Biocompatible elemental selenium nanotubes and methods of making the same

Abstract

The application discloses a kind of biocompatibility elemental selenium nanotubes and preparation method thereof, belong to the field of nano elemental selenium synthesis, homogeneous mixture is obtained by mixing cerium sulfate solution, sodium hydroxide solution and selenium hydrazine dispersion liquid, the concentration of cerium sulfate solution is 2~4mmol / L, the concentration of selenium powder in selenium hydrazine dispersion liquid is 300~380mmol / L, to obtain mixed system, the mixed system is carried out hydrothermal reaction at 60~90 DEG C, to obtain reaction liquid, the product in reaction liquid is separated and dried, and the cell experiment result proves that biocompatibility elemental selenium nanotube is obtained.The application solves the lack of controllable and stable synthesis problem existing in the synthesis process of the prior art elemental selenium nanotube, and facilitates the application in the medical field as a drug carrier in the later period.

Description

Technical Field

[0001] This invention belongs to the field of nano-selenium synthesis, specifically a biocompatible elemental selenium nanotube and its preparation method. Background Technology

[0002] Selenium can enter cells to form selenoproteins, scavenging intracellular free radicals and thus exerting antioxidant and biological functions. Nano-selenium possesses properties such as high specific surface area, high activity, and ease of surface functionalization, showing broad application prospects in the biomedical field. Compared to traditional inorganic or organic selenium compounds, elemental selenium exhibits lower biotoxicity, making its controllable synthesis at the nanoscale crucial for promoting its application in biomedicine.

[0003] Currently, numerous applications of elemental selenium / seleno-loaded nanoparticles in the biomedical field have been reported. For example, in anti-tumor therapy, elemental selenium nanoparticles not only exert direct anti-cancer effects by inducing oxidative stress death in cancer cells and regulating key signaling pathways, but also serve as efficient carriers for targeted delivery of chemotherapeutic drugs or gene therapy agents, significantly enhancing the sensitization of radiotherapy and chemotherapy. In terms of antioxidant defense, selenium ions enter cells to promote the formation of selenoproteins, reducing inflammatory responses by scavenging excess free radicals, thus providing protection against neurodegenerative diseases, diabetic complications, and organ damage. Simultaneously, selenium nanoparticles can disrupt pathogen structures and induce reactive oxygen species bursts, achieving highly efficient antibacterial and biofilm clearance capabilities, providing new strategies for combating drug-resistant bacterial infections and promoting the healing of infected wounds. Although elemental selenium nanoparticles still face challenges in targeting efficiency, long-term in vivo behavior assessment, and large-scale controllable synthesis, their potential for integrated diagnosis and treatment is bringing breakthrough solutions to key medical areas such as precision oncology, anti-infection, and tissue repair, and their prospects for clinical translation are attracting considerable attention.

[0004] Existing methods for preparing elemental selenium nanoparticles mainly include chemical reduction, biosynthesis, laser ablation, radiation synthesis, and template methods. However, these processes all suffer from stringent synthesis conditions and / or difficulties in morphology control. Furthermore, although some literature reports the synthesis of elemental selenium via ascorbic acid reduction, microbial-mediated biosynthesis, and polysaccharide template-assisted synthesis, the products are primarily nanoparticles, but these methods suffer from residual toxicity of reducing agents, poor morphology and size control, and low process reproducibility. How to synthesize elemental selenium nanotubes is crucial for their application as drug carriers in the medical field. For example, Chinese invention patent application number 03150805.7 discloses a method for preparing elemental selenium nanotubes, specifically involving placing elemental selenium powder in an autoclave, adding water, alcohol, ammonia, and hydrazine, reacting at 100–500°C for 1–200 h, sonicating for 1–10 h, centrifuging, and drying. This method utilizes the reaction of ammonia and hydrazine to form stable hydrazine hydrate, which dissolves selenium powder. Elemental selenium nanotubes are then obtained under hydrothermal conditions. However, the high temperature of the reaction system and the easy volatilization of ammonia lead to instability in the content of the hydrazine hydrate formed from the ammonia and hydrazine. Consequently, the diameter, length distribution, and morphology of the resulting selenium nanotubes are difficult to control, resulting in poor process stability and reproducibility. The diameter of the obtained selenium nanotubes is approximately 500 nanometers, making them unsuitable as biocompatible drug carriers. Therefore, to date, a controllable and stable synthesis process for elemental selenium nanotubes is lacking, which would enable the obtained nanotubes to possess biocompatibility and be used as drug carriers in the medical field. Summary of the Invention

[0005] To address the problems existing in the prior art, this invention provides a biocompatible elemental selenium nanotube and its preparation method. This method controls the concentration of cerium sulfate solution, the concentration of selenium powder in the selenium hydrazine hydrate dispersion, and the temperature of the hydrothermal reaction. The selenium powder undergoes reduction-oxidation self-assembly to form high-purity and uniform elemental selenium nanotubes, thus solving the problem of lack of controllable and stable synthesis in existing elemental selenium nanotube synthesis processes. The obtained elemental selenium nanotubes are biocompatible, making them convenient for later use as drug carriers in the medical field.

[0006] This invention is achieved through the following technical solution:

[0007] A method for preparing biocompatible elemental selenium nanotubes specifically includes the following steps:

[0008] Step 1: Mix the cerium sulfate solution, sodium hydroxide solution and selenium hydrazine hydrate dispersion evenly, wherein the concentration of the cerium sulfate solution is 2~4 mmol / L and the concentration of selenium powder in the selenium hydrazine hydrate dispersion is 300~380 mmol / L to obtain a mixed system.

[0009] Step 2: The mixture is subjected to a hydrothermal reaction at 60~90℃ for 2~12 hours to obtain a reaction solution;

[0010] Step 3: After separating and drying the products in the reaction solution, biocompatible elemental selenium nanotubes are obtained.

[0011] Preferably, in step 1, the concentration of the sodium hydroxide solution is 3~5 mmol / L.

[0012] Further, in step 1, the cerium sulfate solution, sodium hydroxide solution and selenium hydrazine hydrate dispersion are mixed evenly in a volume ratio of 2.5:1:1 to obtain a mixed system.

[0013] Preferably, in step 1, the solvent for the cerium sulfate solution is anhydrous ethanol.

[0014] Preferably, in step 1, the selenium hydrated hydrazine dispersion is obtained by adding selenium powder to a hydrazine hydrate solution with a mass percentage of 70%-80% and dispersing it evenly.

[0015] Preferably, in step 3, the reaction solution is centrifuged and washed with deionized water to obtain a black powder, which is then dried to obtain biocompatible elemental selenium nanotubes.

[0016] Furthermore, the centrifugal washing is performed 3 to 5 times, each time at 7800 to 9500 rpm for 1 to 6 minutes, and the black powder is dried at 60 to 90°C for 1 to 12 hours.

[0017] A biocompatible elemental selenium nanotube obtained by any of the above-mentioned methods.

[0018] Compared with the prior art, the present invention has the following beneficial technical effects:

[0019] This invention discloses a method for preparing biocompatible elemental selenium nanotubes. By controlling the concentration of cerium sulfate solution, the concentration of selenium powder in a hydrazine hydrate dispersion, and the temperature of the hydrothermal reaction, selenium powder undergoes a reduction-oxidation process to self-assemble into high-purity and homogeneous elemental selenium nanotubes. Hydrazine hydrate, possessing high chemical stability, acts as a reducing agent to reduce Se powder to hydrogen selenide, causing the selenium powder to dissolve. The electron distribution of cerium is [Xe] 4f²6s², which facilitates the conversion of cerium ions in cerium sulfate between the +3 and +4 valence states. Cerium sulfate can provide Ce in the mixed system. +3 and Ce +4 Ce during hydrothermal process 3+ It can work synergistically with hydrazine hydrate to further reduce Se powder to hydrogen selenide, Ce 4+Selenium is oxidized to elemental selenium. In the alkaline environment formed by sodium hydroxide, elemental selenium nuclei gradually self-assemble into nanotube structures. Elemental selenium nanotubes have a high specific surface area, making them effective drug carriers. Furthermore, they can slowly release selenium ions under the influence of body fluids, achieving controllable local selenium ion concentration and exhibiting certain biocompatibility. This provides a foundation for expanding the application of selenium in the biomedical field.

[0020] Furthermore, by adjusting the sodium hydroxide solution concentration to 3-5 mmol / L, within a hydrothermal temperature range of 60-90℃ and a reaction time of 2-12 h, the growth rate of elemental selenium nucleation increased with increasing hydrothermal time and sodium hydroxide concentration, and the diameter of elemental selenium nanotubes increased to approximately 150 nm-400 nm, with an average length of 7.5-45 μm. Cell experiments demonstrated that the elemental selenium nanotubes with this morphology have good biocompatibility. Attached Figure Description

[0021] Figure 1 This is a SEM image of the biocompatible elemental selenium nanotubes obtained in Example 1 of the present invention.

[0022] Figure 2 This is a SEM image of the biocompatible elemental selenium nanotubes obtained in Example 2 of the present invention.

[0023] Figure 3 This is a SEM image of the biocompatible elemental selenium nanotubes obtained in Example 3 of the present invention.

[0024] Figure 4 This is a SEM image of the biocompatible elemental selenium nanotubes obtained in Example 4 of the present invention.

[0025] Figure 5 This is a SEM image of the biocompatible elemental selenium nanotubes obtained in Example 5 of the present invention.

[0026] Figure 6 This is a SEM image of the biocompatible elemental selenium nanotubes obtained in Example 6 of the present invention.

[0027] Figure 7 For the present invention Figure 1 The image shows the staining of live cells obtained from cell experiments using biocompatible elemental selenium nanotubes.

[0028] Figure 8 For the present invention Figure 1 Image of dead cells stained with biocompatible elemental selenium nanotubes in cell experiments. Detailed Implementation

[0029] The present invention will be further described in detail below with reference to specific embodiments. These descriptions are for explanation purposes only and are not intended to limit the scope of the invention.

[0030] This invention discloses a method for preparing biocompatible elemental selenium nanotubes, specifically comprising the following steps:

[0031] Step 1: Using anhydrous ethanol as solvent and cerium sulfate as solute, the chemical formula of cerium sulfate is Ce(SO4)2·4H2O. Prepare a cerium sulfate ethanol solution with a concentration of 2~4 mmol / L, denoted as solution A.

[0032] Step 2: Prepare a sodium hydroxide solution with a concentration of 3~5 mmol / L using deionized water as solvent and sodium hydroxide as solute, and denote it as solution B;

[0033] Step 3: Add selenium powder to a hydrazine hydrate solution with a mass percentage of 70%~80%, control the concentration of selenium powder to be 300~380 mmol / L, and mechanically stir to fully disperse the selenium powder to obtain a selenium dispersion.

[0034] Step 4: Mix solution A, solution B and selenium dispersion in a volume ratio of 12.5:5:5 to obtain a mixed system;

[0035] Step 5: Place 22.5 ml of the mixture into a 50 ml hydrothermal reactor and hydrothermally react at 60-90℃ for 2-12 hours;

[0036] Step 6: After the reaction is complete, the reaction solution is centrifuged and washed 3-5 times with 30-50 ml of deionized water at 7800-9500 rpm for 1-6 min each time. Finally, the black powder is dried in an oven at 60-90℃ for 1-12 h to obtain elemental selenium nanotubes.

[0037] This invention controls the concentration of cerium sulfate solution and the concentration of selenium powder in the hydrazine hydrate dispersion, as well as the temperature of the hydrothermal reaction, to enable the selenium powder to form high-purity and uniform elemental selenium nanotubes through a reduction-oxidation self-assembly process. Hydrazine hydrate, with its high chemical stability, acts as a reducing agent to reduce Se powder to hydrogen selenide, causing the selenium powder to dissolve. The electron distribution of cerium is [Xe] 4f²6s², facilitating the conversion of cerium ions between +3 and +4 valence states in cerium sulfate solution. Cerium sulfate can provide Ce in the mixed system. +3 and Ce +4 Ce during hydrothermal process 3+ It can work synergistically with hydrazine hydrate to further reduce Se powder to hydrogen selenide, Ce 4+ When selenide is oxidized to elemental selenium, the elemental selenium gradually self-assembles into a nanotube structure in the alkaline environment formed by sodium hydroxide.

[0038] Example 1

[0039] This invention discloses a method for preparing biocompatible elemental selenium nanotubes, specifically comprising the following steps:

[0040] Step 1: Using anhydrous ethanol as solvent and cerium sulfate as solute, dissolve thoroughly by electromagnetic stirring to obtain a cerium sulfate ethanol solution with a concentration of 4 mmol / L.

[0041] A sodium hydroxide solution with a concentration of 5 mmol / L was obtained by using deionized water as solvent and sodium hydroxide as solute and stirring with electromagnetic stirring until fully dissolved.

[0042] Using an 80% (w / w) hydrazine hydrate solution as a dispersant, selenium powder was added and fully dispersed to obtain a selenium dispersion with a concentration of 350 mmol / L.

[0043] Step 2: Mix 12.5 ml of cerium sulfate ethanol solution, 5 ml of sodium hydroxide solution and 5 ml of selenium dispersion evenly to obtain a mixed system.

[0044] 22.5 ml of the above mixture was placed into a 50 ml hydrothermal reactor and reacted at 80 °C for 6 h.

[0045] Step 3: After the reaction is complete, the resulting reaction solution is washed four times by centrifugation with 40 ml of deionized water at a speed of 8000 rpm for 3 minutes each time. Finally, it is dried in an oven at 60℃ for 12 hours to obtain a black powder, which is elemental selenium nanotubes.

[0046] from Figure 1 The SEM images clearly show that the average length of the elemental selenium nanotubes obtained after the reaction is 12.5 ± 5 μm, and the diameter is approximately 175 nm. Therefore, the regular nanotubes in this size range prepared by this invention possess uniform morphological characteristics and stable structural properties.

[0047] Example 2

[0048] This invention discloses a method for preparing biocompatible elemental selenium nanotubes, specifically comprising the following steps:

[0049] Step 1: Using anhydrous ethanol as solvent and cerium sulfate as solute, dissolve the cerium sulfate in ethanol by electromagnetic stirring to obtain a cerium sulfate ethanol solution with a concentration of 2 mmol / L.

[0050] Using deionized water as solvent and sodium hydroxide as solute, a sodium hydroxide solution with a concentration of 3 mmol / L was obtained by electromagnetic stirring until fully dissolved.

[0051] A 70% (w / w) hydrazine hydrate solution was used as a dispersant, and selenium powder was added and fully dispersed to obtain a selenium dispersion with a concentration of 300 mmol / L.

[0052] Step 2: Mix 12.5 ml of cerium sulfate ethanol solution, 5 ml of sodium hydroxide solution and 5 ml of selenium dispersion evenly to obtain a mixed system.

[0053] 22.5 ml of the above mixture was placed into a 50 ml hydrothermal reactor and reacted at 80 °C for 2 h.

[0054] Step 3: After the reaction is complete, the resulting reaction solution is washed four times by centrifugation with 40 ml of deionized water at a speed of 8000 rpm for 3 minutes each time. Finally, it is dried in an oven at 60℃ for 12 hours to obtain a black powder, which is elemental selenium nanotubes.

[0055] from Figure 2 The SEM images clearly show that the average length of the elemental selenium nanotubes obtained after the reaction is 12±3 μm, and the diameter is approximately 150 nm. Therefore, the regular nanotubes in this size range prepared by this invention possess uniform morphological characteristics and stable structural properties.

[0056] Example 3

[0057] This invention discloses a method for preparing biocompatible elemental selenium nanotubes, specifically comprising the following steps:

[0058] Step 1: Using anhydrous ethanol as solvent and cerium sulfate as solute, dissolve thoroughly by electromagnetic stirring to obtain a cerium sulfate ethanol solution with a concentration of 4 mmol / L.

[0059] A sodium hydroxide solution with a concentration of 5 mmol / L was obtained by using deionized water as solvent and sodium hydroxide as solute and stirring with electromagnetic stirring until fully dissolved.

[0060] Using an 80% (w / w) hydrazine hydrate solution as a dispersant, selenium powder was added and fully dispersed to obtain a selenium dispersion with a concentration of 380 mmol / L.

[0061] Step 2: Mix 12.5 ml of cerium sulfate ethanol solution, 5 ml of sodium hydroxide solution and 5 ml of selenium dispersion evenly to obtain a mixed system.

[0062] 22.5 ml of the above mixture was placed into a 50 ml hydrothermal reactor and reacted at 90 °C for 2 h.

[0063] Step 3: After the reaction is complete, the resulting reaction solution is washed four times by centrifugation with 40 ml of deionized water at a speed of 8000 rpm for 3 minutes each time. Finally, it is dried in an oven at 60℃ for 12 hours to obtain a black powder, which is elemental selenium nanotubes.

[0064] from Figure 3The SEM images clearly show that the average length of the elemental selenium nanotubes obtained after the reaction is 18 ± 2.5 μm, and the diameter is approximately 400 nm. Therefore, the regular nanotubes in this size range prepared by this invention possess uniform morphological characteristics and stable structural properties.

[0065] Example 4

[0066] This invention discloses a method for preparing biocompatible elemental selenium nanotubes, specifically comprising the following steps:

[0067] Step 1: Using anhydrous ethanol as solvent and cerium sulfate as solute, dissolve thoroughly by electromagnetic stirring to obtain a cerium sulfate ethanol solution with a concentration of 4 mmol / L.

[0068] Using deionized water as solvent and sodium hydroxide as solute, a sodium hydroxide solution with a concentration of 4 mmol / L was obtained by electromagnetic stirring until fully dissolved.

[0069] Using an 80% (w / w) hydrazine hydrate solution as a dispersant, selenium powder was added and fully dispersed to obtain a selenium dispersion with a concentration of 350 mmol / L.

[0070] Step 2: Mix 12.5 ml of cerium sulfate ethanol solution, 5 ml of sodium hydroxide solution and 5 ml of selenium dispersion evenly to obtain a mixed system.

[0071] 22.5 ml of the above mixture was placed into a 50 ml hydrothermal reactor and reacted at 80 °C for 12 h.

[0072] Step 3: After the reaction is complete, the resulting reaction solution is washed four times by centrifugation with 40 ml of deionized water at a speed of 8000 rpm for 3 minutes each time. Finally, it is dried in an oven at 90℃ for 1 hour to obtain a black powder, which is elemental selenium nanotubes.

[0073] from Figure 4 The SEM images clearly show that the average length of the elemental selenium nanotubes obtained after the reaction is 10.5 ± 2 μm, and the average diameter is approximately 200 nm. Therefore, the regular nanotubes in this size range prepared by this invention possess uniform morphological characteristics and stable structural properties.

[0074] Example 5

[0075] This invention discloses a method for preparing biocompatible elemental selenium nanotubes, specifically comprising the following steps:

[0076] Step 1: Using anhydrous ethanol as solvent and cerium sulfate as solute, dissolve thoroughly by electromagnetic stirring to obtain a cerium sulfate ethanol solution with a concentration of 3 mmol / L.

[0077] Using deionized water as solvent and sodium hydroxide as solute, a sodium hydroxide solution with a concentration of 3 mmol / L was obtained by electromagnetic stirring until fully dissolved.

[0078] Using an 80% (w / w) hydrazine hydrate solution as a dispersant, selenium powder was added and fully dispersed to obtain a selenium dispersion with a concentration of 350 mmol / L.

[0079] Step 2: Mix 12.5 ml of cerium sulfate ethanol solution, 5 ml of sodium hydroxide solution and 5 ml of selenium dispersion evenly to obtain a mixed system.

[0080] 22.5 ml of the above mixture was placed into a 50 ml hydrothermal reactor and reacted at 60 °C for 6 hours.

[0081] Step 3: After the reaction is complete, the resulting reaction solution is washed four times by centrifugation with 40 ml of deionized water at a speed of 8000 rpm for 3 minutes each time. Finally, it is dried in an oven at 60℃ for 12 hours to obtain a black powder, which is elemental selenium nanotubes.

[0082] from Figure 5 The SEM images clearly show that the average length of the elemental selenium nanotubes obtained after the reaction is 10±1.5μm and the average diameter is about 150nm.

[0083] Example 6

[0084] This invention discloses a method for preparing biocompatible elemental selenium nanotubes, specifically comprising the following steps:

[0085] Step 1: Using anhydrous ethanol as solvent and cerium sulfate as solute, dissolve thoroughly by electromagnetic stirring to obtain a cerium sulfate ethanol solution with a concentration of 4 mmol / L.

[0086] A sodium hydroxide solution with a concentration of 5 mmol / L was obtained by using deionized water as solvent and sodium hydroxide as solute and stirring with electromagnetic stirring until fully dissolved.

[0087] Using an 80% (w / w) hydrazine hydrate solution as a dispersant, selenium powder was added and fully dispersed to obtain a selenium dispersion with a concentration of 380 mmol / L.

[0088] Step 2: Mix 12.5 ml of cerium sulfate ethanol solution, 5 ml of sodium hydroxide solution and 5 ml of selenium dispersion evenly to obtain a mixed system.

[0089] 22.5 ml of the above mixture was placed into a 50 ml hydrothermal reactor and reacted at 90 °C for 6 h.

[0090] Step 3: After the reaction is complete, the resulting reaction solution is washed four times by centrifugation with 40 ml of deionized water at a speed of 8000 rpm for 3 minutes each time. Finally, it is dried in an oven at 70℃ for 12 hours to obtain a black powder, which is elemental selenium nanotubes.

[0091] from Figure 6 The SEM images clearly show that the elemental selenium nanotubes obtained after the reaction have an average length of 45 μm and an average diameter of approximately 400 nm, exhibiting regular morphology and structure. This indicates that the regular nanotubes prepared in this invention possess uniform structural characteristics, laying the foundation for their application in the field of biofunctional materials.

[0092] Figure 7 This is a live cell staining image obtained from the selenium nanotubes in Example 1 of the present invention during a cell experiment. Specifically, the test results were obtained according to the following steps: L-929 cells from the mouse fibroblast cell line were co-cultured with the selenium nanotubes from Example 1 of the present invention for 24 hours, then stained with a live cell-specific staining agent. The images were observed using a fluorescence microscope; green represents live cells, and red represents dead cells. Figure 7 As shown, a large number of live cells stained with green fluorescence can be seen, with intact cell morphology and uniform distribution.

[0093] Figure 8 The image shows the staining of dead cells obtained in cell experiments using selenium nanotubes from Example 1 of this invention. It can be seen that only a very small number of dead cells emit specific fluorescence, and the proportion of dead cells is extremely low. This indicates that when the selenium nanotubes of this invention are co-cultured with L-929 cells, they do not significantly affect the survival of L-929 cells. The L-929 cells maintain a good active state, and the selenium nanotubes of this invention demonstrate excellent biocompatibility.

Claims

1. A method for preparing biocompatible elemental selenium nanotubes, characterized in that, The method comprises the following steps: S1, mixing ceric sulfate solution, sodium hydroxide solution and hydrazine hydrate selenium dispersion solution uniformly in a volume ratio of 2.5:1:1, the concentration of the ceric sulfate solution is 2-4 mmol / L, the concentration of the sodium hydroxide solution is 3-5 mmol / L, and the concentration of selenium powder in the hydrazine hydrate selenium dispersion solution is 300-380 mmol / L, to obtain a mixed system; S2, hydrothermal reaction of the mixed system at 60-90℃ for 2-12 hours to obtain a reaction liquid; S3, separation and drying of the product in the reaction liquid to obtain biocompatible elemental selenium nanotubes.

2. The method for preparing biocompatible elemental selenium nanotubes according to claim 1, characterized in that, In S1, the solvent of the ceric sulfate solution is anhydrous ethanol.

3. The method for preparing biocompatible elemental selenium nanotubes according to claim 1, characterized in that, In S1, the hydrazine hydrate selenium dispersion solution is obtained by uniformly dispersing selenium powder in a 70%-80% hydrazine hydrate solution.

4. The method for preparing biocompatible elemental selenium nanotubes according to claim 1, characterized in that, In S3, the reaction liquid is first centrifuged and washed with deionized water to obtain black powder, and the black powder is dried to obtain biocompatible elemental selenium nanotubes.

5. The method for preparing biocompatible elemental selenium nanotubes according to claim 4, characterized in that, The centrifugal washing is performed at a speed of 7800-9500 rpm for 3-5 times, each time for 1-6 minutes.

6. The method for preparing biocompatible elemental selenium nanotubes according to claim 4, characterized in that, The black powder is dried at 60-90℃ for 1-12 hours.

7. Biocompatible elemental selenium nanotubes obtained by the method for preparing biocompatible elemental selenium nanotubes according to any one of claims 1-6.

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