Preparation method and application of Prussian blue nanomaterial with NIR-Ⅱ absorption characteristics

Abstract

The present invention aims to provide a preparation method and application of a Prussian blue nanomaterial with NIR-II absorption characteristics, belonging to the technical field of Prussian blue nanomaterials. The method comprises reacting melanin (water-soluble) and ferrocyanide salt in a dilute acid solution, adding polyvinyl pyrrolidone, and centrifuging and drying. The prepared MPB has efficient light absorption characteristics in the 900-1200 nm region and can be effectively used for NIR-II PA / PTT.

Description

Technical Field

[0001] The invention belongs to the technical field of Prussian blue nanomaterials, and particularly relates to a preparation method and application of a Prussian blue nanomaterial with NIR-II absorption characteristics. Background Art

[0002] Prussian blue (PB, Fe₄[Fe(CN)₆]) is a US Food and Drug Administration (FDA)-approved antidote commonly used in the clinical treatment of poisoning caused by radioactive elements such as thallium. Due to its tunable size and excellent properties, PB plays an important role in diagnostic and therapeutic applications such as drug delivery, photothermal therapy, and molecular imaging.

[0003] Photoacoustic imaging (PA) is an emerging noninvasive diagnostic technique that combines the advantages of optical and ultrasound imaging, offering excellent sensitivity, high resolution, and real-time imaging capabilities. However, its tissue penetration depth and spatial resolution are limited in the visible and first near-infrared windows (NIR-I, 700-900 nm). In contrast, photoacoustic contrast agents in the second near-infrared window (NIR-II, 900-1700 nm) offer enhanced penetration, higher signal-to-noise ratio, and improved imaging quality, providing more comprehensive and in-depth physiological and pathological information in vivo.

[0004] Although PB has considerable absorbance in the near-infrared (NIR) and is often used as a PA contrast agent and photothermal conversion agent for diagnosis and photothermal therapy (PTT), its maximum NIR absorption peak is usually located in the range of 690-720 nm, and its absorption characteristics in the NIR-II region are weak and have little to do with changes in its basic physical properties such as size, structure, and morphology. Currently, there is still a lack of effective preparation methods for the NIR-II absorption characteristics of PB. In addition, in the only reports on PB with NIR-II absorption characteristics, the preparation methods of these PBs are complex and their biocompatibility needs to be improved. Therefore, adjusting the maximum absorbance of PB in the NIR-II region and further enhancing its PA and PTT capabilities to meet the needs of precise and efficient diagnosis and treatment are of great significance and challenges. Summary of the Invention

[0005] The purpose of the present invention is to provide a preparation method and application of Prussian blue nanomaterials with NIR-Ⅱ absorption characteristics. This method can be used to simply and mass-produce functionalized Prussian blue nanomaterials (MPB). The MPB prepared by this method exhibits excellent absorption characteristics in the NIR-Ⅱ region, significantly enhances PA performance and photothermal conversion efficiency, and can be effectively used in NIR-Ⅱ PA / PTT.

[0006] The present invention adopts the following technical solutions:

[0007] A method for preparing a Prussian blue nanomaterial having NIR-II absorption characteristics comprises the following steps:

[0008] S1. Dissolve melanin (water-soluble) and ferricyanide salt in a dilute acid solution, and disperse them uniformly by ultrasonication to prepare a homogenized solution;

[0009] S2. The homogenized solution prepared in step S1 was transferred to a beaker and placed in a thermostatic stirrer with uniform stirring at a speed of 500-1200 r / min. Polyvinyl pyrrolidone was then added stepwise and stirred at room temperature for 1-4 h until the solution became transparent to obtain a homogenized mixed solution.

[0010] S3. Transfer the homogenized mixed solution obtained in S2 to a round-bottom flask, heat it to 60-90°C, react for 8-24 hours, and then centrifuge the obtained solution at a speed of 3500-12000 r / min. Finally, dry it to obtain the functionalized Prussian blue nanomaterial MPB with NIR-Ⅱ absorption characteristics.

[0011] Furthermore, the ferrocyanide salt in step S1 includes any one of potassium ferrocyanide, potassium ferrocyanide, sodium ferrocyanide, and sodium ferrocyanide.

[0012] Furthermore, the pH of the dilute acid solution in step S1 is 6-8, and includes any one of hydrochloric acid, sulfuric acid, acetic acid, and citric acid.

[0013] Furthermore, the mass volume ratio of the melanin (water-soluble), ferricyanide salt and dilute acid solution in step S1 is (10 mg 200 mg): (10 mg 200 mg): (3 mL-100 mL);

[0014] The frequency of the ultrasonic dispersion is 25 kHz-80 kHz, and the time of the ultrasonic dispersion is 10-60 min.

[0015] Furthermore, the mass of the polyvinyl pyrrolidone in step S2 is 0.2-0.6 g.

[0016] A functionalized Prussian blue nanomaterial with near-infrared second region light absorption properties is applied to NIR-ⅡPA / PTT.

[0017] The beneficial effects of the present invention are as follows:

[0018] 1. This invention provides a functionalized Prussian blue nanomaterial (MPB) with near-infrared II light absorption properties. The material is prepared by reacting water-soluble melanin and ferrocyanide salt in a dilute acid solution, adding polyvinylpyrrolidone, and centrifuging and drying. The prepared MPB exhibits efficient light absorption in the 900-1200 nm region and is suitable for use in NIR-II PA / PTT.

[0019] 2. The preparation method of the present invention is simple and can be prepared in large quantities.

[0020] 3. The MPB composition of the present invention is simple and safe, and has excellent biocompatibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is a transmission electron microscope (TEM) image of the MPB synthesized in Example 1 of the present invention.

[0022] Figure 2 This is the XRD spectrum of MPB synthesized in Example 1 of the present invention.

[0023] Figure 3 This is the UV absorption spectrum of MPB synthesized in Example 1 of the present invention.

[0024] Figure 4 This is the oxygen release spectrum of MPB synthesized in Example 1 of the present invention.

[0025] Figure 5 This is the temperature change curve of MPB with different concentrations synthesized in Example 1 of the present invention under laser irradiation over time.

[0026] Figure 6 The photothermal performance spectrum of MPB synthesized in Example 1 of the present invention under laser irradiation at different laser power densities

[0027] Figure 7 This is the photothermal cycle spectrum of MPB synthesized in Example 1 of the present invention.

[0028] Figure 8 This is a photothermal conversion efficiency spectrum calculated according to the photothermal cooling curve of the MPB synthesized in Example 1 of the present invention.

[0029] Figure 9 These are NIR-II 3D PA images of MPB with different concentrations synthesized in Example 1 of the present invention.

[0030] Figure 10 These are NIR-II 3DPA images of the lesion site at different times after the MPB synthesized in Example 1 of the present invention was injected into the tail vein. DETAILED DESCRIPTION

[0031] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0032] Example 1

[0033] The preparation of functionalized Prussian blue nanomaterials with NIR-Ⅱ absorption comprises the following steps:

[0034] S1. Dissolve melanin (water-soluble) and potassium ferrocyanide in a dilute acid solution at a mass volume ratio of 100 mg melanin (water-soluble), 100 mg potassium ferrocyanide, and dilute acid solution to obtain a homogenized solution by ultrasonic dispersion at a frequency of 60 kHz for 30 minutes.

[0035] S2. The homogenized solution obtained in step S1 was transferred to a beaker, and then placed in a thermostatic stirrer with uniform stirring at a speed of 600 r / min. Then, 0.4 g of polyvinyl pyrrolidone was added stepwise and stirred at high speed at room temperature for 3 h until the solution became transparent to obtain a homogenized mixed solution.

[0036] S3. The homogenized mixed solution prepared in S2 was transferred to a round-bottom flask, heated to 70 °C, and reacted for 12 h. The obtained solution was then centrifuged at a speed of 8000 r / min and finally dried to obtain functionalized Prussian blue nanomaterial (MPB) with NIR-Ⅱ absorption characteristics.

[0037] Figure 1 This is a TEM image of the MPB synthesized in Example 1. As can be seen from the figure, the synthesized nanomaterial particles are uniform in size, presenting a square block structure with a diameter of about 200 nm.

[0038] Figure 2 This is the XRD pattern of MPB synthesized in Example 1. As can be seen from the figure, the diffraction peaks at 17.4°, 24.6°, 35.2° and 39.4° correspond to the (200), (220), (400) and (420) crystal planes, respectively, indicating that MPB is a PB analogue.

[0039] Figure 3 This is the UV absorption spectrum of MPB synthesized in Example 1. Compared with PB, MPB exhibits obvious NIR-II light absorption characteristics in the 900-1200 nm region and can be used for NIR-II PA / PTT.

[0040] Figure 4This is the oxygen release spectrum of MPB synthesized in Example 1. As can be seen from the figure, compared with PB and water, MPB has the strongest oxygen production capacity.

[0041] Figure 5 The temperature change curves of MPB with different concentrations synthesized in Example 1 under laser irradiation over time are shown in the figure. As can be seen from the figure, MPB with different solubilities all show a rapid temperature increase under laser irradiation, while the temperature of pure water remains almost unchanged.

[0042] Figure 6 The photothermal performance spectra of the MPB synthesized in Example 1 under different laser power densities are shown. As can be seen from the figure, MPB exhibits rapid temperature rise when irradiated by lasers at different powers, and the higher the power, the higher the temperature rise rate and amplitude.

[0043] Figure 7 This is the photothermal cycle spectrum of the MPB synthesized in Example 1. As can be seen from the figure, MPB can also maintain good photothermal stability even in a long cycle time.

[0044] Figure 8 The photothermal conversion efficiency spectrum is calculated based on the photothermal cooling curve of the MPB synthesized in Example 1. As can be seen from the figure, MPB has a high photothermal conversion efficiency.

[0045] Figure 9 These are NIR-II 3D PA images of MPB at different concentrations synthesized in Example 1. As can be seen from the figure, the photoacoustic signal of MPB is linearly correlated with its concentration, and the photoacoustic signal intensity increases with increasing solubility.

[0046] Figure 10 These are NIR-II 3D PA images of lesions at different times after tail vein injection of the MPB synthesized in Example 1. As shown, after MPB solution was injected into myeloma-bearing nude mice via the tail vein, PA signals were collected from the lesion tissue. The 3D PA signal at the lesion site showed a time-dependent increase, reaching a peak 8 hours after injection. Compared to pre-injection levels, the signal increased several-fold, demonstrating excellent lesion-specific NIR-II 3D PA imaging capabilities. Furthermore, in vivo experiments demonstrated the excellent biosafety of MPB.

[0047] Example 2

[0048] The preparation of functionalized Prussian blue nanomaterials with NIR-Ⅱ absorption comprises the following steps:

[0049] S1. Dissolve melanin (water-soluble) and sodium ferrocyanide in a dilute acid solution at a mass volume ratio of 100 mg melanin (water-soluble), 100 mg sodium ferrocyanide, and 40 mL dilute acid solution. Ultrasonic dispersion is performed at a frequency of 60 kHz for 30 minutes to obtain a homogenized solution.

[0050] S2. The homogenized solution obtained in step S1 was transferred to a beaker, and then placed in a thermostatic stirrer with uniform stirring at a speed of 600 r / min. 0.3 g of polyvinyl pyrrolidone was then added stepwise and stirred at high speed at room temperature for 4 h until the solution became transparent to obtain a homogenized mixed solution.

[0051] S3. Transfer the homogenized mixed solution prepared in S2 to a round-bottom flask, heat it to 75 °C, react for 12 h, then centrifuge the obtained solution at a speed of 8000 r / min, and finally dry it to obtain functionalized Prussian blue nanomaterial (MPB) with NIR-Ⅱ absorption characteristics.

[0052] Example 3

[0053] The preparation of functionalized Prussian blue nanomaterials with NIR-Ⅱ absorption comprises the following steps:

[0054] S1. Dissolve melanin (water-soluble) and potassium ferrocyanide in a dilute acid solution at a mass volume ratio of 100 mg melanin (water-soluble), 100 mg potassium ferrocyanide, and dilute acid solution to 40 mL. Ultrasonic dispersion is performed at a frequency of 70 kHz for 30 minutes to obtain a homogenized solution.

[0055] S2. The homogenized solution obtained in step S1 was transferred to a beaker, and then placed in a thermostatic stirrer with uniform stirring at a speed of 600 r / min. Then, 0.3 g of polyvinyl pyrrolidone was added stepwise, and stirred at high speed at room temperature for 3 h until the solution became transparent to obtain a homogenized mixed solution.

[0056] S3. The homogenized mixed solution prepared in S2 was transferred to a round-bottom flask, heated to 70 °C, and reacted for 12 h. The obtained solution was then centrifuged at a speed of 8000 r / min and finally dried to obtain functionalized Prussian blue nanomaterial (MPB) with NIR-Ⅱ absorption characteristics.

[0057] Example 4

[0058] The preparation of functionalized Prussian blue nanomaterials with NIR-Ⅱ absorption comprises the following steps:

[0059] S1. Dissolve melanin (water-soluble) and potassium ferrocyanide in a dilute acid solution at a mass volume ratio of 100 mg:100 mg:40 mL of the dilute acid solution. Ultrasonic dispersion is performed at a frequency of 60 kHz for 30 min to obtain a homogenized solution.

[0060] S2. The homogenized solution obtained in step S1 was transferred to a beaker, and then placed in a thermostatic stirrer with uniform stirring at a speed of 600 r / min. Then, 0.3 g of polyvinyl pyrrolidone was added stepwise, and stirred at high speed at room temperature for 3 h until the solution became transparent to obtain a homogenized mixed solution.

[0061] S3. The homogenized mixed solution prepared in S2 was transferred to a round-bottom flask, heated to 70 °C, and reacted for 12 h. The obtained solution was then centrifuged at a speed of 8000 r / min and finally dried to obtain functionalized Prussian blue nanomaterial (MPB) with NIR-Ⅱ absorption characteristics.

[0062] Example 5

[0063] The preparation of functionalized Prussian blue nanomaterials with NIR-Ⅱ absorption comprises the following steps:

[0064] S1. Dissolve melanin (water-soluble) and sodium ferrocyanide in a dilute acid solution at a mass volume ratio of 100 mg melanin (water-soluble), 100 mg sodium ferrocyanide, and 40 mL dilute acid solution. Ultrasonic dispersion is performed at a frequency of 60 kHz for 30 min to obtain a homogenized solution.

[0065] S2. The homogenized solution obtained in step S1 was transferred to a beaker, and then placed in a thermostatic stirrer with uniform stirring at a speed of 600 r / min. Then, 0.3 g of polyvinyl pyrrolidone was added stepwise, and stirred at high speed at room temperature for 3 h until the solution became transparent to obtain a homogenized mixed solution.

[0066] S3. Transfer the homogenized mixed solution prepared in S2 to a round-bottom flask, heat it to 70 °C, react for 14 h, then centrifuge the obtained solution at a speed of 8000 r / min, and finally dry it to obtain functionalized Prussian blue nanomaterial (MPB) with NIR-Ⅱ absorption characteristics.

[0067] Example 6

[0068] The preparation of functionalized Prussian blue nanomaterials with NIR-Ⅱ absorption comprises the following steps:

[0069] S1. Dissolve melanin (water-soluble) and potassium ferrocyanide in a dilute acid solution at a mass volume ratio of 100 mg melanin (water-soluble), 100 mg potassium ferrocyanide, and dilute acid solution to obtain a homogenized solution by ultrasonic dispersion at a frequency of 60 kHz for 30 minutes.

[0070] S2. The homogenized solution obtained in step S1 was transferred to a beaker, and then placed in a thermostatic stirrer with uniform stirring at a speed of 600 r / min. Then, 0.3 g of polyvinyl pyrrolidone was added stepwise, and stirred at high speed at room temperature for 3 h until the solution became transparent to obtain a homogenized mixed solution.

[0071] S3. The homogenized mixed solution prepared in S2 was transferred to a round-bottom flask, heated to 70 °C, and reacted for 16 h. The obtained solution was then centrifuged at 8000 r / min and dried to obtain functionalized Prussian blue nanomaterial (MPB) with NIR-Ⅱ absorption characteristics.

[0072] Example 7

[0073] The preparation of functionalized Prussian blue nanomaterials with NIR-Ⅱ absorption comprises the following steps:

[0074] S1. Dissolve melanin (water-soluble) and sodium ferrocyanide in a dilute acid solution at a mass volume ratio of 100 mg melanin (water-soluble), 100 mg sodium ferrocyanide, and 40 mL dilute acid solution. Ultrasonic dispersion is performed at a frequency of 70 kHz for 40 min to obtain a homogenized solution.

[0075] S2. The homogenized solution obtained in step S1 was transferred to a beaker, and then placed in a thermostatic stirrer with uniform stirring at a speed of 800 r / min. Then, 0.3 g of polyvinyl pyrrolidone was added stepwise, and stirred at high speed at room temperature for 3 h until the solution became transparent to obtain a homogenized mixed solution.

[0076] S3. Transfer the homogenized mixed solution prepared in S2 to a round-bottom flask, heat it to 70 °C, react for 10 h, then centrifuge the obtained solution at a speed of 8000 r / min, and finally dry it to obtain functionalized Prussian blue nanomaterial (MPB) with NIR-Ⅱ absorption characteristics.

Claims

1. A method for preparing a Prussian blue nanomaterial with NIR-II absorption characteristics, characterized by: The steps include: S1, dissolving water-soluble melanin and ferricyanide salt in a dilute acid solution, and uniformly dispersing them by ultrasonication to prepare a homogenized solution; S2. The homogenized solution prepared in step S1 was transferred to a beaker and placed in a thermostatic stirrer with uniform stirring at a speed of 500-1200 r / min. Polyvinyl pyrrolidone was then added stepwise and stirred at room temperature for 1-4 h until the solution became transparent to obtain a homogenized mixed solution. S3. Transfer the homogenized mixed solution obtained in S2 to a round-bottom flask, heat it to 60-90°C, react for 8-24 hours, and then centrifuge the obtained solution at a speed of 3500-12000 r / min. Finally, dry it to obtain the functionalized Prussian blue nanomaterial MPB with NIR-Ⅱ absorption characteristics.

2. The method for preparing a Prussian blue nanomaterial having NIR-II absorption characteristics according to claim 1, characterized in that: The ferrocyanide salt in step S1 includes any one of potassium ferrocyanide, potassium ferrocyanide, sodium ferrocyanide, and sodium ferrocyanide.

3. The method for preparing a Prussian blue nanomaterial having NIR-II absorption characteristics according to claim 1, characterized in that: The dilute acid solution in step S1 includes any one of hydrochloric acid, sulfuric acid, acetic acid, and citric acid.

4. The method for preparing a Prussian blue nanomaterial having NIR-II absorption characteristics according to claim 1, characterized in that: The mass volume ratio of the water-soluble melanin, ferricyanide salt and dilute acid solution in step S1 is 10 mg-200 mg: 10 mg-200 mg: 3 mL-100 mL; The frequency of the ultrasonic dispersion is 25 kHz-80 kHz, and the time of the ultrasonic dispersion is 10-60 min.

5. The method for preparing a Prussian blue nanomaterial having NIR-II absorption characteristics according to claim 1, characterized in that: The mass of the polyvinyl pyrrolidone in step S2 is 0.2-0.6 g.

6. Use of a functionalized Prussian blue nanomaterial having near-infrared second region light absorption characteristics prepared by the method of claim 1 in the preparation of NIR-II PA / PTT materials.

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