Hydrogel gold magnesium Janus micromotor and preparation method thereof
By sputtering a gold layer on magnesium microspheres to form a Janus-structured hydrogel gold-magnesium micromotor, the problems of autonomous movement and drug release of micromotors in biological environments were solved, efficient autonomous movement and sustained drug release were achieved, and tissue regeneration was promoted.
Patent Information
- Application Number
- CN202510814634.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-17
- Publication Date
- 2025-09-16
AI Technical Summary
Existing technologies make it difficult to achieve efficient autonomous movement of micromotors and controlled release of drugs in biological environments, and traditional methods are complex and costly.
A gold layer was sputtered on one side of the magnesium microspheres using layer-by-layer self-assembly technology to form a Janus-structured hydrogel gold-magnesium micromotor. The reaction of magnesium with water released hydrogen to drive the micromotor, and the diffusion and controlled release of the drug were achieved through the metronidazole loaded on the hydrogel.
The micromotor achieves efficient autonomous movement and sustained drug release in a biological environment, improving the therapeutic effect, especially promoting cell proliferation and tissue regeneration in the repair of chronic wounds and periodontal lesions.
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Figure CN120643504A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of metal preparation, in particular to a hydrogel gold-magnesium Janus micromotor and a preparation method thereof. Background Art
[0002] Due to their uniquely small size and excellent maneuverability, autonomous micromotors have broad application prospects in biomedicine, environmental management, chemical reaction catalysis, and other fields. Chemically driven micromotors have attracted considerable attention due to their ability to autonomously move within specific environments without requiring external energy input.
[0003] The present invention relates to a method for preparing a micromotor based on layer-by-layer self-assembly technology, and designs a hydrogel gold-magnesium Janus micromotor. By sputtering a gold layer on one side of a magnesium microsphere, a structure with typical Janus characteristics is formed, enabling the micromotor to achieve efficient autonomous motion in a variety of biological environments. This micromotor structure can release hydrogen gas by reacting with magnesium and water in an aqueous environment. The hydrogen bubbles propel the micromotor, achieving autonomous motion. Simultaneously, the hydrogel-loaded metronidazole is controllably released through diffusion and environmental response mechanisms, exerting a broad-spectrum anti-anaerobic anti-infective effect. Furthermore, the micromotor slowly releases magnesium ions during degradation, regulating the local microenvironment, promoting cell proliferation and tissue regeneration, and facilitating the repair of chronic wounds and periodontal lesions. This innovative method not only expands the application range of micromotors but also provides a new approach for drug release and delivery. Summary of the Invention
[0004] To address the shortcomings of existing technologies, the present invention provides a hydrogel gold-magnesium Janus micromotor and its preparation method. This novel synthetic micro-nanomotor offers advantages such as simple preparation, low cost, and non-toxicity. The resulting reaction product can be directly used as a drug and exhibits excellent biocompatibility. Furthermore, this micro-nanomotor can achieve sustained and controlled release of drugs while exhibiting excellent motor performance. During movement, it effectively promotes the diffusion and penetration of hydrogen and drugs into deep tissues, significantly enhancing therapeutic efficacy.
[0005] A hydrogel gold-magnesium Janus micromotor and a preparation method thereof, comprising the following steps:
[0006] S1. Evenly apply 0.8-1.2 wt % polyvinyl pyrrolidone ethanol solution on a glass slide to obtain a pretreated glass slide;
[0007] S2, dispersing magnesium particles on a pretreated glass slide to obtain a magnesium glass slide;
[0008] S3, sputtering gold particles onto a magnesium glass slide at room temperature using a vacuum sputtering device to obtain a gold-magnesium Janus micromotor slide;
[0009] S4. The composite hydrogel loaded with metronidazole is evenly coated on the gold-magnesium Janus micromotor slide by layer-by-layer self-assembly, and dried to obtain the hydrogel gold-magnesium Janus micromotor slide. The hydrogel gold-magnesium Janus micromotor slide is peeled off by ultrasonic method, centrifuged, and washed with anhydrous ethanol for 3-5 times to obtain the hydrogel gold-magnesium Janus micromotor.
[0010] Preferably, the vacuum sputtering equipment is maintained for 100-140 seconds, the sputtering current is 20 mA, and the argon pressure is 2.5 mTorr.
[0011] Preferably, the dosage ratio of the metronidazole to the composite hydrogel is 3.5-4.5 mg:1 ml.
[0012] Preferably, a composite hydrogel comprises the following steps:
[0013] The first step is to dissolve 2-amino-4-[(2-amino-2-carboxyethyl)dithio]butyric acid in pure water and N,N-dimethylformamide, add EDC / NHS crosslinker, stir at room temperature for 30-50 minutes, adjust the pH to 5-6, then add four-arm amino polyethylene glycol, keep for 3-12 hours, and finally add N,N'-thiocarbonyldiimidazole, adjust the pH to 7-9, and keep at 35-40 ° C for 20-30 hours to obtain sulfide / disulfide double-crosslinked four-arm PEG hydrogel;
[0014] In the second step, sodium alginate, pure water and sulfo / disulfide double-crosslinked four-arm PEG hydrogel are mixed to obtain a double network hydrogel, and then the double network hydrogel is placed in a 0.42-0.54wt% calcium chloride solution to obtain a composite hydrogel.
[0015] Preferably, the dosage ratio of 2-amino-4-[(2-amino-2-carboxyethyl)dithio]butyric acid, pure water, EDC / NHS crosslinker, four-arm aminopolyethylene glycol, N,N-dimethylformamide and N,N'-thiocarbonyldiimidazole in step 1 is 1.1-1.4 mg: 200 μL: 1.8-2.2 mg: 4.2-5.6 mg: 10 μL: 1 mg.
[0016] Preferably, the usage ratio of sodium alginate, pure water and sulfo / disulfide double-crosslinked four-arm PEG hydrogel in step 2 is 5 mg:380 μL:28-36 mg.
[0017] Preferably, the mixing temperature in step 2 is maintained at 35-40° C. for 1-3 hours.
[0018] Preferably, the magnesium particles have a particle size of 22±3 μm, and the purity of the vacuum sputtering gold target is 99.999%.
[0019] Beneficial effects
[0020] The present invention provides a hydrogel gold-magnesium Janus micromotor and its preparation method. Compared with the existing technology, it has the following advantages:
[0021] 1. This invention provides a vacuum sputtering method for depositing a high-purity gold layer on the surface of magnesium particles. By precisely controlling the sputtering time, current, and argon gas pressure, single-sided gold plating is achieved, forming a gold-magnesium heterostructure. This method avoids the complex interface control issues of the traditional double emulsion method.
[0022] 2. The present invention is wrapped by a double-network hydrogel. In the first network, 2-amino-4-[(2-amino-2-carboxyethyl)dithio]butyric acid, pure water, EDC / NHS crosslinker, four-arm amino polyethylene glycol, N,N-dimethylformamide and N,N'-thiocarbonyldiimidazole are reacted. The amide bond formed first provides a rigid skeleton for the hydrogel, and the sulfide bond in the thiocarbamate bond formed later gives the material redox responsiveness. In the presence of high concentrations of reducing substances (such as glutathione), the disulfide bond can be broken to regulate the crosslinking density; sodium alginate and Ca are introduced into the second network. 2+ Ionic crosslinking forms a physical crosslinking network, and the synergistic effect of the double network significantly improves the mechanical strength. BRIEF DESCRIPTION OF THE DRAWINGS
[0023] Figure 1 This is a scanning electron microscope image (SEM) of a single hydrogel gold-magnesium Janus micromotor with a diameter of approximately 20 microns in an embodiment of the present invention;
[0024] Figure 2 This is an energy dispersive X-ray spectrometer (EDX) of a single hydrogel gold-magnesium Janus micromotor with a diameter of approximately 20 microns in an embodiment of the present invention. DETAILED DESCRIPTION
[0025] 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.
[0026] Example 1
[0027] A composite hydrogel comprising the following steps:
[0028] The first step is to dissolve 2.2 mg of 2-amino-4-[(2-amino-2-carboxyethyl)dithio]butyric acid in 200 μL of pure water and 10 μL of N,N-dimethylformamide, add 1.8 mg of EDC / NHS crosslinker, stir at 25 ° C for 30-50 minutes, adjust the pH to 5-6, then add 8.4 mg of four-arm amino polyethylene glycol, keep for 3-12 hours, and finally add 2 mg of N,N'-thiocarbonyldiimidazole, adjust the pH to 7-9, and keep at 35-40 ° C for 20-30 hours to obtain sulfide / disulfide double-crosslinked four-arm PEG hydrogel;
[0029] In the second step, 10 mg of sodium alginate, 760 μL of pure water and 28 mg of sulfo / disulfide double-crosslinked four-arm PEG hydrogel were mixed, the temperature was maintained at 35°C for 1 hour to obtain a double network hydrogel, and the double network hydrogel was then placed in a 0.42 wt% calcium chloride solution to obtain a composite hydrogel.
[0030] Example 2
[0031] A composite hydrogel comprising the following steps:
[0032] The first step is to dissolve 2.8 mg of 2-amino-4-[(2-amino-2-carboxyethyl)dithio]butyric acid in 200 μL of pure water and 10 μL of N,N-dimethylformamide, add 1.8 mg of EDC / NHS crosslinker, stir at 25 ° C for 30-50 minutes, adjust the pH to 5-6, then add 10.2 mg of four-arm amino polyethylene glycol, keep for 3-12 hours, and finally add 2 mg of N,N'-thiocarbonyldiimidazole, adjust the pH to 7-9, and keep at 35-40 ° C for 20-30 hours to obtain sulfide / disulfide double-crosslinked four-arm PEG hydrogel;
[0033] In the second step, 10 mg of sodium alginate, 760 μL of pure water and 36 mg of sulfo / disulfide double-crosslinked four-arm PEG hydrogel were mixed, the temperature was maintained at 40°C for 3 hours to obtain a double network hydrogel, and the double network hydrogel was then placed in a 0.54 wt% calcium chloride solution to obtain a composite hydrogel.
[0034] Example 3
[0035] A composite hydrogel comprising the following steps:
[0036] The first step is to dissolve 2.4 mg of 2-amino-4-[(2-amino-2-carboxyethyl)dithio]butyric acid in 200 μL of pure water and 10 μL of N,N-dimethylformamide, add 4.2 mg of EDC / NHS crosslinker, stir at room temperature for 30-50 minutes, adjust the pH to 5-6, then add 9.6 mg of four-arm aminopolyethylene glycol, keep for 3-12 hours, and finally add 2 mg of N,N'-thiocarbonyldiimidazole, adjust the pH to 7-9, and keep at 35-40 ° C for 20-30 hours to obtain sulfide / disulfide double-crosslinked four-arm PEG hydrogel;
[0037] In the second step, 10 mg of sodium alginate, 760 μL of pure water and 30 mg of sulfo / disulfide double-crosslinked four-arm PEG hydrogel were mixed, the temperature was maintained at 38°C for 2 hours to obtain a double network hydrogel, and the double network hydrogel was then placed in a 0.5 wt% calcium chloride solution to obtain a composite hydrogel.
[0038] Example 4
[0039] A method for preparing a hydrogel gold-magnesium Janus micromotor comprises the following steps:
[0040] S1. Evenly apply 0.8 wt % polyvinyl pyrrolidone ethanol solution on a glass slide to obtain a pretreated glass slide;
[0041] S2, dispersing magnesium particles on a pretreated glass slide to obtain a magnesium glass slide;
[0042] S3, sputtering gold microparticles onto a magnesium glass slide using a vacuum sputtering device at room temperature. The vacuum sputtering device is maintained for 100 seconds with a sputtering current of 20 mA and an argon pressure of 2.5 mTorr to obtain a glass slide containing gold-magnesium Janus micromotors;
[0043] S4. The composite hydrogel loaded with metronidazole was evenly coated on the gold-magnesium Janus micromotor slide by layer-by-layer self-assembly, and dried to obtain the hydrogel gold-magnesium Janus micromotor slide. The hydrogel gold-magnesium Janus micromotor slide was peeled off by ultrasonic method, centrifuged, and washed with anhydrous ethanol three times to obtain the hydrogel gold-magnesium Janus micromotor.
[0044] The dosage ratio of metronidazole and composite hydrogel is 3.5 mg:1 ml.
[0045] The particle size of the magnesium particles is 22±3 μm, and the purity of the vacuum sputtering gold target is 99.999%.
[0046] Example 5
[0047] A method for preparing a hydrogel gold-magnesium Janus micromotor comprises the following steps:
[0048] S1. Evenly apply 1.2 wt % polyvinyl pyrrolidone ethanol solution on a glass slide to obtain a pretreated glass slide;
[0049] S2, dispersing magnesium particles on a pretreated glass slide to obtain a magnesium glass slide;
[0050] S3, sputtering gold microparticles onto a magnesium glass slide at room temperature using a vacuum sputtering device. The vacuum sputtering device is maintained for 140 seconds with a sputtering current of 20 mA and an argon pressure of 2.5 mTorr to obtain a glass slide containing gold-magnesium Janus micromotors.
[0051] S4. The composite hydrogel loaded with metronidazole was evenly coated on the gold-magnesium Janus micromotor slide by layer-by-layer self-assembly, and dried to obtain the hydrogel gold-magnesium Janus micromotor slide. The hydrogel gold-magnesium Janus micromotor slide was peeled off by ultrasonic method, centrifuged, and washed with anhydrous ethanol 5 times to obtain the hydrogel gold-magnesium Janus micromotor.
[0052] The dosage ratio of metronidazole and composite hydrogel is 4.5 mg:1 ml.
[0053] The particle size of the magnesium particles is 22±3 μm, and the purity of the vacuum sputtering gold target is 99.999%.
[0054] Example 6
[0055] A method for preparing a hydrogel gold-magnesium Janus micromotor comprises the following steps:
[0056] S1. Evenly apply 1 wt% polyvinyl pyrrolidone ethanol solution on a glass slide to obtain a pretreated glass slide;
[0057] S2, dispersing magnesium particles on a pretreated glass slide to obtain a magnesium glass slide;
[0058] S3, sputtering gold microparticles onto a magnesium glass slide at room temperature using a vacuum sputtering device. The vacuum sputtering device is maintained for 120 seconds with a sputtering current of 20 mA and an argon pressure of 2.5 mTorr to obtain a glass slide containing gold-magnesium Janus micromotors.
[0059] S4. The composite hydrogel loaded with metronidazole was evenly coated on the gold-magnesium Janus micromotor slide by layer-by-layer self-assembly, and dried to obtain the hydrogel gold-magnesium Janus micromotor slide. The hydrogel gold-magnesium Janus micromotor slide was peeled off by ultrasonic method, centrifuged, and washed with anhydrous ethanol 4 times to obtain the hydrogel gold-magnesium Janus micromotor.
[0060] The dosage ratio of metronidazole and composite hydrogel is 4 mg:1 ml.
[0061] The particle size of the magnesium particles is 22±3 μm, and the purity of the vacuum sputtering gold target is 99.999%.
[0062] It should be noted that, in this document, relational terms such as first and second, etc., are used only to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any actual relationship or order between these entities or operations. Moreover, the terms "comprises," "comprising," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that includes a list of elements includes not only those elements but also other elements not explicitly listed, or elements inherent to such process, method, article, or apparatus.
[0063] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.
Claims
1. A method for preparing a hydrogel gold-magnesium Janus micromotor, characterized by: The method comprises the following steps: S1. Evenly apply 0.8-1.2 wt % polyvinyl pyrrolidone ethanol solution on a glass slide to obtain a pretreated glass slide; S2, dispersing magnesium particles on a pretreated glass slide to obtain a magnesium glass slide; S3, sputtering gold particles onto a magnesium glass slide at room temperature using a vacuum sputtering device to obtain a gold-magnesium Janus micromotor slide; S4. The composite hydrogel loaded with metronidazole is evenly coated on the gold-magnesium Janus micromotor slide by layer-by-layer self-assembly, and dried to obtain the hydrogel gold-magnesium Janus micromotor slide. The slide is then peeled off by ultrasonic method, centrifuged, and washed with anhydrous ethanol for 3-5 times to obtain the hydrogel gold-magnesium Janus micromotor.
2. The method for preparing a hydrogel gold-magnesium Janus micromotor according to claim 1, characterized in that: The vacuum sputtering equipment was maintained for 100-140 seconds, the sputtering current was 20 mA, and the argon pressure was 2.5 mTorr.
3. The method for preparing a hydrogel gold-magnesium Janus micromotor according to claim 1, characterized in that: The dosage ratio of the metronidazole to the composite hydrogel is 3.5-4.5 mg:1 ml.
4. The method for preparing a hydrogel gold-magnesium Janus micromotor according to claim 1, characterized in that: The composite hydrogel comprises the following steps: The first step is to dissolve 2-amino-4-[(2-amino-2-carboxyethyl)dithio]butyric acid in pure water and N,N-dimethylformamide, add EDC / NHS crosslinker, stir at room temperature for 30-50 minutes, adjust the pH to 5-6, then add four-arm amino polyethylene glycol, keep for 3-12 hours, and finally add N,N'-thiocarbonyldiimidazole, adjust the pH to 7-9, and keep at 35-40 ° C for 20-30 hours to obtain sulfide / disulfide double-crosslinked four-arm PEG hydrogel; In the second step, sodium alginate, pure water and sulfo / disulfide double-crosslinked four-arm PEG hydrogel are mixed to obtain a double network hydrogel, and then the double network hydrogel is placed in a 0.42-0.54wt% calcium chloride solution to obtain a composite hydrogel.
5. The method for preparing a hydrogel gold-magnesium Janus micromotor according to claim 3, characterized in that: The dosage ratio of 2-amino-4-[(2-amino-2-carboxyethyl)dithio]butyric acid, pure water, EDC / NHS crosslinker, four-arm aminopolyethylene glycol, N,N-dimethylformamide and N,N'-thiocarbonyldiimidazole in step 1 is 1.1-1.4 mg: 200 μL: 1.8-2.2 mg: 4.2-5.6 mg: 10 μL: 1 mg.
6. The method for preparing a hydrogel gold-magnesium Janus micromotor according to claim 3, characterized in that: The usage ratio of sodium alginate, pure water and sulfo / disulfide double-crosslinked four-arm PEG hydrogel in step 2 is 5 mg:380 μL:28-36 mg.
7. The method for preparing a hydrogel gold-magnesium Janus micromotor according to claim 3, characterized in that: The mixing temperature in step 2 is maintained at 35-40° C. for 1-3 hours.
8. The method for preparing a hydrogel gold-magnesium Janus micromotor according to claim 1, characterized in that: The magnesium particles have a particle size of 22±3 μm, and the purity of the vacuum sputtering gold target is 99.999%.