A kind of hollow network gold nanoparticles and its preparation method and application

Abstract

The present invention discloses a hollow reticular gold nanoparticle, a preparation method thereof and an application thereof. The preparation method comprises the following steps: adding polyvinylpyrrolidone into a gold source solution, adding isooctanol after ultrasonic dispersion, then dropwise adding an alkali solution under stirring conditions, mixing evenly, and carrying out a hydrothermal reaction. The preparation method provided by the present invention is simple and feasible, has low requirements for equipment, uses less organic solvents, is environmentally friendly, and for the first time synthesizes a hollow reticular gold nanoparticle with a novel morphology by using the preparation method. The hollow reticular gold nanoparticle with the novel morphology has strong absorption in the second near-infrared region and can be used for preparing products for tumor photothermal therapy.

Description

Technical Field

[0001] The present invention relates to the technical field of nanomaterial preparation. More specifically, it relates to a hollow network gold nanoparticle and its preparation method and application. Background Art

[0002] In recent years, photothermal therapy (PTT) has attracted extensive interest from researchers in the field of tumor treatment as a minimally invasive therapy. The principle of photothermal therapy is to use a material with a high photothermal conversion efficiency as a photothermal conversion agent, and then utilize the enhanced permeability and retention effect (EPR effect) to make it accumulate at the tumor site. Under the irradiation of an external light source, the photothermal conversion agent can convert light energy into heat energy, causing the temperature of the tumor site to rise, leading to the necrosis of tumor cells, thereby achieving the purpose of treating tumors.

[0003] Currently, the light source used for photothermal therapy is generally near-infrared light, which refers to the electromagnetic wave with a wavelength between visible light and mid-infrared light. Near-infrared light can be further divided into near-infrared region I and near-infrared region II. Near-infrared region I generally refers to near-infrared light with a wavelength range of 760nm - 1000nm, and near-infrared region II generally refers to near-infrared light with a wavelength above 1000nm. Since near-infrared light has a longer wavelength and weaker scattering, its penetration ability in biological tissues is very strong, and it can reach deeper tissues. Compared with light in other wavelength bands, near-infrared light causes less damage to the human body. Especially for the light in near-infrared region II with a longer wavelength and stronger diffraction ability, the damage to the human body is even smaller. These advantages make near-infrared light an optical window for treating biological tissues. Therefore, seeking materials with good optical properties in the near-infrared region, especially near-infrared region II, and applying them to the biomedical field has also become the goal of many researchers.

[0004] In recent years, gold nanomaterials, as an emerging material, have shown many excellent properties, such as good biocompatibility, water solubility, and photostability. Among them, the most remarkable is its tunable surface plasmon resonance property in the near-infrared region. Surface plasmon resonance (SPR) is a phenomenon that occurs on the metal surface. Specifically, when light irradiates the metal, an evanescent wave will be generated on the metal surface. If the wavelength of the evanescent wave matches the plasma wave of the metal itself, the two will resonate, resulting in a large amount of the incident light energy being absorbed by the metal and the intensity of the reflected light being greatly reduced. Due to the surface plasmon resonance property of gold nanomaterials in the near-infrared region, they have a strong absorption in the near-infrared region. Therefore, gold nanomaterials can be used for the photothermal treatment of tumors by generating heat under near-infrared light irradiation through the photothermal effect.

[0005] The physicochemical properties of gold nanomaterials are closely related to their morphology. In the past decade or so, the morphology regulation of gold nanomaterials has mainly focused on nearly spherical shapes, triangular flakes, gold nanowires, gold nanorods, gold nanostars, and various polygonal gold nanoparticles. Their novel properties have potential application values in the fields of optics, medicine, catalysis, etc. Therefore, the morphology regulation of gold nanomaterials has attracted extensive attention from relevant scholars. They provide new possibilities for basic research and technological applications, while gold nanoparticles with a hollow network structure have not been reported yet. Summary of the Invention

[0006] The first object of the present invention is to provide a preparation method for hollow network gold nanoparticles. Through this method, the present invention synthesizes a novel-shaped hollow network gold nanoparticle for the first time, providing new possibilities for the basic research and technological applications of gold nanomaterials.

[0007] The second object of the present invention is to provide a hollow network gold nanoparticle.

[0008] The third object of the present invention is to provide an application of the hollow network gold nanoparticle.

[0009] To achieve the above objects, the present invention adopts the following technical solutions:

[0010] In the first aspect, the present invention provides a preparation method for hollow network gold nanoparticles, including the following steps:

[0011] Add polyvinylpyrrolidone to the gold source solution and disperse it by ultrasonic wave; add isooctanol, and then dropwise add an alkali solution under stirring conditions, mix evenly, and carry out a hydrothermal reaction.

[0012] Among them, first add polyvinylpyrrolidone to the gold source solution. There is a certain interaction between polyvinylpyrrolidone and gold ions, and the ultrasonic dispersion condition can assist the interaction force between polyvinylpyrrolidone and gold ions to be more uniform; then add the reducing agent isooctanol, and dropwise add the alkali solution under stirring conditions. Among them, the type of reducing agent combined with the dropwise addition of the alkali solution can adjust the speed of the reduction reaction, thereby regulating the morphology of the gold nanoparticles; finally, carry out a hydrothermal reaction to obtain hollow network gold nanoparticles.

[0013] Further, in the above method, the ratio of the gold source solution, polyvinylpyrrolidone, isooctanol, and alkali solution is 5 mL: 0.5 g - 2 g: 5 mL - 20 mL: 5 mL - 15 mL;

[0014] The concentration of the gold source solution is 100 mmol / L - 120 mmol / L; the concentration of the alkali solution is 2 mol / L. Among them, the ratio of each raw material within this range can better regulate the morphology of the gold nanoparticles.

[0015] The molecular weight of the polyvinylpyrrolidone is 10,000 - 70,000. Among them, when the molecular weight of the polyvinylpyrrolidone is within this range, the morphology of the gold nanoparticles can be better regulated. Too low or too high is not conducive to the formation of hollow network-shaped gold nanoparticles with regular morphology.

[0016] The time of ultrasonic dispersion is 20 min - 40 min. Among them, within this range of ultrasonic time, the regulatory effect of polyvinylpyrrolidone on gold nanoparticles can be better exerted. Exemplarily, the centrifugal speed is 8000 r / min.

[0017] The gold source solution includes chloroauric acid solution and / or chloroaurate solution; preferably chloroaurate solution.

[0018] The alkali solution is an aqueous solution of potassium hydroxide or an aqueous solution of sodium hydroxide; preferably an aqueous solution of potassium hydroxide.

[0019] The conditions of the hydrothermal reaction are: the temperature of the hydrothermal reaction is 160°C - 180°C, and the time of the hydrothermal reaction is 24 h - 60 h. Exemplarily, the container used for the hydrothermal reaction is a hydrothermal reaction kettle.

[0020] The preparation method further includes post-treatment steps of cooling to room temperature, centrifuging, washing, and drying.

[0021] Exemplarily, the drying is freeze-drying; the freeze-drying is carried out at -50°C for 24 h - 36 h.

[0022] Exemplarily, the centrifugal speed is 8000 r / min, and the centrifugal time is 10 min - 15 min; the washing method is to wash twice with water and ethanol respectively, and then centrifuge to collect the precipitate at a speed of 8000 r / min for 10 min - 15 min.

[0023] In the second aspect, the present invention provides a hollow network-shaped gold nanoparticle.

[0024] Exemplarily, the particle size of the hollow network-shaped gold nanoparticle is about 3 - 5 μm.

[0025] In the third aspect, the present invention provides an application of a hollow network-shaped gold nanoparticle in the preparation of a product for tumor photothermal therapy.

[0026] Furthermore, the photothermal therapy is photothermal therapy in the second near-infrared region.

[0027] Exemplarily, in the product for tumor photothermal therapy, the concentration of the hollow network-shaped gold nanoparticle is at least 100 μg / mL; preferably at least 400 μg / mL.

[0028] It should also be noted that, unless otherwise specified, any range described in the present invention includes the end values and any numerical values between the end values, as well as any sub-ranges formed by the end values or any numerical values between the end values. In the present invention, the preparation methods are all conventional methods unless otherwise specified, and the raw materials used can be obtained from public commercial channels or prepared according to the existing technology unless otherwise specified. The percentages are all mass percentages unless otherwise specified, the solutions are all aqueous solutions unless otherwise specified, and the reagents are all of analytical purity unless otherwise specified.

[0029] Advantages of the present invention

[0030] 1) The preparation method of the hollow network gold nanoparticles provided by the present invention is simple and feasible, has low requirements for equipment, uses less organic solvents, and is environmentally friendly.

[0031] 2) The hollow network gold nanoparticles provided by the present invention have a unique structure, providing new possibilities for the basic research and technical applications of gold nanomaterials.

[0032] 3) The hollow network gold nanoparticles provided by the present invention have strong absorption in the second near-infrared region and can be used to prepare products for tumor photothermal therapy. Description of the drawings

[0033] Figure 1 The scanning electron microscope image of the hollow network gold nanoparticles prepared in Example 1 at a scale of 10 μm is shown.

[0034] Figure 2 The scanning electron microscope image of the hollow network gold nanoparticles prepared in Example 1 at a scale of 1 μm is shown.

[0035] Figure 3 The absorption spectrum of the hollow network gold nanoparticles prepared in Example 1 is shown.

[0036] Figure 4 The comparison diagram of the photothermal curves of the aqueous dispersions of the hollow network gold nanoparticles with different concentrations prepared in Example 1 and pure water is shown.

[0037] Figure 5 The scanning electron microscope image of the hollow network gold nanoparticles prepared in Example 2 is shown.

[0038] Figure 6 The scanning electron microscope image of the gold nanoparticles prepared in Comparative Example 1 is shown.

[0039] Figure 7 The absorption spectrum of the gold nanoparticles prepared in Comparative Example 1 is shown.

[0040] Figure 8 The scanning electron microscope image of the gold nanoparticles prepared in Comparative Example 2 is shown.

[0041] Figure 9 The absorption spectrum of the gold nanoparticles prepared in Comparative Example 2 is shown.

[0042] Figure 10 The scanning electron microscope image of the gold nanoparticles prepared in Comparative Example 3 is shown. Detailed implementation manners

[0043] The present invention will be specifically described below through examples. It is necessary to point out here that these examples are only used to further illustrate the present invention and should not be construed as limiting the protection scope of the present invention. Those skilled in the art can make some non-essential improvements and adjustments based on the above content of the invention. Without conflict, the examples in the present invention and the features in the examples can be combined with each other.

[0044] The raw materials used in the present invention can be obtained from public commercial channels or prepared according to the prior art without special instructions.

[0045] Example 1

[0046] A method for preparing hollow reticular gold nanoparticles specifically includes the following steps:

[0047] 1) Weigh 170 mg of chloroauric acid, add 5 mL of ultrapure water, and prepare a gold source solution with a concentration of 100 mmol / L. Then add 1 g of polyvinylpyrrolidone (molecular weight 10,000 - 70,000, K30), and disperse evenly by ultrasonic treatment for 30 min.

[0048] 2) Add 5 mL of isooctanol, and then transfer the reaction system to a round-bottom flask; weigh 1.12 g of potassium hydroxide, dissolve it in 10 mL of ultrapure water to prepare a 2 mol / L potassium hydroxide solution, and dropwise add the potassium hydroxide solution to the reaction system in the round-bottom flask under magnetic stirring.

[0049] 3) Transfer the reaction system in the round-bottom flask to a 25 mL hydrothermal autoclave, place the hydrothermal autoclave in a homogeneous reactor, and react at 180 °C for 60 h.

[0050] 4) After the reaction is completed, wait for the reaction system to cool to room temperature, then centrifuge it at a speed of 8000 r / min for 10 min, collect the precipitate, wash it twice with ultrapure water and ethanol respectively, and centrifuge it at a speed of 8000 r / min for 10 min after each washing. After washing, freeze-dry it at -50 °C for 24 h to obtain the product.

[0051] Related characterizations:

[0052] The hollow reticular gold nanoparticles prepared in this example were analyzed by scanning electron microscopy, and the results are as Figure 1 ,Figure 2 as shown

[0053] The hollow network gold nanoparticles prepared in this example were subjected to ultraviolet-visible spectroscopy analysis, and the results are as Figure 3 shown

[0054] The hollow network gold nanoparticles prepared in this example were dispersed in water, and aqueous dispersions of hollow network gold nanoparticles with concentrations of 100 μg / mL, 200 μg / mL, 300 μg / mL, and 400 μg / mL were respectively prepared. Taking pure water as a control, they were irradiated with a laser with a wavelength of 1064 nm and a power of 1 W / cm 2 for 600 s. The photothermal curves are as Figure 4 shown

[0055] From Figure 1 and Figure 2 it can be seen that the hollow network gold nanoparticles obtained in this example have an obvious hollow network structure, and their particle size is about 3 - 5 μm

[0056] From Figure 3 it can be seen that the hollow network gold nanoparticles prepared in this example have a characteristic absorption of hollow network gold nanoparticles at 525 nm, and also have a relatively wide absorption in the second near-infrared region of 1000 nm - 1200 nm

[0057] From Figure 4 it can be seen that under the irradiation of a 1064 nm laser, the temperature of the aqueous dispersion of hollow network gold nanoparticles increased significantly. The temperature of the 400 μg / mL group rose to about 42 °C. Therefore, the hollow network gold nanoparticles prepared in this example can be applied to photothermal therapy

[0058] Example 2

[0059] A preparation method of hollow network gold nanoparticles specifically includes the following steps

[0060] 1) Weigh 170 mg of chloroauric acid, add 5 mL of ultrapure water to prepare a 100 mmol / L gold source solution, and then add 0.5 g of polyvinylpyrrolidone (molecular weight 10000 - 70000, K30), and ultrasonically disperse for 30 min until uniform

[0061] 2) Add 5 mL of isooctanol, and transfer the reaction system to a round-bottom flask; weigh 1.12 g of potassium hydroxide, dissolve it in 10 mL of ultrapure water to prepare a 2 mol / L potassium hydroxide solution, and dropwise add the potassium hydroxide solution to the reaction system in the round-bottom flask under magnetic stirring

[0062] 3) Transfer the reaction system in the round-bottom flask to a 25 mL hydrothermal autoclave, place the hydrothermal autoclave in a homogeneous reactor, and react at 180 °C for 24 h

[0063] 4) After the reaction is completed, wait for the reaction system to cool to room temperature, then centrifuge it at a speed of 8000 r / min for 10 min, collect the precipitate, wash it twice with ultrapure water and ethanol respectively, and centrifuge it at a speed of 8000 r / min for 10 min after each washing. After the washing is completed, freeze-dry it at -50 °C for 24 h to obtain the product.

[0064] It can be seen from Figure 5 that the morphology of the hollow network gold nanoparticles prepared in this example is similar to that of Example 1.

[0065] Example 3

[0066] A method for preparing hollow network gold nanoparticles specifically includes the following steps:

[0067] 1) Weigh 170 mg of chloroauric acid, add 5 mL of ultrapure water to prepare a 100 mmol / L gold source solution, then add 1 g of polyvinylpyrrolidone (molecular weight 10000 - 70000, K30), and disperse it evenly by ultrasonic treatment for 30 min.

[0068] 2) Add 10 mL of isooctanol, and transfer the reaction system to a round-bottom flask; weigh 1.12 g of potassium hydroxide, dissolve it in 10 mL of ultrapure water to prepare a 2 mol / L potassium hydroxide solution, and dropwise add the potassium hydroxide solution to the reaction system in the round-bottom flask under magnetic stirring.

[0069] 3) Transfer the reaction system in the round-bottom flask to a 25 mL hydrothermal reactor, place the hydrothermal reactor in a homogeneous reactor, and react at 180 °C for 60 h.

[0070] 4) After the reaction is completed, wait for the reaction system to cool to room temperature, then centrifuge it at a speed of 8000 r / min for 10 min, collect the precipitate, wash it twice with ultrapure water and ethanol respectively, and centrifuge it at a speed of 8000 r / min for 10 min after each washing. After the washing is completed, freeze-dry it at -50 °C for 24 h to obtain the product.

[0071] The morphology of the hollow network gold nanoparticles prepared in this example is similar to that of Example 1.

[0072] Example 4

[0073] A method for preparing hollow network gold nanoparticles specifically includes the following steps:

[0074] 1) Weigh 170 mg of chloroauric acid, add 5 mL of ultrapure water to prepare a 100 mmol / L gold source solution, then add 1 g of polyvinylpyrrolidone (molecular weight 10000 - 70000, K30), and disperse it evenly by ultrasonic treatment for 30 min.

[0075] 2) Add 5 mL of isooctanol, and transfer the reaction system to a round-bottom flask; weigh 1.68 g of potassium hydroxide, dissolve it in 15 mL of ultrapure water to prepare a 2 mol / L potassium hydroxide solution, and dropwise add the potassium hydroxide solution to the reaction system in the round-bottom flask under magnetic stirring.

[0076] 3) Transfer the reaction system in the round-bottom flask to a 25 mL hydrothermal autoclave, place the hydrothermal autoclave in a homogeneous reactor, and react at 180 °C for 60 h.

[0077] 4) After the reaction is completed, wait for the reaction system to cool to room temperature, then centrifuge it at a speed of 8000 r / min for 10 min, collect the precipitate, wash it twice with ultrapure water and ethanol respectively, and centrifuge it at a speed of 8000 r / min for 10 min after each washing. After washing, freeze-dry it at -50 °C for 24 h to obtain the product.

[0078] The morphology of the hollow network gold nanoparticles prepared in this example is similar to that in Example 1.

[0079] Comparative Example 1

[0080] Same as Example 1, the only difference is that 5 mL of isooctanol is replaced with 5 mL of 1 mg / mL NaBH4 solution.

[0081] The gold nanoparticles prepared in this example were analyzed by scanning electron microscopy, and the results are as Figure 6 shown.

[0082] The gold nanoparticles prepared in this example were analyzed by ultraviolet-visible spectroscopy, and the results are as Figure 7 shown.

[0083] It can be seen from Figure 6 that the gold nanoparticles prepared in this example have an irregular morphology, and the hollow network structure cannot be observed.

[0084] It can be seen from Figure 7 that the gold nanoparticles prepared in this example have a strong absorption at 525 nm and almost no absorption peak in the near-infrared region greater than 700 nm. This result indicates that the gold nanoparticles prepared in this example have almost no absorption in the second near-infrared region.

[0085] Comparative Example 2

[0086] Same as Example 1, the only difference is that 1 g of polyvinylpyrrolidone (molecular weight 10000 - 70000, K30) is replaced with 1 g of polyvinylpyrrolidone (molecular weight 3500, K12).

[0087] The gold nanoparticles prepared in this example were analyzed by scanning electron microscopy, and the results are as Figure 7as shown

[0088] The prepared gold nanoparticles in this example were analyzed by ultraviolet-visible spectroscopy, and the results are as Figure 8 shown

[0089] It can be seen from Figure 8 that the morphology of the prepared gold nanoparticles in this example presents a relatively regular spherical shape, but the network structure cannot be observed

[0090] It can be seen from Figure 9 that the prepared gold nanoparticles in this example have a strong absorption at 525 nm and a very weak absorption in the second near-infrared region of 1000 nm - 1200 nm

[0091] Comparative Example 3

[0092] Same as Example 1, the difference is only that 1 g of polyvinylpyrrolidone (molecular weight 10,000 - 70,000, K30) is replaced by 1 g of cetyltrimethylammonium bromide (CTAB)

[0093] The prepared gold nanoparticles in this example were analyzed by scanning electron microscopy, and the results are as Figure 10 shown

[0094] It can be seen from Figure 10 that the morphology of the prepared gold nanoparticles in this example presents a spherical shape, but the network structure cannot be observed

[0095] Obviously, the above embodiments of the present invention are only examples for clearly illustrating the present invention, rather than limitations on the implementation manners of the present invention. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is impossible to list all the implementation manners here. Any obvious changes or modifications derived from the technical solutions of the present invention still fall within the protection scope of the present invention

Claims

1. A preparation method of hollow network gold nanoparticles, characterized in that, It includes the following steps: Add polyvinylpyrrolidone to the gold source solution, add isooctanol after ultrasonic dispersion, and then dropwise add the alkali solution under stirring conditions, mix evenly, and carry out hydrothermal reaction; The ratio of the gold source solution, polyvinylpyrrolidone, isooctanol and alkali solution is 5 mL: 0.5 g - 2 g: 5 mL - 20 mL: 5 mL - 15 mL; The concentration of the gold source solution is 100 mmol / L - 120 mmol / L; the concentration of the alkali solution is 2 mol / L; The molecular weight of the polyvinylpyrrolidone is 10,000 - 70,000; The conditions of the hydrothermal reaction are: the temperature of the hydrothermal reaction is 160 °C - 180 °C, and the time of the hydrothermal reaction is 24 h - 60 h.

2. The preparation method according to claim 1, wherein The time of ultrasonic dispersion is 20 min - 40 min.

3. The preparation method according to claim 1, characterized in that, The gold source solution includes chloroauric acid solution and / or chloroaurate solution.

4. The preparation method according to claim 1, characterized in that, The alkali solution is an aqueous solution of potassium hydroxide or an aqueous solution of sodium hydroxide.

5. The preparation method according to claim 1, wherein It also includes post-treatment steps of cooling, centrifuging, washing and drying.

6. A hollow reticular gold nanoparticle prepared by the preparation method according to any one of claims 1 - 5.

7. Use of the hollow reticular gold nanoparticle according to claim 6 in the preparation of a product for tumor photothermal therapy.

8. The application according to claim 7, characterized in that, The photothermal therapy is photothermal therapy in the second near-infrared region.

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