide nanorod;

and (4) selecting a nitric oxide donor, uniformly mixing the nitric oxide donor and the bismuth sulfide nano-rod obtained in the step (3) in ethanol, and stirring to obtain the metal sulfide nano-material.

3. The method for preparing a metal sulfide nano material according to claim 2, wherein in the step (1), the bismuth salt is bismuth nitrate, bismuth chloride or bismuth dodecaoctoate; the organic solvent is one or more of oleic acid, oleylamine and octadecene; the molar concentration of bismuth in the solution in the step (1) is 0.05-0.5 mol/L; the heating temperature in the step (1) is 100-200 ℃; the reaction time in the step (1) is 10-30 min.

4. The method for preparing the metal sulfide nano material according to claim 2, wherein in the reaction in the step (2), the molar ratio of bismuth to sulfur is 1 (1-5); the heating temperature in the step (2) is 150-200 ℃; the reaction time in the step (2) is 1-10 min.

5. The method for preparing a metal sulfide nano material according to claim 2, wherein in the step (3), the ratio of the concentration of the bismuth sulfide nano rods to the volume of Tween-20 is 1:2 to 1: 5; the volume ratio of cyclohexane to deionized water in the reaction is 1:2 to 1: 5.

6. The method for preparing a metal sulfide nanomaterial according to claim 2, wherein the nitric oxide donor in the step (4) is BNN, and after the nitric oxide donor is added into the ethanol, the concentration of the nitric oxide donor is 0.1-4.0 mmol/L; and (4) stirring for 4-24 hours.

7. Use of the metal sulfide nanomaterial of claim 1 in preparation of antitumor drugs.