CN109396457B

CN109396457B - Shape and size controllable gold nanoparticle and preparation method and application thereof

Info

Publication number: CN109396457B
Application number: CN201811482468.3A
Authority: CN
Inventors: 肖玉玲; 洪学传; 吴华萍; 唐琳; 曾小东
Original assignee: SUZHOU Institute OF WUHAN UNIVERSITY
Current assignee: SUZHOU Institute OF WUHAN UNIVERSITY
Priority date: 2018-12-05
Filing date: 2018-12-05
Publication date: 2022-02-15
Anticipated expiration: 2038-12-05
Also published as: CN109396457A

Abstract

The invention discloses a shape and size controllable gold nanoparticle and a preparation method and application thereof. The method adopts a seed growth method to synthesize water-soluble, monodisperse and different-morphology-size gold nanoparticles, including spheres, rods, dumbbells, bipyramids, cubes, stars and the like with branch structures, the series of the gold nanoparticles uses ascorbic acid, sodium borohydride or hydroquinone as a reducing agent, cetyl trimethyl ammonium bromide as a cationic surfactant and a stabilizing agent, and sodium citrate as a reducing agent and a stabilizing agent, and the gold nanoparticles with different sizes can be obtained by changing a seed solution, so that the fine regulation and control of the morphology and the particle size of the gold nanoparticles are realized, the yield is high, the purity is high, the water solubility is good, the biological toxicity is avoided, and the purification process is simple. Can be applied to the fields of photoacoustic imaging, photothermal therapy, biosensing and the like.

Description

Shape and size controllable gold nanoparticle and preparation method and application thereof

Technical Field

The invention belongs to the technical field of nano material preparation, relates to tumor imaging, photothermal therapy and the like in the field of biomedicine, and particularly relates to a preparation method of a series of nano gold particles with different shapes and sizes.

Background

Cancer has become a leading enemy of human health. Conventional treatment modalities include chemotherapy, radiation therapy, surgical resection, and the like. However, due to the challenges of poor patient compliance during chemotherapy, high surgical recurrence probability, damage to normal cells by radiotherapy, and the like, novel and effective cancer treatment strategies need to be researched. Targeted therapy is an emerging class of therapies that has evolved gradually from the late 90 s of the 20 th century and has achieved significant effects in the treatment of certain types of cancer. The nanometer material is used as a drug or gene transmission carrier, has the advantages of improving the water solubility and stability of the drug, reducing the toxicity of the drug, enhancing the curative effect of the drug, improving the distribution of the drug in vivo and the like, and develops rapidly in recent years.

Today, nano-gold shows huge potential in the biomedical field by virtue of unique physicochemical property and optical property thereof, and research of nano-gold also gets very extensive attention. The nano gold is a gold material with the grain diameter of 1nm-250nm, is easy to synthesize, has small toxicity and good biocompatibility, can accurately regulate and control the optical property of the nano gold, and is easy to be used for modifying medicines and targeting molecules. As nano metal particles, surface electrons can only vibrate in a nano size, thus generating a local plasma phenomenon, and when near infrared light with a proper wavelength is used for irradiation, the metal particles can absorb light energy and convert the light energy into heat energy, namely, a photothermal effect. And the nano gold is used as inert metal, and in an excitation area, because of the enhancement of a near-surface electromagnetic field, a Raman scattering signal absorbed by molecules is greatly enhanced compared with that of common Raman scattering. By utilizing the Surface Enhanced Raman Scattering (SERS) and local plasmon resonance (LSPR) effects of the nanogold, the nanogold becomes a research hotspot of current tumor treatment and early disease diagnosis. At present, the preparation of the nano gold particles is divided into two strategies, namely a top-down physical method and a bottom-up chemical method. The seed growth method is the most common method at present, and can further grow the gold core into the gold nano-particles with specific size and shape.

In order to rapidly and efficiently obtain nanogold with different shapes and properties, which can be used in the fields of tumor diagnosis and treatment such as photothermal therapy, photoacoustic imaging and the like, a universal and environment-friendly preparation method of nanogold particles is developed to meet new research requirements.

Disclosure of Invention

In order to overcome the defects in the prior art, the invention aims to synthesize a series of gold nanoparticles with different shapes and sizes of 50nm or 100nm by using a seed growth method, and the obtained gold nanoparticles have better water solubility and monodispersity and good biocompatibility and can be used for tumor photothermal therapy and photoacoustic imaging.

In order to achieve the above purpose, the invention provides the following technical scheme:

in a first aspect, a method for preparing gold nanoparticles with controllable shape and size is provided, which comprises the following steps:

(1) preparation of seed solution: dissolving a proper amount of stabilizer in deionized water, adding chloroauric acid, stirring uniformly, then adding a sodium borohydride solution prepared by ice water or adopting a thermal reduction mode to form a brown yellow or red solution, and keeping the temperature of 25-110 ℃ for reaction;

(2) preparation of growth solution: a. dissolving a certain amount of stabilizer in deionized water, mixing with chloroauric acid solution, and changing the solution from dark yellow to colorless;

or,

a', dissolving a certain amount of stabilizer in deionized water, mixing with chloroauric acid solution, and then adding a structure directing agent, a pH regulator and a reducing agent to change the solution from dark yellow to colorless;

(3) mixing the seed solution obtained in the step (1) with the growth solution obtained in the step (2), and reacting in a water bath at 29-95 ℃;

or,

mixing the seed solution obtained in the step (1) with the growth solution obtained in the step (2) to prepare a new seed solution, mixing the new seed solution with the growth solution obtained in the step (2), and keeping the new seed solution in a water bath at 29-95 ℃ for reaction;

(4) and after the reaction is finished, collecting, centrifuging and purifying to obtain the nano gold particles.

Preferably, in the above preparation method, the stabilizer in step (1) and step (2) is cetyl trimethyl ammonium bromide or sodium citrate; the structure directing agent in the step (2) is silver nitrate or potassium iodide, the pH regulator is hydrochloric acid, and the reducing agent is ascorbic acid or hydroquinone.

Preferably, in the above preparation method, the final concentration of chloroauric acid is 0.01-0.025mol/L, the final concentration of sodium borohydride is 0.01-0.1mol/L, the final concentration of cetyltrimethylammonium bromide is 0.0001-0.1mol/L, the final concentration of silver nitrate is 0.004-0.01mol/L, the final concentration of potassium iodide is 0.01-0.1mol/L, the final concentration of hydroquinone is 0.01-0.06mol/L, the final concentration of ascorbic acid is 0.01-0.1mol/L, the final concentration of sodium citrate is 0.0022-0.02mol/L, and the final concentration of hydrochloric acid is 0.5-1.5 mol/L.

Preferably, in the above preparation method, the optimal seed reaction time in step (1) is 1-4h, and the optimal growth reaction time in step (3) is 12-16 h.

In a second aspect, the nano gold particles obtained by the preparation method are provided, the morphology of the nano gold particles is any one of spherical, cubic, star-shaped, rod-shaped, dumbbell and bipyramid, the particle size is 50nm or 100nm respectively, and the total number of the nano gold particles is 12.

The twelve types of nano gold particles prepared by the invention have obvious difference of maximum absorption peaks through UV/Vis wavelength scanning, the absorption peaks and colors show changes along with different shapes and sizes, and the maximum characteristic absorption peak of an ultraviolet-visible-infrared spectrum is positioned at 400-900 nm.

Zeta-potential results before and after centrifugal purification of the prepared gold nanoparticles show that after the centrifugal purification, after the excessive hexadecyl trimethyl ammonium bromide in the system is removed, potentials are reduced, but absolute values are still larger than 30mV, which shows that after the excessive hexadecyl trimethyl ammonium bromide in the system is removed by purification, the stability is good.

In a third aspect, the application of the gold nanoparticles in tumor photothermal therapy or tumor photoacoustic imaging is provided.

The present invention uses cetyl trimethyl ammonium bromide or sodium citrate as stabilizer, silver nitrate and potassium iodide as structure directing agent, ascorbic acid, sodium borohydride or hydroquinone as reducing agent, hydrochloric acid as pH regulator, and adopts two-step method to obtain a series of 50nm and 100nm star-shaped nano gold with spherical, rod-shaped, dumbbell-shaped, double cone-shaped, cubic and branched structures by changing the dosage of various compounds and the volume of the first-step seed solution.

Compared with the known method for synthesizing the nanogold material, the method has the advantages of simple and feasible preparation process, mild experimental conditions, cheap and easily-obtained required experimental reagents, effectively controlled morphology and size of the synthesized nanogold, good water solubility, good monodispersity, good stability, no toxic or side effect proved by in vitro experiments and good biocompatibility. Can be used for photothermal therapy, tumor imaging and the like.

Drawings

FIG. 1 shows the corresponding UV-Vis spectra of the nanogold solution with different morphologies of 50nm and 100nm in the embodiment.

FIG. 2 shows Zeta potentials before and after purification of 12 nanogold in a specific implementation method.

FIG. 3 shows transmission electron microscope images of 50nm and 100nm spherical nanogold described in example 1, wherein a is 50nm, b is 100 nm.

FIG. 4 shows transmission electron micrographs of 50nm and 100nm cubic nanogold as described in example 2, a, 50nm, b, and 100 nm.

FIG. 5 shows transmission electron micrographs of star-shaped 50nm and 100nm nanogold as described in example 3, a, 50nm, b, and 100 nm.

FIG. 6 is the transmission electron microscope pictures of the rod-shaped nanogold of 50nm and 100nm described in example 4, a, 50nm, b, and 100 nm.

FIG. 7 is a transmission electron micrograph of 50nm and 100nm dumbbell-shaped nanogold, a, 50nm, b, 100nm, described in example 5.

FIG. 8 is transmission electron microscope pictures of 50nm and 100nm bipyramidal nanogold described in example 6, a, 50nm, b, 100 nm.

Fig. 9 shows the actual particle size of nanogold through TEM in all examples.

FIG. 10 shows the toxic effect of six nanogold at 50nm on HepG2 and LO2 cells in all examples.

FIG. 11 shows the toxic effect of six nanogold at 100nm on HepG2 and LO2 cells in all examples.

Fig. 12 is a photo-thermal imaging diagram of 100nm bipyramid nanogold during tumor photo-thermal treatment.

Fig. 13 is a tumor ultrasonic-photoacoustic imaging picture of 100nm cubic nano-gold.

Detailed Description

The features and advantages of the present invention will be further understood from the following detailed description taken in conjunction with the accompanying drawings. The examples provided are merely illustrative of the method of the present invention and do not limit the remainder of the disclosure in any way.

The concentrations in the following examples are all final concentrations.

Example 1: synthesis of 50nm and 100nm spherical nano gold

1) Preparation of seeds

Weighing a certain amount of sodium citrate trihydrate, dissolving the sodium citrate trihydrate in 150mL of first-grade water to prepare 2.2mmol/L, and adding HAuCl₄(concentration 25mmol/L) the solution was stirred vigorously in a water bath at 110 ℃ for 15 min. The color of the solution was observed to change from yellow to blue-gray, then to pink within 10min, to wine-red in about 30 min.

2) Preparation of growth solution

53mL of primary water, 2mL of sodium citrate (60mmol/L) and HAuCl were taken₄Preparing a solution of (25mmol/L), heating to 90 ℃, taking 55mL of the seed solution cooled to 90 ℃, mixing with the seed solution, and reacting in a water bath at 95 ℃ for a certain time. The size of the nano gold particles is increased along with the increase of the size of the nano gold particles, and spherical nano gold with the particle size of 50nm and 100nm can be formed.

Example 2: synthesis of 50nm and 100nm cubic nanogold

1) Preparation of 50nm cubic seeds

First, HAuCl is added₄(0.01mol/L) solution and cetyltrimethylammonium bromide were added to 10mL of primary water and shaken well for 5min, and the color of the solution was observed to change from light yellow to orange. Then adding the prepared NaBH at 25 DEG C₄(0.1mol/L) solution. Upon addition, a solution was observedThe color of (a) immediately changes from orange to brown.

2) Preparation of 50nm cubic growth solution

HAuCl was added to the aqueous cetyl trimethyl ammonium bromide solution at room temperature₄(0.01 mol/L). Then, a freshly prepared aqueous solution of ascorbic acid (0.1mol/L) was added to the mixture solution, the color of the solution immediately changed from orange to colorless, and the prepared seeds were dropped into the colorless liquid using a 5. mu.L micro syringe, reacted for 12 to 14 hours, and the solution was seen to appear deep red.

3) Preparation of 100nm cubic seed

0.25mL of HAuCl₄(0.01mol/L) of the aqueous solution was added to a mixed solution of cetyltrimethylammonium bromide (0.1 mol/L). Shaking for several minutes, adding ice water to prepare NaBH₄(0.1mol/L) aqueous solution, and then stirred at 28 ℃ for 1h in the absence of light.

4) Preparation of 100nm cubic seed-

The above gold seeds were diluted 10-fold and added to a solution containing 6mL of 0.1mol/L ascorbic acid, cetyltrimethylammonium bromide (0.1mmol/L) and HAuCl₄The growth was continued for 1h (0.01 mol/L).

5) Preparation of 100nm cubic growth solution

Seed ② is added into hexadecyl trimethyl ammonium bromide and HAuCl₄(0.01mol/L) and ascorbic acid (0.1mol/L), the total volume of the solution was 10 mL. And reacting for 12-14h in the dark.

Example 3: synthesis of 50nm and 100nm star shaped nano gold

1) Preparation of seeds

Adding HAuCl₄(0.01mol/L) and trisodium citrate (0.02mol/L) were added to the primary water, and the total volume of the mixed solution was 20 mL. Then adding 60 mu L of ice water prepared sodium borohydride NaBH under stirring₄Solution (0.1 mol/L). Adding NaBH₄The solution turns pink immediately after the reaction, and gold spherical seeds are formed after the reaction for 2 hours in a dark place.

2) Preparation of growth solution

Cetyl trimethyl ammonium bromide is weighed and dissolved in 9.5mL of primary water, and HAuCl is added₄(0.01 mol/L). The solution is yellowAnd changed to orange. First adding AgNO under the condition of violent stirring₃(0.01mol/L), and ascorbic acid (0.1mol/L) is then added. The orange solution turned into a clear colorless solution. Then, a certain amount of the seed solution is added into the colorless solution for reaction for a certain time.

Example 4: synthesis of 50nm and 100nm rod-like nanogold

1) Preparation of 50nm Bar-shaped seeds

Cetyl trimethyl ammonium bromide solution (0.1mol/L) and 0.01mol/L HAuCl₄And (4) mixing. Adding ice water prepared 0.01mol/L NaBH into the stirred solution₄The solution formed a brownish yellow solution and vigorous stirring of the seed solution was continued. The reaction was maintained at 25 ℃ for 2 h.

2) Preparation of 50nm rod-like growth solution

The temperature was kept constant at 29 ℃ by adding HAuCl to a solution of cetyltrimethylammonium bromide (0.1mol/L)₄(0.01mol/L), mixing thoroughly, adding AgNO₃(0.004mol/L) solution. Then, ascorbic acid (0.0788mol/L) solution was added as a mild reducing agent. The growth solution changed from dark yellow to colorless. mu.L of the seed solution was added to the growth solution. The color of the solution is gradually changed within 10-20 minutes, and the rod-shaped nano gold with the particle size of 50nm is obtained after the reaction for a certain time.

3) Preparation of 100nm rodlike seed

4) Preparation of 100nm gold rod seed

The temperature was kept constant at 29 ℃ by adding HAuCl to a solution of cetyltrimethylammonium bromide (0.1mol/L)₄(0.01mol/L), mixing thoroughly, adding AgNO₃(0.004mol/L) solution. Then, ascorbic acid (0.0788mol/L) solution was added as a mild reducing agent, and the solution turned from dark yellow to colorless. mu.L of seed (r) solution was added to the above colorless solution. After a certain time of reaction, the gold nanorod solution (10mL) was separated8000rpm 30min to remove the excessive silver salt, ascorbic acid and HCl in the growth solution, and redispersed in 2mL of cetyltrimethylammonium bromide solution (0.1mol/L) so that the concentration of gold nanorods is 2.5mmol/L, to obtain seeds for further growth, a solution of ②.

5) Preparation of 100nm rod-shaped growth solution

In AgNO₃Secondary growth of gold nanorods in the presence of a solution of cetyltrimethylammonium bromide (0.1mol/L) and HAuCl in a total volume of 10mL₄(0.01mol/L) mixing to fully complex gold salt, and then adding AgNO₃(0.004mol/L) and ascorbic acid (0.1 mol/L). Finally adding gold nanorod seeds and solution.

Example 5: synthesis of 50nm and 100nm dumbbell-shaped nanogold

1) Preparation of dumbbell seed solution I

Cetyl trimethyl ammonium bromide solution (0.1mol/L) and 0.01mol/L HAuCl₄And (4) mixing. Adding ice water prepared 0.01mol/L NaBH into the stirred solution₄The solution formed a brown-yellow solution and continued to stir vigorously. The reaction was maintained at 25 ℃ for 2 h.

2) Preparation of dumbbell seed solution 2

The temperature was kept constant at 29 ℃ and HAuCl was added to a solution of cetyltrimethylammonium bromide (0.1mol/L)₄(0.01mol/L), mixing thoroughly, adding AgNO₃(0.004mol/L) solution. Ascorbic acid (0.0788mol/L) was then added as a mild reducing agent. The growth solution changed from dark yellow to colorless. To the above solution, 12. mu.L of seed (r) solution was added. Seed solution is obtained after reaction.

3) Preparation of dumbbell growth liquid

Cetyl trimethyl ammonium bromide (0.1mol/L) was mixed with HAuCl₄(0.01mol/L) are mixed well to form complex gold salt, and then certain amount of KI (0.01mol/L) and ascorbic acid (0.1mol/L) are added. Finally, the solution of seeds (II) with different volumes is added. And in the presence of KI, the gold nanorods grow twice into dumbbell-shaped nanogold with the particle size of 50nm and 100 nm.

Example 6: synthesis of 50nm and 100nm biconical nano-gold

1) Preparation of seeds

Adding HAuCl₄(0.01mol/L) was mixed with an aqueous solution of cetyltrimethylammonium bromide (0.1 mol/L). Adding freshly prepared NaBH₄(0.1mol/L) an ice-water solution. The solution changed from orange to brown indicating seed particle formation. The seed solution was washed with water at 40 ℃ for one week in the dark. The synthesis of bipyramid nanogold cannot be achieved using freshly prepared seeds, which need to be aged for at least 7 days.

2) Preparation of growth solution

Adding HAuCl₄(0.01mol/L) was added to an aqueous solution of cetyltrimethylammonium bromide (0.1 mol/L). AgNO added with stirring₃(4mmol/L) followed by hydroquinone (60mmol/L) and the appropriate volume of seed solution. Protected from light and water bath at 40 ℃ for 12 h.

Example 7: cytotoxicity

The twelve kinds of gold nanoparticles described in this example were synthesized by adjusting the amount of various additives using a seed growth method, the particle sizes were respectively concentrated at 50nm and 100nm, and the gold nanoparticles described in this example had good stability and biocompatibility, and the toxicity of the gold nanoparticles described in this invention on human hepatoma cells (HepG2) and normal hepatocytes (L02) was determined using the MTT method.

Example 8: 100nm bipyramid nanogold tumor photothermal therapy

Injecting 200 mu L PBS solution containing 100nm bipyramid nanogold 200 microgram into tumor-bearing mice inoculated with 4T1 mouse breast cancer cells at 500mW/cm in right hind limb through tail vein²Under the continuous irradiation of laser with the power of 808nm, a thermal imaging camera shoots a whole body imaging picture of the mouse, referring to the attached figure 12 of the specification, and the temperature of the tumor part of the tumor-bearing mouse reaches 65 ℃ after the laser irradiation is carried out for 10 minutes. Tumor size was monitored over a long period of time and mice were found to have completely disappeared tumors after laser irradiation. The material of the invention has better application prospect in the aspect of tumor photothermal treatment.

Example 9: photoacoustic imaging of 100nm cubic nanogold for tumors

50 mu L of PBS solution containing 50 mu g of cubic nanogold with the length of 100nm is injected into tumor-bearing mice with breast cancer cells of 4T1 mice inoculated on the right hind limb through tumor injection, a Vevo LAZR small animal photoacoustic imaging system is adopted to shoot an imaging picture of tumor parts of the mice, see the attached figure 13 of the specification, and the tumor parts of the mice show obvious photoacoustic signals after the nanogold is injected. The material of the invention has better application prospect in the aspect of tumor photoacoustic imaging.

Claims

1. A preparation method of star-shaped gold nanoparticles with the particle sizes of 50nm or 100nm respectively is characterized by comprising the following steps:

(1) preparation of seeds

Adding HAuCl₄Adding trisodium citrate into the first-stage water, adding the mixed solution into the first-stage water in a total volume of 20mL, and adding 60 mu L of NaBH prepared by ice water into the mixed solution under stirring₄Solution, adding NaBH₄The solution immediately turns pink, and reacts for 2 hours in a dark place to form gold spherical seeds;

(2) preparation of growth solution

Cetyl trimethyl ammonium bromide is weighed and dissolved in 9.5mL of primary water, and HAuCl is added₄(ii) a The solution changes from yellow to orange, and AgNO is firstly added under the condition of vigorous stirring₃Then 0.1mol/L ascorbic acid is added, the orange solution becomes clear colorless solution, and then a certain amount of the seed solution in the step (1) is added into the colorless solution for reaction for a certain time;

wherein, HAuCl₄Has a final concentration of 0.01mol/L, NaBH₄Has a final concentration of 0.1mol/L, a final concentration of cetyltrimethylammonium bromide of 0.1mol/L, AgNO₃The final concentration of (A) is 0.01mol/L, the final concentration of ascorbic acid is 0.1mol/L, and the final concentration of trisodium citrate is 0.02 mol/L.

2. A method for preparing rod-shaped gold nanoparticles with the particle size of 50nm or 100nm respectively is characterized in that A, aiming at the rod-shaped gold nanoparticles with the particle size of 50nm, the method comprises the following steps:

(1) preparation of 50nm Bar-shaped seeds

Mixing cetyl trimethyl ammonium bromide solution with HAuCl₄Mixing, adding NaBH prepared by ice water into the stirred solution₄Solution to form brown yellowThe seed solution is stirred vigorously and kept reacting for 2 hours at 25 ℃;

(2) preparation of 50nm rod-like growth solution

The temperature was kept constant at 29 ℃ by adding HAuCl to a cetyltrimethylammonium bromide solution₄Mixing thoroughly, adding AgNO₃Adding an ascorbic acid solution serving as a mild reducing agent into the solution, wherein the growth solution is changed from dark yellow to colorless, adding 12 mu L of the seed solution obtained in the step (1) into the growth solution, and reacting for a certain time to obtain 50nm rod-shaped nanogold, wherein the color of the solution is gradually changed within 10-20 minutes;

wherein, HAuCl₄Has a final concentration of 0.01mol/L, NaBH₄Has a final concentration of 0.01mol/L, a final concentration of cetyltrimethylammonium bromide of 0.1mol/L, AgNO₃The final concentration of the ascorbic acid is 0.004mol/L, and the final concentration of the ascorbic acid is 0.0788 mol/L;

or,

B. aiming at the rod-shaped gold nanoparticles with the size of 100nm, the method comprises the following steps:

(1) preparation of 100nm rodlike seed

Mixing cetyl trimethyl ammonium bromide solution with HAuCl₄Mixing, adding NaBH prepared by ice water into the stirred solution₄The solution is formed into a brown yellow solution, the seed solution is continuously stirred vigorously and kept at 25 ℃ for reaction for 2 hours;

(2) preparation of 100nm gold stick seed

The temperature was kept constant at 29 ℃ by adding HAuCl to a cetyltrimethylammonium bromide solution₄Mixing thoroughly, adding AgNO₃Adding an ascorbic acid solution serving as a mild reducing agent into the solution, changing the solution from dark yellow to colorless, adding 12 mu L of seed firstly solution into the colorless solution, after reacting for a certain time, centrifuging 10mL of gold nanorod solution at 8000rpm for 30 minutes to remove excessive silver salt, ascorbic acid and HCl in the growth solution, and dispersing in 2mL of hexadecyl trimethyl ammonium bromide solution again to ensure that the concentration of the gold nanorods is 2.5mmol/L to obtain a gold nanorod seed secondly solution for further growth;

(3) preparation of 100nm rod-shaped growth solution

In AgNO₃Secondary growth of gold nano rod in the presence of 10mL of hexadecyl trimethyl ammonium bromide and HAuCl₄Mixing to complex the gold salt thoroughly, and adding AgNO₃Ascorbic acid and finally gold rod seed solution;

wherein, HAuCl₄Has a final concentration of 0.01mol/L, NaBH₄Has a final concentration of 0.01mol/L, a final concentration of cetyltrimethylammonium bromide of 0.1mol/L, AgNO₃The final concentration of (3) is 0.1mol/L, the final concentration of ascorbic acid in step (2) is 0.0788mol/L, the final concentration of ascorbic acid in step (3) is 0.5-1.5mol/L, and the final concentration of hydrochloric acid is 0.004 mol/L.

3. A preparation method of dumbbell nano-gold particles with the particle sizes of 50nm or 100nm respectively is characterized by comprising the following steps:

(1) preparation of dumbbell seed solution I

Mixing cetyl trimethyl ammonium bromide solution with HAuCl₄Mixing, adding NaBH prepared by ice water into the stirred solution₄Forming a brown yellow solution, continuously and violently stirring the solution, and reacting for 2 hours at 25 ℃;

(2) preparation of dumbbell seed solution 2

The temperature was kept constant at 29 ℃ and HAuCl was added to a solution of 0.1mol/L cetyltrimethylammonium bromide₄Mixing thoroughly, adding AgNO₃Adding ascorbic acid as a mild reducing agent into the solution, changing the growth solution from dark yellow to colorless, adding 12 mu L of seed solution I into the solution, and reacting to obtain seed solution II;

(3) preparation of dumbbell growth liquid

Cetyl trimethyl ammonium bromide and HAuCl₄Fully mixing to form complex gold salt, then adding a certain amount of KI and ascorbic acid, finally adding different volumes of seed ② solution, and secondarily growing the gold nanorods into dumbbell-shaped nano gold of 50nm and 100nm in the presence of KI;

wherein, HAuCl₄Has a final concentration of 0.01mol/L, NaBH₄Has a final concentration of 0.01mol/L, a final concentration of cetyltrimethylammonium bromide of 0.1mol/L, AgNO₃The final concentration of (2) was 0.0788mol/L and the final concentration of ascorbic acid was 0.1mol/L, KI was 0.01mol/L, and step (3) was 0.004 mol/L.

4. A preparation method of bipyramid nano-gold particles with the particle sizes of 50nm or 100nm respectively is characterized by comprising the following steps:

(1) preparation of seeds

Adding HAuCl₄Mixing with aqueous cetyl trimethyl ammonium bromide, adding freshly prepared NaBH₄The ice water solution changes from orange to brown to show that seed particles are formed, the seed solution is washed in water for one week at 40 ℃ in a dark place, the synthesis of the bipyramid nanogold cannot be realized by using the freshly prepared seeds, and the seeds need to be aged for at least 7 days;

(2) preparation of growth solution

Adding HAuCl₄Adding into aqueous solution of hexadecyl trimethyl ammonium bromide, adding AgNO under stirring₃Then adding hydroquinone and a proper volume of the seed solution obtained in the step (1), and keeping out of the sun and in a water bath at 40 ℃ for 12 hours;

wherein, HAuCl₄Has a final concentration of 0.01mol/L, NaBH₄Has a final concentration of 0.1mol/L, a final concentration of cetyltrimethylammonium bromide of 0.1mol/L, AgNO₃The final concentration of (A) is 0.004mol/L, and the final concentration of hydroquinone is 0.06 mol/L.

5. A preparation method of cubic gold nanoparticles with the particle size of 100nm is characterized by comprising the following steps:

(1) preparation of 100nm cubic seed

0.25mL of HAuCl₄Adding the aqueous solution into a mixed solution of hexadecyl trimethyl ammonium bromide, shaking for several minutes, and adding NaBH prepared by ice water₄Stirring the aqueous solution at 28 ℃ in the dark for 1 h;

(2) preparation of 100nm cubic seed-

The above gold seeds were diluted 10-fold and added to a solution containing 6mL of ascorbic acid, cetyltrimethylammonium bromide and HAuCl₄Continuously growing for 1 h;

(3) preparation of 100nm cubic growth solution

Seed ② is added into hexadecyl trimethyl ammonium bromide and HAuCl₄And ascorbic acid, wherein the total volume of the solution is 10mL, and the solution is subjected to light-shielding reaction for 12-14 h;

wherein, HAuCl₄Has a final concentration of 0.01mol/L, NaBH₄The final concentration of (A) was 0.1mol/L, the final concentration of cetyltrimethylammonium bromide was 0.1mol/L, and the final concentration of ascorbic acid was 0.1 mol/L.

6. A preparation method of spherical nano gold particles with the particle size of 50nm or 100nm is characterized by comprising the following steps:

(1) preparation of seeds

Weighing a certain amount of sodium citrate trihydrate, dissolving the sodium citrate trihydrate in 150mL of first-grade water to prepare 2.2mmol/L, and adding HAuCl₄The solution is stirred vigorously in a water bath at 110 ℃ for 15min, and the color of the solution can be observed to change from yellow to blue-gray, then to pink within 10min and to wine-red within about 30 min;

(2) preparation of growth solution

Taking 53mL of primary water and 2mL of primary water containing sodium citrate and HAuCl₄Preparing the solution into a solution, heating to 90 ℃, taking 55mL of the seed solution cooled to 90 ℃, mixing with the seed solution, reacting in a water bath at 95 ℃ for a certain time, and increasing the size of the nano-gold particles to form spherical nano-gold of 50nm and 100 nm;

wherein, HAuCl₄The final concentration of (3) is 0.025mol/L, and the final concentration of sodium citrate in the step (2) is 0.06 mol/L.

7. The gold nanoparticles obtained by the production method according to any one of claims 1 to 6.

8. Use of the gold nanoparticles of claim 7 for the preparation of a medicament for tumor photothermal therapy or tumor photoacoustic imaging.