Micron motor and preparation method and application thereof
Through the segmented tubular structure micromotor composed of Au and Zn elements, the concentration gradient of Zn elements drives movement, the efficiency and safety of micromotors in cardiac drug delivery in the prior art is solved, and a higher drug target is achieved The tropism and therapeutic effect demonstrate good biocompatibility and application prospects.
Patent Information
- Application Number
- CN202411326853.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-23
- Publication Date
- 2024-12-27
- Estimated Expiration
- 2044-09-23
AI Technical Summary
Existing micromotors have low drug delivery efficiency in targeted drug delivery, biocompatibility of drug carrier materials, insufficient control of drug release rate and duration, and lack of real-time monitoring and feedback mechanisms, limiting their use in cardiac drugs. Application.
A segmented tubular structure micromotor consisting of Au and Zn elements is driven by the concentration gradient of Zn elements, combining simple preparation methods and high biosafety to improve the targeting and therapeutic effect of the drug.
Longer drug exercise time and higher cellular targeting are achieved, improved therapeutic effect, and shown good biocompatibility and safety, suitable as a means of mechanical or chemical stimulation of cardiac drugs.
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Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of micrometer motors, and in particular to a micrometer motor and a preparation method and application thereof. Background Art
[0002] The heart is an important organ in the human body. The heartbeat transports blood to all parts of the body, allowing cells to maintain normal metabolism and function. The sinoatrial node, also known as the sinus node, is the pacemaker of the heart under normal conditions. When this node fails, an artificial electric pacemaker is often implanted to stimulate the heart to restore normal heart rate. However, electric pacemakers are powered by electrochemical batteries, which results in a limited service life and are prone to electrode failure or interference from external electromagnetic fields.
[0003] A micromotor is a micrometer-scale power device that can convert external environmental energy into its own kinetic energy. It has broad application prospects in the fields of targeted drug delivery, precision medicine, biosensing, and environmental remediation. The micromotor itself is small in size and can follow the blood flow, and by adjusting its size, its distribution in various organs can be affected. If micromotors can be used as mechanical or chemical myocardial stimulants for cardiac drugs, surgical trauma can be avoided, treatment effects can be improved, and side effects can be reduced.
[0004] Existing micromotors still have the following defects in targeted drug delivery: (1) The drug delivery efficiency is low, making it difficult to achieve precise targeting, resulting in unstable treatment effects and increased risk of side effects; (2) Drug carrier materials have biocompatibility and safety issues, which may cause immune responses or other adverse reactions; (3) Traditional drug delivery systems have insufficient control over drug release rate and duration, affecting the therapeutic effect; (4) Drug carriers have poor durability and stability in the complex environment of the body, which may lead to drug degradation or inactivation; in addition, there is still a lack of effective real-time monitoring and feedback mechanisms, which makes it difficult to accurately evaluate the distribution and effects of drugs after they enter the body, making it impossible to adjust treatment plans in a timely manner, greatly limiting the application of micromotors in cardiac drugs. Summary of the invention
[0005] The present invention aims to solve at least one of the above-mentioned technical problems existing in the prior art. To this end, one of the purposes of the present invention is to provide a micro motor; the second purpose of the present invention is to provide a method for preparing such a micro motor; the third purpose of the present invention is to provide an application of such a micro motor.
[0006] In order to achieve the above object, the technical solution adopted by the present invention is:
[0007] A first aspect of the present invention provides a micro-motor, wherein the element composition of the micro-motor includes Au and Zn; the mass ratio of the Au element to the Zn element is 1:(3-5).
[0008] Preferably, the mass ratio of the Au element to the Zn element is 1:(3-4).
[0009] Preferably, the micromotor is composed of Au element and Zn element; the mass ratio of the Au element to the Zn element is 1:(3-4).
[0010] Preferably, the micro-motor has a segmented tubular structure.
[0011] Preferably, the length of the micro-motor is 1-8 μm; further preferably, the length of the micro-motor is 3-6 μm.
[0012] Preferably, the diameter (outer diameter) of the circular cross section of the micro motor is 100-400 nm; further preferably, the diameter (outer diameter) of the circular cross section of the micro motor is 200-250 nm.
[0013] Preferably, the segmented tubular structure micro-motor comprises a stabilizing segment and a driving segment; the Au element is enriched in the stabilizing segment (Au segment); and the Zn element is enriched in the driving segment (Zn segment).
[0014] Preferably, the length of the stabilizing segment is 1-2 μm; further preferably, the length of the stabilizing segment is 1-1.5 μm.
[0015] Preferably, the length of the driving segment is 2-4 μm; further preferably, the length of the driving segment is 2-2.5 μm.
[0016] Preferably, there is a clear dividing line between the stabilizing section and the driving section.
[0017] Specifically, the micromotor provided by the present invention is composed of Au and Zn elements, with the content of Zn element being dominant, and is an Au / Zn composite micromotor. The Au element and the Zn element are respectively enriched at the two ends, forming a stable section (Au section) and a driving section (Zn section) with a clear dividing line. In the Zn section, Zn is oxidized to Zn 2+ , with Zn 2+ Slowly accumulating, eventually forming a concentration gradient in the Zn segment, prompting the motor to move. The micro motor provided by the present invention is driven by the Zn segment concentration gradient, and the higher Zn element content and longer driving segment (Zn segment) length can provide the micro motor with a longer movement time.
[0018] Preferably, the average speed of the micro-motor moving in deionized water is 3-8 μm / s; further preferably, the average speed of the micro-motor moving in deionized water is 4-6 μm / s.
[0019] Preferably, the range of movement of the micromotor in deionized water is (15-30)×(15-30) μm. 2 ; Further preferably, the range of movement 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; further preferably, the Zeta potential of the micromotor is -23 to -19 mV.
[0021] The second aspect of the present invention provides a method for preparing the micromotor according to the first aspect of the present invention, comprising the following steps:
[0022] S1, evaporating a gold nanolayer on the surface of a polycarbonate film having a hole structure to obtain a gold-plated polycarbonate film;
[0023] S2, using the gold-plated polycarbonate film as a working electrode, sequentially electrochemically depositing Au and Zn;
[0024] S3, removing the gold-plated polycarbonate film to obtain the micro-motor.
[0025] Preferably, in step S1, the pore size of the polycarbonate film is 300-450 nm; further 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; further preferably, the pore length of the polycarbonate film is 12-15 mm.
[0027] Preferably, in step S1, the thickness of the gold layer of the gold-plated polycarbonate film is 150-250 nm; further preferably, the thickness of the gold layer of the gold-plated polycarbonate film is 170-220 nm.
[0028] Preferably, in the step S1, the vapor deposition is performed in a vacuum evaporation deposition machine.
[0029] Preferably, in the step S1, the specific operation of the evaporation is: fixing the polycarbonate film on the substrate, placing it in an evaporation chamber, placing gold particles in an evaporation tank, and performing evaporation after evacuating the chamber.
[0030] Preferably, the amount of gold used is 0.5-1.5 g; more preferably, the amount of gold used is 0.7-1.2 g.
[0031] Preferably, the vacuum degree of the cavity is ≤1×10 -4 Pa after the start of evaporation.
[0032] Preferably, in step S1, the evaporation procedure of the gold nanolayer is: first The rate of evaporation of 15-50nm thick gold layer; The evaporation process of the gold nanolayer is as follows: The rate of evaporation of 15-30nm thick gold layer; Continue evaporation at a rate of 150-250nm.
[0033] Specifically, the gold nanolayer is deposited by a programmed acceleration evaporation method, so that the gold nanolayer and the polycarbonate film can be attached more closely.
[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 the step S2, when Au is electrochemically deposited, the electroplating solution contains sodium gold sulfite; further preferably, the electroplating solution contains sodium gold sulfite.
[0036] Preferably, in the step S2, when Au is electrochemically deposited, the deposition voltage is -0.5-1.5V; further preferably, the deposition voltage is -0.8-1.2V.
[0037] Preferably, in the step S2, when Au is electrochemically deposited, the deposition time is 5-15 min; further preferably, the deposition time is 7-12 min.
[0038] Preferably, in the step S2, when electrochemically depositing Zn, the plating solution is a mixture of Zn salt and H3BO3.
[0039] Preferably, the Zn salt comprises ZnSO4·7H2O.
[0040] Preferably, in the mixed solution of Zn salt and H3BO3, the initial concentration ratio of the Zn salt to H3BO3 is (1-3):1; further preferably, the initial concentration ratio of the Zn salt to H3BO3 is (1.5-2.5):1.
[0041] Preferably, the amount of the Zn salt and H3BO3 mixed solution used is 40-60 mL; further preferably, the amount of the Zn salt and H3BO3 mixed solution used is 45-55 mL.
[0042] Preferably, in the step S2, when electrochemically depositing Zn, the deposition voltage is -2 to -1V; further preferably, the deposition voltage is -1.5 to -1V.
[0043] Preferably, in the step S2, when the Zn is electrochemically deposited, the deposition time is 5-15 min; further preferably, the deposition time is 7-12 min.
[0044] Preferably, the specific operation of the electrochemical deposition of Au and Zn is: placing the gold-plated polycarbonate film into an electrochemical deposition bracket, connecting the electrochemical workstation, pouring the gold plating solution to completely immerse the electrochemical deposition bracket, depositing Au, and rinsing the electrode with deionized water; pouring the electroplating solution, depositing Zn, and removing the gold-plated polycarbonate film on which Au and Zn are deposited from the electrochemical deposition bracket to obtain the micromotor.
[0045] Preferably, in step S3, the method of removing the gold-plated polycarbonate film includes physical erasing and solution dissolution.
[0046] Preferably, the physical erasing comprises grinding the gold-coated polycarbonate film on frosted glass to remove the nano-gold layer.
[0047] Preferably, the solution dissolving includes adding a solution to dissolve the polycarbonate film.
[0048] Preferably, the solution comprises at least one of dichloromethane and tetrahydrofuran.
[0049] Preferably, in the step S3, after removing the gold-plated polycarbonate film, the step further includes washing the micro-motor.
[0050] Preferably, the washing reagents include ethanol and deionized water.
[0051] The third aspect of the present invention provides the use of the micromotor described in the first aspect of the present invention in cardiac medicine.
[0052] Compared with the prior art, the present invention has the following beneficial effects:
[0053] 1) The micromotor provided by the present invention includes Au and Zn elements, wherein the content of Zn element is dominant. The micromotor has a segmented tubular structure with obvious dividing lines between segments. A higher content of Zn element is enriched to form a Zn segment, and the concentration gradient is used to make the Zn segment serve as a driving segment to drive the motor to move. A higher Zn element content and a longer driving segment (Zn segment) length can provide the micromotor with a longer movement time, and the Au segment improves the cell targeting of the motor.
[0054] 2) The micromotor preparation method provided by the present invention is simple, has mild process conditions, and is suitable for industrial use.
[0055] 3) The micromotor provided by the present invention has high biological safety and can effectively stimulate mouse cardiomyocytes to make Ca 2+The concentration increased, indicating that it has good application prospects as a cardiac drug. BRIEF DESCRIPTION OF THE DRAWINGS
[0056] Figure 1 This is a cold field emission electron microscope scanning electron microscope image of the Au / Zn composite micromotor of the embodiment;
[0057] Figure 2 Element distribution diagram of the Au / Zn composite micromotor of the embodiment;
[0058] Figure 3 Element spectrum of the Au / Zn composite micromotor in the embodiment;
[0059] Figure 4 A statistical analysis chart of the length and diameter of the Au / Zn composite micro-motor of the embodiment;
[0060] Figure 5 is the Zeta potential diagram of the Au / Zn composite micromotor of the embodiment;
[0061] Figure 6 This is a motion performance analysis diagram of the Au / Zn composite micromotor in deionized water;
[0062] Figure 7 This is a Calcein-AM / PI staining image of the co-culture experiment of Au / Zn composite micromotor and mouse cardiomyocytes in Example;
[0063] Figure 8 The cell survival rate in the co-culture experiment of Au / Zn composite micromotor and mouse cardiomyocytes in Example;
[0064] Fig. 9 After adding the Au / Zn composite micromotor to mouse myocardial cells, Ca 2 + Fluorescence intensity change diagram;
[0065] Fig.10 Mouse cardiomyocyte Ca 2+ Plot of mean fluorescence intensity versus time. DETAILED DESCRIPTION
[0066] The present invention is further described in detail below by specific examples. The raw materials, reagents or devices used in the examples can be obtained from conventional commercial sources or by prior art methods unless otherwise specified. Unless otherwise specified, the experiments or test methods are conventional methods in the art.
[0067] The raw material information used in the examples is shown in Table 1:
[0068] Table 1 Raw material information table used in the examples
[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 Shenlan 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 Shanghai BioTech Biotech Co., Ltd. Propidium iodide (PI) Shanghai BioTech Biotech Co., Ltd. Fetal bovine serum (FBS) Shanghai BioTech Biotech Co., Ltd. Dual Antibody Shanghai BioTech Biotech Co., Ltd. Glutamine Thermo Fisher Trypsin-EDTA solution Shanghai BioTech Biotech Co., Ltd. MEM medium Thermo Fisher Mouse cardiomyocytes (HL-1) Shanghai BioTech Biotech Co., Ltd.
[0070] Example
[0071] This embodiment provides an Au / Zn composite micro-motor, which is composed of Au element and Zn element, and the mass ratio of Au element to Zn element is 1:4. The preparation steps are as follows:
[0072] S11. Fix the polycarbonate film (400nm, 13mm) on the substrate, and then put it into the evaporation chamber of the vacuum evaporation deposition machine. Put 1g of gold particles into the evaporation tank and wait for the chamber to be evacuated. When the vacuum degree in the chamber is ≤1×10 -4 Pa, start evaporation. A 20 nm thick gold layer was deposited at a rate of 1000 nm, and then the deposition rate was increased to After forming a 200 nm gold nanolayer by evaporation, the evaporation was stopped to obtain a gold-coated polycarbonate film, which was used as a template for preparing micromotors.
[0073] S21. Prepare a micro motor by electrochemical deposition using a three-electrode system, wherein 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. Place the gold-plated polycarbonate film in an electroplating support, connect the electrochemical workstation, pour the gold plating solution to completely immerse the electroplating support, deposit at a constant voltage of -0.9V for 10 minutes, then take it out, and rinse the electrode with deionized water; use deionized water as a solvent, prepare 50mL of a mixed solution of 0.2mol / L ZnSO4·7H2O and 0.1mol / L H3BO3 as a zinc plating solution, deposit at a constant voltage of -1.230V for 10 minutes, then take it out, and take out the gold-plated polycarbonate film deposited with Au and Zn from the electroplating support.
[0074] S31. Grind the gold-plated polycarbonate film on which Au and Zn were deposited on frosted glass to remove the nano-gold layer (apply appropriate pressure to avoid damage to the structure of the motor, rinse with deionized water several times during the process, and stop grinding after the gold material is completely ground), add CH2Cl2 to dissolve the polycarbonate film to release the micro-motor. Use ultrasonic centrifugation to wash the solution twice with ethanol and deionized water, and finally obtain the Au / Zn composite micro-motor dispersed in deionized water.
[0075] Material Characterization and Performance Testing
[0076] 1. Structure and morphology characterization of Au / Zn composite micromotor:
[0077] (1) The Au / Zn composite micro-motor in the embodiment was added to deionized water for ultrasonic dispersion, 10 μL of the solution was coated on the silicon wafer of the conductive glue on the sample stage, and placed in a vacuum oven for drying at 50°C for 3 h. ① The morphology of the Au / Zn composite micro-motor was observed using a cold field emission electron microscope (S-4800, Hitachi, Japan); ② The elemental analysis of the Au / Zn composite micro-motor was performed using an energy dispersive X-ray spectrometer (EDX), with an acceleration voltage of 10 kV and a probe working distance of 8 mm; ③ The length and diameter of 30 Au / Zn composite micro-motors were statistically analyzed using ImageJ software.
[0078] Figure 1 This is a cold field emission electron microscope scanning electron microscope image of the Au / Zn composite micromotor in the embodiment. Figure 1 It can be seen that the Au / Zn composite micro-motor prepared in the embodiment has a segmented tubular structure with a relatively regular shape and obvious dividing lines between the segments.
[0079] Figure 2 Element distribution diagram of the Au / Zn composite micromotor of the embodiment, wherein: Figure 2 (a) is the comprehensive element response diagram, Figure 2 (b) is the Au element response diagram, Figure 2 (c) is the Zn element response diagram; Figure 3 The element spectrum of the Au / Zn composite micromotor in the embodiment. Figure 2 and Figure 3 It can be seen that the Au / Zn composite micromotor prepared in the embodiment is composed of Au and Zn elements, the content of Zn element is greater than that of Au element, and the content of Zn element is dominant, and the mass ratio of Zn element to Au element is close to (3-4): 1. In the segmented tubular structure, the Zn segment is longer, and the Zn segment is the driving segment. The higher Zn element content and the longer driving segment (Zn segment) length are conducive to providing the micromotor with a longer movement time.
[0080] Figure 4 The length and diameter of the Au / Zn composite micromotor in the embodiment are statistically analyzed, wherein: Figure 4 (a) is the length statistical analysis chart, Figure 4 (b) is the diameter statistical analysis chart. Figure 4It can be seen that the length distribution range of the Au / Zn composite micro-motor prepared in the embodiment is 1-8μm, mainly concentrated in 3-6μm; the circular cross-sectional diameter (outer diameter) distribution range of the Au / Zn composite micro-motor is 100-400nm, mainly concentrated in 200-250nm. The size distribution range of the Au / Zn composite micro-motor is relatively wide, and the size of the micro-motor template can be adjusted by adjusting the pore size and length of the polycarbonate film during the preparation process, thereby controlling the size of the micro-motor and affecting its distribution in the body or other environments.
[0081] (2) The Au / Zn composite micromotors were ultrasonically dispersed in deionized water, added to a sample cell, and the zeta potential of the Au / Zn composite micromotors was measured using a Malvern particle size analyzer.
[0082] Figure 5 The Zeta potential diagram of the Au / Zn composite micromotor in the embodiment is shown in FIG. Figure 5 It can be seen that the Zeta potential of the Au / Zn composite micromotor prepared in the embodiment is -19.73mV, and 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 agglomeration of the micromotors and has good dispersion stability.
[0083] 2. Analysis of the motion performance of Au / Zn composite micro-motor:
[0084] The Au / Zn composite micromotor in the embodiment was added to deionized water for ultrasonic dispersion, and the movement of the micromotor in deionized water was observed under an inverted fluorescence microscope (NikonTi2-A, Nikon Corporation) and a video was recorded, with a frame rate of 10 frames per second. Ten micromotors in the video were selected, and the manual sampling function of Image J was used to analyze the movement path of the micromotor within 10 seconds. The movement trajectory of the micromotor was normalized using the Chemotaxis tool, the length of the motor's movement trajectory was analyzed, and the movement speed of the motor was calculated.
[0085] Figure 6 The motion performance analysis diagram of the Au / Zn composite micromotor in deionized water is shown in the following figure. Figure 6 It can be seen that the average movement speed of the Au / Zn composite micromotor in deionized water is 4.51 μm / s, and the directionality is 0.11; the movement path of the micromotor is elliptical and can be relatively stable within a range of 20×20 μm. 2 This suggests that a single micromotor can exert sustained effects on cells within this range.
[0086] 3. Biocompatibility test of Au / Zn composite micromotor:
[0087] The Au / Zn composite micromotor of the embodiment was co-cultured with mouse cardiomyocytes (HL-1), and the cell survival was detected by fluorescence staining to evaluate the biocompatibility of the Au / Zn composite micromotor. 5000 cells were inoculated in each of nine culture dishes and cultured in an incubator at 37°C and 5% CO2 for 72 hours. Then, 10 μL of Au / Zn composite micromotor dispersed in PBS buffer was added to each culture dish, shaken to disperse it evenly, and then continued to be cultured in a constant temperature box. The cell survival was detected by fluorescence staining at 0h, 24h, and 48h. The specific operation was: pour out the cell culture solution, add a mixed solution of Calcein-AM and PI, place the culture dish in a constant temperature box for incubation for 30 minutes, and observe under an inverted fluorescence microscope.
[0088] Figure 7 The Calcein-AM / PI staining diagram of the co-culture experiment of Au / Zn composite micromotor and mouse cardiomyocytes in the embodiment, wherein the scale of the Calcein-AM / PI staining diagram is 100 μm, from left to right are the bright field, fluorescein isothiocyanate labeled fluorescence field (FITC fluorescence field), Texas Red labeled fluorescence field (Texas Red fluorescence field) and merged diagram (Merge diagram), and from top to bottom are the time of detecting cell survival (0h, 24h and 48h). Figure 7 It can be seen that in the bright field, the mouse cardiomyocytes are spindle-shaped, indicating that the cardiomyocytes are well attached to the wall, and several Au / Zn composite micromotors fall near the cells; FITC fluorescence field, Texas Red fluorescence field and Merge image show that within 1-48 hours, most of the cells are in a viable state.
[0089] Figure 8 The cell survival rate in the co-culture experiment of Au / Zn composite micromotor and mouse cardiomyocytes is shown in the example. Figure 8 It can be seen that the survival rate of mouse cardiomyocytes (HL-1) at the initial stage of culture (0h) is 99.53%, the survival rate at the 24th hour of co-culture is 98.14%, and the survival rate at the 48th hour of co-culture is 96.89%. The survival rates within 0-48h are all high, and the survival rate of cardiomyocytes near the micromotor is 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 stimulates mouse cardiomyocytes experiment:
[0091] 1) Culture of mouse cardiomyocytes (HL-1): MEM medium was used to culture mouse cardiomyocytes (HL-1), and 10% fetal bovine serum, 1% double antibody and 1% glutamine were added to the MEM medium. The culture flask was placed in a constant temperature incubator at 37°C and 5% CO2 for culture, and observed under an optical microscope every 2 days. The culture medium was replaced: the waste liquid was discarded, the cells were washed with PBS buffer, and then the above-prepared complete culture medium was added. When the cell density reached 80%, the cells were digested with digestive solution (trypsin-EDTA solution), and the cells were centrifuged at a speed of 1000r / min for 4min. The cells were resuspended with complete culture medium and then passaged: the cell suspension was inoculated into a culture dish for subsequent experiments, and the cells were then divided into culture flasks for standby use.
[0092] 2) Au / Zn composite micromotors stimulate mouse cardiomyocytes (HL-1): remove MEM cell culture medium, wash cells with PBS buffer, add PBS buffer and Ca 2+ Fluorescent dye was added and the cells were stained by incubating at 37°C for 30 min in a cell culture incubator. The fluorescent dye solution was removed, the cells were washed with glucose solution, 1 mL of glucose solution was added, and the cells were placed on an inverted fluorescence microscope for observation. 5 μL of Au / Zn composite micromotors (dispersed in glucose solution) were added, and the cell images were observed and recorded. The cell images after the Au / Zn composite micromotors were added were used to observe Ca using the FITC channel. 2+ The fluorescence images were analyzed by ImageJ software to determine the changes in fluorescence dye reaction over time.
[0093] Fig. 9 After adding the Au / Zn composite micromotor to mouse myocardial cells, Ca 2+ Fluorescence intensity change diagram, Fig.10 Mouse cardiomyocyte Ca 2+ The average fluorescence intensity changes over time. Fig. 9 and Fig.10 It can be seen that after the Au / Zn composite micromotor of the embodiment was added to the cell solution, the Ca 2+ The fluorescence intensity of Ca increased gradually and reached the highest value at 30s. Then, due to fluorescence quenching, the fluorescence intensity gradually weakened. However, at 285s, the fluorescence intensity of Ca 2+ The fluorescence intensity is still higher than that at 0s. 2+ The concentration of Ca 2 The fluorescence intensity of + increased, indicating that Ca 2+ The concentration increases.
[0094] In the process of myocardial cell excitation-contraction coupling, myocardial cells first generate action potentials, followed by L-type Ca2+ on the T-tubules of myocardial cells. 2+ Channels (L-type Ca2+ channels) open, and extracellular Ca 2+ influx, influx of Ca 2+ Some of them bind to the calcium release channel Ryanodine receptor (RyR) present in the endoplasmic reticulum / sarcoplasmic reticulum, releasing Ca in the sarcoplasmic reticulum. 2+ , so that the cytoplasmic Ca 2+ As the concentration increases, Ca 2+ It binds to troponin, triggering the cross bridges on the thick filaments to bind to the thin filaments and slide, thereby causing contraction. 2+ Increased concentrations mean that intracellular Ca 2+ 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, Ca 2+ The increase in concentration is usually associated with contraction, which plays a vital role in heartbeat. The Au / Zn composite micromotor provided by the present invention has good biosafety and can effectively stimulate mouse cardiomyocytes to make Ca 2+ The concentration increased, indicating that it has good application prospects as a cardiac drug.
Claims
1. A micrometer motor, characterized in that: The element composition of the micromotor includes Au and Zn; the mass ratio of the Au element to the Zn element is 1:(3-5).
2. The micromotor according to claim 1, characterized in that: The micro-motor has a segmented tubular structure; And / or, the length of the micromotor is 1-8 μm; And / or, the circular cross-section diameter of the micromotor is 100-400 nm.
3. The micromotor according to claim 2, characterized in that: The segmented tubular structure micro-motor includes a stabilizing segment and a driving segment; the Au element is enriched in the stabilizing segment; and the Zn element is enriched in the driving segment.
4. The micromotor according to claim 3, characterized in that: The length of the stabilizing segment is 1-2 μm; And / or, the length of the driving segment is 2-4 μm.
5. The method for preparing a micromotor according to any one of claims 1 to 4, characterized in that: The following steps are involved: S1, evaporating a gold nanolayer on the surface of a polycarbonate film having a hole structure to obtain a gold-plated polycarbonate film; S2, using the gold-plated polycarbonate film as a working electrode, sequentially electrochemically depositing Au and Zn; S3, removing the gold-plated polycarbonate film to obtain the micro-motor.
6. The preparation method according to claim 5, characterized in that: In the step S1, the pore size of the polycarbonate film is 300-450 nm; And / or, the evaporation procedure of the gold nanolayer is: first The rate of evaporation of 15-50nm thick gold layer; Continue evaporation at a rate of 150-250nm.
7. The preparation method according to claim 5, characterized in that: In the 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.
8. The preparation method according to claim 5, characterized in that: In the step S2, when Au is electrochemically deposited, the electroplating solution contains gold sulfite; the deposition voltage is -0.5-1.5V; and the deposition time is 5-15min; And / or, 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 to 15min.
9. The preparation method according to claim 5, characterized in that: In the step S3, the method of removing the gold-plated polycarbonate film includes physical erasing and solvent dissolution.
10. Use of the micromotor according to any one of claims 1 to 4 in cardiac medicine.
Citation Information
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