Micromotor and method for its preparation and use
The segmented tubular micromotor composed of Au and Zn elements solves the problems of low drug delivery efficiency and biocompatibility, achieving longer drug delivery time and cell targeting, improving therapeutic efficacy and safety, and is suitable for cardiac drug applications.
Patent Information
- Application Number
- CN202411326853.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-23
- Publication Date
- 2025-11-11
- Estimated Expiration
- 2044-09-23
AI Technical Summary
Existing micromotors have low drug delivery efficiency and difficulty in achieving precise targeting in targeted drug delivery. Drug carrier materials have biocompatibility and safety issues, insufficient control over drug release rate and duration, and lack of real-time monitoring and feedback mechanisms, which affect treatment efficacy and safety.
A segmented tubular micromotor composed of Au and Zn elements is used. Zn is enriched in the driving section to form a concentration gradient that drives the motion. Combined with an electrochemical deposition method, the stability and biocompatibility of the micromotor are ensured.
It achieves longer drug delivery time and higher cell targeting, improves treatment efficacy, reduces the risk of side effects, and has real-time monitoring and feedback capabilities, making it suitable for cardiac drug applications.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of micromotor technology, and in particular to a micromotor, its fabrication method, and its application. Background Technology
[0002] The heart is a vital organ in the human body. A heartbeat pumps blood to all parts of the body, enabling cells to maintain normal metabolism and function. The sinoatrial node, also known as the sinus node, is normally the heart's pacemaker. When this node malfunctions, a pacemaker is often implanted to stimulate the heart and restore a normal heart rate. However, pacemakers are powered by electrochemical batteries, resulting in a limited lifespan and susceptibility to electrode malfunction or interference from external electromagnetic fields.
[0003] Micromotors are micrometer-scale power devices that convert energy from the external environment into their own kinetic energy, showing broad application prospects in targeted drug delivery, precision medicine, biosensing, and environmental remediation. Due to their small size, micromotors can follow blood flow, and their size can be adjusted to influence their distribution in various organs. If micromotors can be used for mechanical or chemical stimulation of the myocardium, surgical trauma can be avoided, treatment efficacy improved, and side effects reduced.
[0004] Existing micromotors still have the following drawbacks in targeted drug delivery: (1) low drug delivery efficiency, making it difficult to achieve precise targeting, resulting in unstable treatment effects and increased risk of side effects; (2) biocompatibility and safety issues with drug carrier materials, which may cause immune reactions or other adverse reactions; (3) insufficient control over the drug release rate and duration by traditional drug delivery systems, affecting treatment effects; (4) poor durability and stability of drug carriers in complex in vivo environments, which may lead to drug degradation or inactivation; In addition, there is still a lack of effective real-time monitoring and feedback mechanisms, making it difficult to accurately assess the distribution and effects of drugs after they enter the body, resulting in the inability to adjust treatment plans in a timely manner, which greatly limits the application of micromotors in cardiac drugs. Summary of the Invention
[0005] The present invention aims to at least solve one of the aforementioned technical problems existing in the prior art. Therefore, one objective of the present invention is to provide a micromotor; a second objective is to provide a method for manufacturing such a micromotor; and a third objective is to provide applications of such a micromotor.
[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows:
[0007] A first aspect of the present invention provides a micromotor, the elemental composition of which includes Au and Zn; the mass ratio of Au to Zn is 1:(3-5).
[0008] Preferably, the mass ratio of Au to Zn is 1:(3-4).
[0009] Preferably, the micromotor is composed of Au and Zn elements; the mass ratio of Au to Zn elements is 1:(3-4).
[0010] Preferably, the micromotor has a segmented tubular structure.
[0011] Preferably, the length of the micromotor is 1-8 μm; more preferably, the length of the micromotor is 3-6 μm.
[0012] Preferably, the diameter (outer diameter) of the circular cross-section of the micromotor is 100-400 nm; more preferably, the diameter (outer diameter) of the circular cross-section of the micromotor is 200-250 nm.
[0013] Preferably, the segmented tubular micromotor includes a stabilizing section and a driving section; the Au element is enriched in the stabilizing section (Au section); and the Zn element is enriched in the driving section (Zn section).
[0014] Preferably, the length of the stabilizing segment is 1-2 μm; more preferably, the length of the stabilizing segment is 1-1.5 μm.
[0015] Preferably, the length of the driving segment is 2-4 μm; more preferably, the length of the driving segment is 2-2.5 μm.
[0016] Preferably, there is a clear dividing line between the stable section and the driving section.
[0017] Specifically, the micromotor provided by this invention is composed of Au and Zn elements, with Zn being the dominant element, making it an Au / Zn composite micromotor. Au and Zn elements are enriched at both ends, forming a stable segment (Au segment) and a driving segment (Zn segment) with a clear boundary. In the Zn segment, Zn is oxidized to Zn2. 2+ With Zn 2+ Gradually accumulating, a concentration gradient eventually forms in the Zn segment, prompting the motor to move. The micromotor provided by this invention is driven by the Zn segment concentration gradient. The higher Zn element content and the longer driving segment (Zn segment) length can provide the micromotor with a longer movement time.
[0018] Preferably, the average speed of the micromotor moving in deionized water is 3-8 μm / s; more preferably, the average speed of the micromotor moving in deionized water is 4-6 μm / s.
[0019] Preferably, the range of motion of the micromotor in deionized water is (15-30) × (15-30) μm. 2 More preferably, the range of motion of the micromotor in deionized water is (15-25)×(15-25)μm. 2 .
[0020] Preferably, the zeta potential of the micromotor is -25 to -18 mV; more preferably, the zeta potential of the micromotor is -23 to -19 mV.
[0021] A second aspect of the present invention provides a method for fabricating the micromotor described in the first aspect of the present invention, comprising the following steps:
[0022] S1. A gold nanolayer is deposited on the surface of a polycarbonate film with a porous structure to obtain a gold-plated polycarbonate film.
[0023] S2. Using the gold-plated polycarbonate film as the working electrode, Au and Zn are electrochemically deposited sequentially.
[0024] S3. Remove the gold-plated polycarbonate film to obtain the micron motor.
[0025] Preferably, in step S1, the pore size of the polycarbonate film is 300-450 nm; more preferably, the pore size of the polycarbonate film is 370-420 nm.
[0026] Preferably, in step S1, the pore length of the polycarbonate film is 10-16 mm; more preferably, the pore length of the polycarbonate film is 12-15 mm.
[0027] Preferably, in step S1, the gold layer thickness of the gold-plated polycarbonate film is 150-250 nm; more preferably, the gold layer thickness of the gold-plated polycarbonate film is 170-220 nm.
[0028] Preferably, in step S1, the vapor deposition is performed in a vacuum evaporation vapor deposition machine.
[0029] Preferably, in step S1, the specific operation of the vapor deposition is as follows: the polycarbonate film is fixed to the substrate, placed in the vapor deposition chamber, gold particles are placed in the evaporation tank, and the chamber is evaporated after being evaporated.
[0030] Preferably, the amount of gold used is 0.5-1.5g; more preferably, the amount of gold used is 0.7-1.2g.
[0031] Preferably, the vacuum degree of the cavity is ≤1×10⁻⁶. -4 After Pa, vapor deposition begins.
[0032] Preferably, in step S1, the evaporation process of the gold nanolayer is as follows: firstly, using... A gold layer with a thickness of 15-50 nm is deposited at a rate of [missing information]; then [missing information] The gold nanolayer is further deposited at a rate of 150-250 nm; more preferably, the deposition process of the gold nanolayer is as follows: first, at a rate of 150-250 nm; A gold layer with a thickness of 15-30 nm is deposited at a rate of [missing information]; then [missing information] The deposition rate continues to be increased to 150-250 nm.
[0033] Specifically, the gold nanolayers are deposited using a programmed speed-up evaporation method, which enables the gold nanolayers and polycarbonate films to adhere more tightly.
[0034] Preferably, in step S2, the electrochemical deposition uses a three-electrode system, wherein the counter electrode is a platinum electrode and the reference electrode is an Ag / AgCl electrode.
[0035] Preferably, in step S2, during the electrochemical deposition of Au, the electroplating solution contains sodium gold sulfite; more preferably, the electroplating solution contains sodium gold sulfite.
[0036] Preferably, in step S2, the deposition voltage during the electrochemical deposition of Au is -0.5-1.5V; more preferably, the deposition voltage is -0.8-1.2V.
[0037] Preferably, in step S2, the deposition time for electrochemically depositing Au is 5-15 min; more preferably, the deposition time is 7-12 min.
[0038] Preferably, in step S2, during the electrochemical deposition of Zn, the electroplating solution is a mixture of Zn salt and H3BO3.
[0039] Preferably, the Zn salt comprises ZnSO4·7H2O.
[0040] Preferably, in the Zn salt and H3BO3 mixture, the initial concentration ratio of Zn salt to H3BO3 is (1-3):1; more preferably, the initial concentration ratio of Zn salt to H3BO3 is (1.5-2.5):1.
[0041] Preferably, the amount of the Zn salt and H3BO3 mixture is 40-60 mL; more preferably, the amount of the Zn salt and H3BO3 mixture is 45-55 mL.
[0042] Preferably, in step S2, the deposition voltage during the electrochemical deposition of Zn is -2 to -1V; more preferably, the deposition voltage is -1.5 to -1V.
[0043] Preferably, in step S2, the deposition time for electrochemically depositing Zn is 5-15 min; more preferably, the deposition time is 7-12 min.
[0044] Preferably, the specific operation of electrochemical deposition of Au and Zn is as follows: placing a gold-plated polycarbonate film into an electrodeposition support, connecting it to an electrochemical workstation, pouring in a gold plating solution to completely immerse the electrodeposition support, depositing Au, rinsing the electrode with deionized water; pouring in an electroplating solution, depositing Zn, and removing the gold-plated polycarbonate film with deposited Au and Zn from the electrodeposition support to obtain the micron motor.
[0045] Preferably, in step S3, the method for removing the gold-plated polycarbonate film includes physical wiping and solution dissolution.
[0046] Preferably, the physical removal includes grinding a gold-plated polycarbonate film on frosted glass to remove the nano-gold layer.
[0047] Preferably, the solution dissolution includes adding a solution to dissolve the polycarbonate film.
[0048] Preferably, the solution includes at least one of dichloromethane and tetrahydrofuran.
[0049] Preferably, in step S3, after removing the gold-plated polycarbonate film, the operation of washing the micron motor is also included.
[0050] Preferably, the reagents used for washing include ethanol and deionized water.
[0051] The third aspect of the invention provides the application of the micromotor described in the first aspect of the invention in cardiac medications.
[0052] Compared with the prior art, the beneficial effects of the present invention are:
[0053] 1) The micro motor provided by this invention includes Au and Zn elements, with Zn element content being dominant. The micro motor has a segmented tubular structure with obvious dividing lines between segments. The higher content of Zn element is enriched to form Zn segments, and the concentration gradient is used to make the Zn segments act as driving segments to drive the motor. The higher Zn element content and the longer driving segment (Zn segment) length can provide the micro motor with a longer movement time, while the Au segment improves the cell targeting of the motor.
[0054] 2) The micron motor preparation method provided by this invention is simple, the process conditions are mild, and it is suitable for industrial application.
[0055] 3) The micron motor provided by this invention has high biosafety and can effectively stimulate mouse cardiomyocytes to induce calcium metabolism. 2+The increased concentration indicates that it has good application prospects as a cardiac drug. Attached Figure Description
[0056] Figure 1 The image shows a cold field emission electron microscope (SEM) image of the Au / Zn composite micromotor in the example.
[0057] Figure 2 This is an elemental distribution diagram of the Au / Zn composite micromotor in the example embodiment;
[0058] Figure 3 The elemental spectrum of the Au / Zn composite micromotor in the example is shown below;
[0059] Figure 4 A statistical analysis graph showing the length and diameter of the Au / Zn composite micromotor in the example;
[0060] Figure 5 This is a Zeta potential diagram of the Au / Zn composite micromotor in the example;
[0061] Figure 6 The graph shows the motion performance analysis of the Au / Zn composite micro motor in deionized water in this example.
[0062] Figure 7 Calcein-AM / PI staining image of the co-culture experiment of Au / Zn composite micromotor and mouse cardiomyocytes in the example;
[0063] Figure 8 The cell survival rate in the co-culture experiment of Au / Zn composite micromotor and mouse cardiomyocytes in the example;
[0064] Figure 9 Example of adding Ca to mouse cardiomyocytes: Au / Zn composite micromotor 2 Graph of fluorescence intensity changes;
[0065] Figure 10 For mouse cardiomyocytes Ca 2+ Graph showing the change in average fluorescence intensity over time. Detailed Implementation
[0066] The present invention will be further described in detail below through specific embodiments. Unless otherwise specified, the raw materials, reagents, or apparatus used in the embodiments can be obtained from conventional commercial sources or by existing technical methods. Unless otherwise specified, the experimental or testing methods are conventional methods in the art.
[0067] The raw material information used in the embodiments is shown in Table 1:
[0068] Table 1. Raw material information used in the embodiments.
[0069] raw material Purchase manufacturer / model polycarbonate film Waterman, 400nm, 13mm Ag / AgCl electrode Shanghai Titan Technology Co., Ltd. platinum wire electrode Shanghai Titan Technology Co., Ltd. Gold plating solution containing sodium gold sulfite DeepBlue Technology (Shanghai) Co., Ltd., 24k Gold Water <![CDATA[Zinc sulfate heptahydrate (ZnSO4·7H2O)]]> Aladdin <![CDATA[Boric acid (H3BO3)]]> Aladdin <![CDATA[methylene chloride (CH2Cl2)]]> Aladdin PBS buffer Thermo Fisher Chinese name: Calcein-AM (calcein acetoxymethyl ester) Shanghai Beyotime Biotechnology Co., Ltd. Propidium iodide (PI) Shanghai Beyotime Biotechnology Co., Ltd. Fetal bovine serum (FBS) Shanghai Beyotime Biotechnology Co., Ltd. Dual resistance Shanghai Beyotime Biotechnology Co., Ltd. glutamine Thermo Fisher trypsin-EDTA solution Shanghai Beyotime Biotechnology Co., Ltd. MEM culture medium Thermo Fisher Mouse cardiomyocytes (HL-1) Shanghai Beyotime Biotechnology Co., Ltd.
[0070] Example
[0071] This embodiment provides an Au / Zn composite micromotor, composed of Au and Zn elements in a mass ratio of 1:4. The preparation steps are as follows:
[0072] S11. Fix the polycarbonate film (400nm, 13mm) onto the substrate, then place it into the evaporation chamber of a vacuum evaporation deposition machine. Add 1g of gold particles to the evaporation tank and wait for the chamber to be evacuated. Wait until the vacuum level inside the chamber is ≤1×10⁻⁶. -4 Evaporation begins at Pa. A 20nm thick gold layer was deposited at a evaporation rate, and then the evaporation rate was increased to [a higher rate]. After depositing a 200 nm gold nanolayer, the deposition process was stopped to obtain a gold-plated polycarbonate film, which was used as a template for fabricating a micromotor.
[0073] S21. A micromotor is prepared using an electrochemical deposition method with a three-electrode system. The counter electrode is a platinum wire, the reference electrode is Ag / AgCl, and the working electrode is the gold-plated polycarbonate film prepared in step S11. The gold-plated polycarbonate film is placed in an electrodeposition holder, connected to an electrochemical workstation, and gold plating solution is poured in to completely immerse the electrodeposition holder. Deposition is performed at a constant voltage of -0.9V for 10 minutes, and then the electrode is removed and rinsed with deionized water. Using deionized water as a solvent, 50 mL of a mixed solution of 0.2 mol / L ZnSO4·7H2O and 0.1 mol / L H3BO3 is prepared as a zinc electroplating solution. Deposition is performed at a constant voltage of -1.230V for 10 minutes, and then the gold-plated polycarbonate film with Au and Zn deposited is removed from the electrodeposition holder.
[0074] S31. The gold-plated polycarbonate film deposited with Au and Zn was ground on frosted glass to remove the nano-gold layer (applying appropriate pressure to avoid damaging the motor structure, rinsing several times with deionized water during the process, stopping after the gold material was completely ground). CH2Cl2 was added to dissolve the polycarbonate film to release the micromotor. The solution was washed twice with ethanol and deionized water by ultrasonic centrifugation, finally obtaining the Au / Zn composite micromotor dispersed in deionized water.
[0075] Material characterization and performance testing
[0076] 1. Structural and morphological characterization of Au / Zn composite micromotor:
[0077] (1) The Au / Zn composite micromotors in the examples were added to deionized water and ultrasonically dispersed. 10 μL of the solution was coated onto the silicon wafer of the conductive adhesive on the sample stage and dried in a vacuum oven at 50 °C for 3 h. ① The morphology of the Au / Zn composite micromotors was observed using a cold field emission electron microscope (S-4800, Hitachi, Japan); ② Elemental analysis of the Au / Zn composite micromotors was performed using an energy-dispersive X-ray spectrometer (EDX) with an accelerating voltage of 10 kV and a probe working distance of 8 mm; ③ The length and diameter of 30 Au / Zn composite micromotors were statistically analyzed using ImageJ software.
[0078] Figure 1 The image shown is a cold field emission electron microscope (SEM) image of the Au / Zn composite micromotor from the example embodiment. Figure 1 As can be seen, the Au / Zn composite micromotor prepared in the examples has a segmented tubular structure with a relatively regular shape and obvious dividing lines between segments.
[0079] Figure 2 The image shows the elemental distribution of the Au / Zn composite micromotor in the example, where, Figure 2 (a) is a composite element response diagram. Figure 2 (b) is the response diagram of the Au element. Figure 2 (c) is the response diagram of Zn element; Figure 3 This is the elemental spectrum of the Au / Zn composite micromotor used in this example. Figure 2 and Figure 3 As can be seen, the Au / Zn composite micromotor prepared in the examples is composed of Au and Zn elements, with Zn content exceeding Au content, and Zn content being dominant, with a mass ratio of approximately (3-4):1 to Au. In the segmented tubular structure, the Zn segment is relatively long and serves as the driving segment. The higher Zn content and the longer driving segment (Zn segment) length are beneficial for providing the micromotor with a longer motion time.
[0080] Figure 4 The following is a statistical analysis chart showing the length and diameter of the Au / Zn composite micromotor in the example. Figure 4 (a) is a length statistics analysis chart. Figure 4 (b) is a statistical analysis chart of diameter. (From...) Figure 4It is known that the length distribution range of the Au / Zn composite micromotors prepared in the examples is 1-8 μm, mainly concentrated in the 3-6 μm range; the diameter (outer diameter) distribution range of the circular cross-section of the Au / Zn composite micromotors is 100-400 nm, mainly concentrated in the 200-250 nm range. The size distribution range of the Au / Zn composite micromotors is relatively wide. By adjusting the pore size and length of the polycarbonate film during the preparation process, the size of the micromotor template can be adjusted, thereby controlling the size of the micromotor and affecting its distribution in vivo or other environments.
[0081] (2) The Au / Zn composite micro motor was ultrasonically dispersed in deionized water, added to the sample cell, and the Zeta potential of the Au / Zn composite micro motor was measured using a Malvern particle size analyzer.
[0082] Figure 5 The Zeta potential diagram of the Au / Zn composite micromotor in the example is shown below. Figure 5 It can be seen that the Zeta potential of the Au / Zn composite micromotor prepared in the examples is -19.73mV. The value of the Zeta potential is related to the stability of the colloidal dispersion. The larger the absolute value of the Zeta potential, the more stable the system. The larger the absolute value of the Zeta potential of the Au / Zn composite micromotor provided by the present invention, the greater the charge repulsion between the micromotors, which can effectively prevent the aggregation of micromotors and has good dispersion stability.
[0083] 2. Motion performance analysis of Au / Zn composite micro motor:
[0084] In the example, the Au / Zn composite micromotor was added to deionized water and ultrasonically dispersed. The movement of the micromotor in the deionized water was observed and video recorded under an inverted fluorescence microscope (Nikon Ti2-A, Nikon Corporation) at a frame rate of 10 frames per second. Ten micromotors were selected from the video, and the motion path of the micromotor within 10 seconds was analyzed using the manual sampling function of ImageJ. Then, the motion trajectory of the micromotor was normalized using the Chemotaxis tool to analyze the length of the motor's motion trajectory and calculate the motor's speed.
[0085] Figure 6 The graph shows the motion performance analysis of the Au / Zn composite micromotor in deionized water, as illustrated in the example. Figure 6 It can be seen that the average speed of the Au / Zn composite micromotor in deionized water is 4.51 μm / s, with a directionality of 0.11; the movement path of the micromotor is elliptical, and it can be relatively stable within a 20×20 μm radius. 2 The movement within the range indicates that a single micromotor can exert a sustained effect on cells within that range.
[0086] 3. Biocompatibility testing of Au / Zn composite micromotor:
[0087] The Au / Zn composite micromotor was co-cultured with mouse cardiomyocytes (HL-1) in the example, and cell viability was assessed by fluorescence staining to evaluate the biocompatibility of the Au / Zn composite micromotor. 5000 cells were seeded in each of nine culture dishes and cultured for 72 h at 37°C and 5% CO2. Then, 10 μL of Au / Zn composite micromotor dispersed in PBS buffer was added to each dish, shaken to ensure even dispersion, and then the dishes were placed in an incubator. Cell viability was assessed by fluorescence staining at 0 h, 24 h, and 48 h. Specifically, the cell culture medium was discarded, a mixture of Calcein-AM and PI was added, the dishes were incubated in an incubator for 30 min, and observed under an inverted fluorescence microscope.
[0088] Figure 7 This image shows Calcein-AM / PI staining results from the co-culture experiment of Au / Zn composite micromotors and mouse cardiomyocytes in this example. The Calcein-AM / PI staining scale is 100 μm. From left to right, the images represent the bright field, FITC-labeled fluorescence field, Texas Red-labeled fluorescence field, and the merged image. From top to bottom, the images represent the time points for detecting cell viability (h0, h24, and h48). Figure 7 It can be seen that in bright field, mouse cardiomyocytes are spindle-shaped, indicating that the cardiomyocytes are well attached to the wall, and several Au / Zn composite micromotors are located near the cells; FITC fluorescence field, Texas Red fluorescence field and Merge plot show that the vast majority of cells are in a viable state within 1-48 hours.
[0089] Figure 8 The cell viability in the co-culture experiment of Au / Zn composite micromotor and mouse cardiomyocytes in the example was determined by... Figure 8 It can be seen that the survival rate of mouse cardiomyocytes (HL-1) in the initial culture period (0h) was 99.53%, the survival rate in the 24th hour of co-culture was 98.14%, and the survival rate in the 48th hour of co-culture was 96.89%. The survival rate was high in the period from 0 to 48 hours. Moreover, the survival rate of cardiomyocytes near the micromotor was significantly higher than that of other cells, indicating that the Au / Zn composite micromotor provided by the present invention has good biocompatibility.
[0090] 4. Au / Zn composite micromotor stimulation of mouse cardiomyocytes experiment:
[0091] 1) Culture of mouse cardiomyocytes (HL-1): Mouse cardiomyocytes (HL-1) were cultured in MEM medium supplemented with 10% fetal bovine serum, 1% penicillin-drug antibiotics, and 1% glutamine. The culture flasks were placed in a 37°C, 5% CO2 incubator. The cells were observed every two days using an optical microscope, and the culture medium was changed: waste medium was discarded, cells were washed with PBS buffer, and the prepared complete culture medium was added again. When the cell density reached 80%, the cells were digested with trypsin-EDTA solution, centrifuged at 1000 rpm for 4 min, resuspended in complete culture medium, and passaged. The cell suspension was seeded into culture dishes for subsequent experiments, and the cells were also aliquoted into culture flasks for later use.
[0092] 2) Au / Zn composite micromotor stimulation of mouse cardiomyocytes (HL-1): Remove MEM cell culture medium, wash cells with PBS buffer, and add PBS buffer and Ca... 2+ Fluorescent dyes were used to stain cells after incubation at 37°C for 30 min in a cell culture incubator. The fluorescent staining solution was removed, and the cells were washed with glucose solution. 1 mL of glucose solution was added, and the cells were observed under an inverted fluorescence microscope. 5 μL of an Au / Zn composite micromotor (dispersed in glucose solution) was added, and cell images were observed and recorded. Images of the cells after adding the Au / Zn composite micromotor were also recorded. Ca2+ was observed using the FITC channel. 2+ The change of fluorescent dye reaction over time was observed. The average fluorescence intensity of the fluorescence spectrum was analyzed using ImageJ software.
[0093] Figure 9 Example of adding Ca to mouse cardiomyocytes: Au / Zn composite micromotor 2+ The fluorescence intensity change graph, Figure 10 For mouse cardiomyocytes Ca 2+ A graph showing the change in average fluorescence intensity over time. Figure 9 and Figure 10 It can be seen that after adding the Au / Zn composite micromotor of the example to the cell solution, the Ca2+ in mouse cardiomyocytes increased. 2+ The fluorescence intensity gradually increases, reaching its peak at 30 s. Afterward, due to fluorescence quenching, the fluorescence intensity gradually weakens, but at 285 s, the Ca... 2+ The fluorescence intensity remained higher than that at 0s. Fluorescence intensity is related to intracellular Ca2+. 2+ The concentrations were positively correlated; after adding the Au / Zn composite micromotor in the example, the Ca concentration was... 2 Increased fluorescence intensity of + indicates intracellular Ca2+ in mouse cardiomyocytes 2+ The concentration increases.
[0094] In the process of excitation-contraction coupling in cardiomyocytes, the cardiomyocyte first generates an action potential, followed by L-type Ca2+ on the T-tubules of the cardiomyocyte. 2+ L-type Ca2+ channels open, allowing extracellular Ca2+ to enter. 2+ influx, influx of Ca 2+ A portion of the calcium release pathway binds to Ryanodine receptors (RyR) located in the endoplasmic reticulum / sarcoplasmic reticulum, releasing calcium from the sarcoplasmic reticulum. 2+ This causes intracellular Ca to... 2+ As the concentration increases, Ca 2+ It binds to troponin, triggering the binding and sliding of cross-bridges on thick filaments with thin filaments, thereby inducing contraction. Considering that in cardiomyocytes, intracellular calcium... 2+ Increased concentration means intracellular Ca 2+ The release and activation of mitochondria, while Ca 2+ It is a messenger involved in a variety of cellular processes, including protein expression, cell differentiation, and cell motility. In cardiomyocytes, Ca2+... 2+ Increased concentration is typically associated with contraction, which plays a crucial role in heartbeat. The Au / Zn composite micromotor provided by this invention exhibits good biocompatibility and can effectively stimulate mouse cardiomyocytes to increase Ca2+ concentration. 2+ The increased concentration indicates that it has good application prospects as a cardiac drug.
Claims
1. A micrometer motor, characterized in that, The micromotor is composed of Au and Zn; the mass ratio of Au to Zn is 1:(3-5). The micromotor has a segmented tubular structure with a length of 1-8µm and a circular cross-section diameter of 100-400nm. The segmented tubular micromotor includes a stable section and a driving section; the Au element is enriched in the stable section; the Zn element is enriched in the driving section; the length of the stable section is 1-2 µm; the length of the driving section is 2-4 µm.
2. The method for preparing the micromotor according to claim 1, characterized in that, Includes the following steps: S1. A gold nanolayer is deposited on the surface of a polycarbonate film with a porous structure to obtain a gold-plated polycarbonate film. S2. Using the gold-plated polycarbonate film as the working electrode, Au and Zn are electrochemically deposited sequentially. S3. Remove the gold-plated polycarbonate film to obtain the micron motor.
3. The preparation method according to claim 2, characterized in that, In step S1, the pore size of the polycarbonate film is 300-450 nm.
4. The preparation method according to claim 2, characterized in that, In step S1, the gold nanolayer deposition process is as follows: first, a gold layer with a thickness of 15-50 nm is deposited at a rate of 0.3-0.7 Å / s; then, the deposition continues at a rate of 0.8-1.2 Å / s to a thickness of 150-250 nm.
5. The preparation method according to claim 2, characterized in that, In step S2, the electrochemical deposition uses a three-electrode system, wherein the counter electrode is a platinum electrode and the reference electrode is an Ag / AgCl electrode.
6. The preparation method according to claim 2, characterized in that, In step S2, during the electrochemical deposition of Au, the electroplating solution contains gold sulfite; the deposition voltage is -0.5-1.5V; and the deposition time is 5-15min.
7. The preparation method according to claim 2, characterized in that, In step S2, during the electrochemical deposition of Zn, the electroplating solution is a mixture of Zn salt and H3BO3; the deposition voltage is -2 to -1V; and the deposition time is 5-15 minutes.
8. The preparation method according to claim 2, characterized in that, In step S3, the method for removing the gold-plated polycarbonate film includes physical wiping and solvent dissolution.
9. The use of the micromotor of claim 1 in the preparation of a medicament for treating heart disease.
Citation Information
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