A magnetotactic nanomotor and its preparation method
By combining precious metal nanoparticles with magnetic nanoparticles, a magnetic nanomotor with controllable size and direction of motion is prepared, which solves the problems of small-size nanomotor preparation and direction of motion control, and achieves widespread application in the fields of biomedicine and micro-nano control.
Patent Information
- Application Number
- CN202111128855.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2021-09-26
- Publication Date
- 2025-06-13
- Estimated Expiration
- 2041-09-26
AI Technical Summary
Existing nanomotors have challenges in small size (<200nm) preparation and movement direction control, limiting their application in the fields of biomedical and micro-nano manipulation.
Precious metal nanoparticles are used as the basic motor framework, combining functional molecules and magnetic nanoparticles, and a controllable magnetic nanomotor with a size of 20-200nm is prepared by chemical synthesis.
Magnetic nanomotors with nanoscale size, good motion performance and controllable motion direction are achieved, and have a wide range of application prospects in the fields of biosensing and active drug delivery.
Smart Images
Figure CN113871119B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of the preparation of nano-devices, and particularly relates to a magnetotactic nano-motor and a preparation method thereof. Background Art
[0002] A nano-motor is a nano-device that can convert other forms of energy into kinetic energy and can move autonomously at the nano-scale. Currently, there are few reported preparation methods for nano-motors, and the preparation of small-sized nano-motors (<200 nm) faces greater challenges. In addition, due to the influence of Brownian motion and fluid perturbation, the control of the movement direction of small-sized nano-motors is also a major problem. The above problems greatly limit the application of nano-motors in the fields of biomedicine and micro-nano manipulation. Summary of the Invention
[0003] One of the purposes of the present invention is to provide a magnetotactic nano-motor, which has a small size, is of nano-scale size, has good movement performance and controllable movement direction, and has broad application prospects in the fields of biosensing and active drug delivery.
[0004] Another purpose of the present invention is to provide a preparation method of a magnetotactic nano-motor, which has a high qualified rate of the synthesized product, uniform particle size distribution, strong controllability, and can meet the preparation of nano-motors with different sizes and different materials.
[0005] The solution adopted by the present invention to achieve the first purpose is: a magnetotactic nano-motor, which uses noble metal nanoparticles as the basic skeleton of the motor, connects a functional molecule on one side and a magnetic nanoparticle on the other side.
[0006] Preferably, the noble metal nanoparticles are nano-gold.
[0007] Preferably, the functional molecule is polyethylene glycol, and the functional molecule is combined with the noble metal nanoparticles through a gold-thiol covalent bond.
[0008] Preferably, the magnetic nanoparticles are nano-ferroferric oxide or nano-ferric oxide, and the surface of the magnetic nanoparticles is modified with biotin.
[0009] Preferably, the particle size of the noble metal nanoparticles is 10–100 nm.
[0010] Preferably, the particle size of the magnetotactic nano-motor is 20–200 nm.
[0011] The solution adopted by the present invention to achieve the second purpose is: a preparation method of the magnetotactic nano-motor as described above, comprising the following steps:
[0012] (1) Prepare asymmetric noble metal-polystyrene eccentric particles by polymerizing noble metal nanoparticles and styrene monomers. In the asymmetric noble metal-polystyrene eccentric particles, polystyrene covers part of the surface of the noble metal nanoparticles, and the part of the noble metal nanoparticles not covered by polystyrene is the bare surface;
[0013] (2) Modify functional molecules on the bare surface of the noble metal nanoparticles of the asymmetric noble metal-polystyrene eccentric particles by using gold-thiol covalent bonds to obtain functional molecule-noble metal-polystyrene eccentric particles;
[0014] (3) Remove polystyrene from the functional molecule-noble metal-polystyrene eccentric particles obtained in step (2) to obtain functional molecule-noble metal eccentric particles. The part of the noble metal nanoparticles not connected to the functional molecules is the bare surface;
[0015] (4) Modify streptavidin on the bare surface of the functional molecule-noble metal eccentric particles in step (3) to obtain streptavidin-modified noble metal nanoparticles;
[0016] (5) Modify the surface of magnetic nanoparticles with biotin to obtain biotinylated magnetic nanoparticles;
[0017] (6) Assemble the biotinylated magnetic nanoparticles obtained in step (5) onto the surface of the streptavidin-modified noble metal nanoparticles obtained in step (4) to obtain the magnetotactic nanomotor.
[0018] Preferably, the specific process of step (4) is to modify biotinylated polyethylene glycol on the bare surface of the functional molecule-noble metal eccentric particles in step (3) by using gold-thiol covalent bonds, and then use the interaction between biotin and streptavidin to connect streptavidin to biotin, thereby modifying streptavidin on the bare surface of the noble metal nanoparticles.
[0019] Preferably, in step (1), the noble metal nanoparticles are prepared by the seed growth method.
[0020] Preferably, in step (5), the magnetic nanoparticles are prepared by the hydrothermal method.
[0021] The present invention synthesizes noble metal particles by chemical synthesis method, constructs an asymmetric structure with magnetic nanoparticles at the nanoscale, combines nanoscale noble metal particles with magnetic nanoparticles, and prepares magnetotactic nanomotors with a controllable size of 20-200 nm. The particles obtained by the chemical synthesis method have a high qualified rate and a uniform particle size distribution.
[0022] The magnetic nanoparticles of the present invention can react with external hydrogen peroxide to form a concentration gradient around the motor, resulting in enhanced diffusion; at the same time, they can sense the external magnetic field and generate a magnetic response, causing the motor to move directionally or change the movement speed of the motor. Specifically, the magnetic nanoparticles cause the motor to move directionally by responding to an external uniform magnetic field or a gradient magnetic field, and changing the magnitude of the gradient magnetic field can also change the movement speed of the motor. The magnetic field control direction is real-time, and the movement direction can be accurately controlled at the same time.
[0023] The present invention has the following advantages and beneficial effects:
[0024] 1. The magnetotactic nanomotor of the present invention has a small size, good biocompatibility, high sensitivity, good motion performance, and controllable motion direction, and has broad application prospects in the fields of sensing and environmental protection.
[0025] 2. The magnetotactic nanomotor of the present invention, due to the mechanical properties of the magnetic nanoparticles, can respond to the external magnetic field, and can accurately control the movement direction and speed in the gradient magnetic field, and can sense the change in the concentration of hydrogen peroxide in the solution in the uniform magnetic field to realize the regulation of the movement speed, and has excellent performance in direction control.
[0026] 3. The magnetotactic nanomotor of the present invention, due to the special optical and electrical properties of the noble metal nanoparticles, has excellent performance in the fields of biosensing and disease treatment.
[0027] 4. The preparation method of the present invention has strong controllability, the sizes of the noble metal nanoparticles and the magnetic nanoparticles are adjustable, and the accurate regulation of the particle size of the magnetotactic nanomotor can be realized. Magnetotactic nanomotors with a size of 20–200 nm can be formed to meet the needs of different applications and the preparation of nanomotors with different sizes and different materials.
[0028] 5. The preparation method of the present invention is suitable for the preparation of small-size nanomotors and has universality, providing possibilities for subsequent sensing and environmental protection. Brief Description of the Drawings
[0029] Figure 1 It is a schematic diagram of the structure and driving mechanism of the magnetotactic nanomotor in Example 1 of the present invention;
[0030] Figure 2 It is a transmission electron microscope image of 10–100 nm gold nanoparticles prepared in Example 1 of the present invention;
[0031] Figure 3 It is a transmission electron microscope image and element analysis diagram of the magnetotactic nanomotor prepared in Example 1 of the present invention;
[0032] Figure 4The trajectory diagrams of the magnetotactic nanomotors in hydrogen peroxide solutions with different concentrations, and the diagrams of the mean square displacement and diffusion coefficient varying with the urea concentration in Example 2 of the present invention;
[0033] Figure 5 The trajectory diagrams of the magnetotactic nanomotors in a gradient magnetic field, and the diagrams of the mean square displacement and diffusion coefficient varying with the magnetic field strength in Example 3 of the present invention;
[0034] Figure 6 The trajectory diagrams of the magnetotactic nanomotors in a uniform magnetic field, and the diagrams of the mean square displacement and diffusion coefficient varying with the hydrogen peroxide concentration in Example 4 of the present invention. Detailed implementation manners
[0035] To better understand the present invention, the following examples further illustrate the present invention, but the content of the present invention is not limited to the following examples only.
[0036] The schematic diagram of the structure and driving mechanism of the magnetotactic nanomotor of the present invention is as Figure 1 shown.
[0037] Example 1
[0038] The preparation of the magnetotactic nanomotor in this example mainly includes four parts: (1) the preparation of nanogolds with different sizes, (2) the preparation of gold-polystyrene eccentric nanoparticles, (3) the preparation of biotinylated iron oxide nanoparticles, and (4) the preparation of magnetotactic nanomotors.
[0039] (1) The preparation of nanogolds with different sizes: Synthesize 10-nm nanogolds (nanogold seeds with other particle sizes can also be synthesized according to needs in other examples): Take 1 mM chloroauric acid solution, stir and heat it in an oil bath until boiling, and then heat for another 10 min after boiling. Quickly add 38.8 mM sodium citrate aqueous solution, continue heating and reacting for 10 min, and then stop heating;
[0040] The primary growth of nanogolds: Take a certain amount of 10-nm nanogold seed solution, a certain amount of 60 mM sodium citrate solution and 142.5 mL of deionized water and add them into a three-necked flask. Heat and stir at 90 °C. After the system is stable, add a certain amount of 25 mM chloroauric acid solution in two portions. After 30 min, the primary growth of nanogolds is completed.
[0041] The subsequent growth of nanogolds: Take out about 1 / 3 of the sample solution, add an equal amount of deionized water to the original three-necked flask. After the temperature is stable, add a certain amount of 60 mM sodium citrate solution. After stabilization, add a certain amount of 25 mM chloroauric acid solution in two portions and react for 30 min. By controlling the number of growth times, nanogold particles with different sizes can be obtained.
[0042] (2) Preparation of asymmetric Au-PS eccentric particles: Add 1 mL of 50 mg / mL potassium persulfate solution, 1 mL of 6 mg / mL sodium 4-styrenesulfonate solution, 2.5 mL of water, and 16.5 mL of ethanol into a three-necked flask. After preheating at 70 °C for 10 minutes, then add 200 μL of the mixed solution (V styrene :V DVB = 200:1). After 2 minutes, add 3 mL of nano-gold, and continue the reaction for 4 hours. Centrifuge and collect to obtain asymmetric Au-PS eccentric particles. In this example, nano-gold with a particle size of 50 nm is selected for subsequent experimental operations. In other examples, nano-gold with other required particle sizes can also be selected for subsequent operations. The preparation methods of the magnetotactic nano-motors with different particle sizes of nano-gold are the same.
[0043] (3) Preparation of biotinylated magnetic iron oxide nanoparticles: Mix 15 mL of dibenzyl ether and 15 mL of oleylamine, add 1.0606 g of iron acetylacetonate, and heat the mixture for 3 h to obtain magnetic iron oxide nanoparticles. Add the magnetic iron oxide obtained by the hydrothermal method into 10 mL of dopamine aqueous solution (10 mg / mL); mix and oscillate the solution with 100 μL of 20 mg / mL Biotin-PEG-NHS (biotin-polyethylene glycol-N-hydroxysuccinimide) PB solution (10 mM, pH = 7.4), centrifuge and collect to obtain biotinylated magnetic iron oxide nanoparticles. (The preparation method of the biotinylated magnetic iron oxide nanoparticles in other examples is similar and will not be elaborated here.)
[0044] (4) Preparation of magnetotactic nano-motors: Disperse the obtained Au-PS particles in 6 mL of ultrapure water. Take 2 mL of the Au-PS solution, add 0.1 mL of HO-PEG-SH (hydroxy-polyethylene glycol-thiol) solution (10 mg / mL) and mix and oscillate; add 1 mL of N,N-dimethylformamide to the sample, disperse it in 500 μL of ultrapure water, add 100 μL of SH-PEG-Biotin (thiol-polyethylene glycol-biotin) solution (10 mg / mL), and after oscillation, disperse it in PB solution (10 mM, pH = 7.4). Take 100 μL of the above solution and add 100 μL of streptavidin solution (0.02 mg / mL), mix and disperse it in PB solution (10 mM, pH = 7.4). Take 100 μL of the above solution and add 100 μL of biotinylated magnetic iron oxide solution (0.075 mg / mL) and oscillate for reaction. After the reaction is completed, wash to obtain the magnetotactic nano-motors.
[0045] Figure 2 This is the transmission electron microscope image of 10–100 nm nano-gold prepared in the examples of the present invention, where Figure 2A, 2B, 2C, 2D, and 2E are the morphologies of 10nm, 30nm, 50nm, 70nm, and 100nm gold nanoparticles under a transmission electron microscope, and the scale bar is 50nm.
[0046] Figure 3 These are the transmission electron microscope images and elemental analysis diagrams of the magnetotactic nanomotors prepared in the examples of the present invention. Figure 3 A and 3B are the bright-field and dark-field images of the magnetotactic nanomotors in STEM mode of the transmission electron microscope respectively. Figure 3 C and D are the distributions of gold and iron elements under two-dimensional elemental analysis respectively. From the images, it can be seen that the magnetic beads are evenly distributed on one side of the motor, forming an asymmetric structure.
[0047] Example 2
[0048] The magnetotactic nanomotors prepared in Example 1 were placed in hydrogen peroxide solutions with concentrations of 0, 0.05, 0.1, 0.15, 0.2, 0.5, 0.75, and 1M respectively. Their movement trajectories are as shown in Figure 4 A, and their mean square displacement changes are as shown in Figure 4 B, and their diffusion coefficient changes are as shown in Figure 4 C. It can be seen from the figure that as the concentration of hydrogen peroxide increases, the moving distance of the motor gradually increases, and the slopes of the mean square displacement and the diffusion coefficient also gradually increase, and reach stability when the hydrogen peroxide concentration is 0.5M.
[0049] Example 3
[0050] The magnetotactic nanomotors prepared in Example 1 were placed in a 0.5M hydrogen peroxide solution, and their movement directions were observed in gradient magnetic fields of 1000, 600, 400, and 50Gs respectively. Their movement trajectories are as shown in Figure 5 A, and their mean square displacement changes are as shown in Figure 5 B, and their diffusion coefficient changes are as shown in Figure 5 C. It can be seen from the figure that as the gradient magnetic field strength increases, the moving distance of the motor gradually increases, and the slopes of the mean square displacement and the diffusion coefficient also gradually increase. At the same time, compared with Figure 4 it can be seen that the power provided by the external gradient magnetic field to the motor is much higher than the power generated by the chemical reaction of the motor.
[0051] Example 4
[0052] The magnetotactic nanomotors prepared in Example 1 were placed in hydrogen peroxide solutions with concentrations of 0, 0.2, 0.5, and 1M respectively, and their movement directions were observed in a uniform magnetic field. Their movement trajectories are as shown in Figure 6 A, and their mean square displacement changes are as shown in Figure 6 B, and their diffusion coefficient changes are as shown in Figure 6As shown in C, it can be seen from the figure that as the concentration of hydrogen peroxide increases, the moving distance of the motor gradually increases, and the slope of the mean square displacement and the diffusion coefficient also gradually increase, and reach stability when the hydrogen peroxide concentration is 0.5 M. At the same time, compared with Figure 4 it can be seen that in a uniform magnetic field, the movement speed of the magnetotactic nanomotor is only related to the fuel concentration and has nothing to do with the magnitude of the applied uniform magnetic field. The magnetic field only controls the direction of the motor.
[0053] All the raw materials listed in the present invention, as well as the upper and lower limits and interval values of the raw materials of the present invention, and the upper and lower limits and interval values of the process parameters (such as temperature, time, etc.) can implement the present invention, and the embodiments are not listed one by one here.
[0054] The above is the preferred implementation manner of the present invention. Of course, the scope of the rights of the present invention cannot be limited thereby. It should be pointed out that for those of ordinary skill in the art in this technical field, without departing from the principle of the present invention, several improvements and changes can be made, and these improvements and changes are also regarded as the protection scope of the present invention.
Claims
1. A magnetotactic nanomotor, characterized in that: using noble metal nanoparticles as the basic framework of the motor, with a functional molecule connected to one side and a magnetic nanoparticle connected to the other side. The noble metal nanoparticles and the magnetic nanoparticles construct an asymmetric structure at the nanoscale. The functional molecule is polyethylene glycol, and the functional molecule is combined with the noble metal nanoparticles through a gold-thiol covalent bond.
2. The magnetotactic nanomotor according to claim 1, characterized in that: The noble metal nanoparticles are gold nanoparticles.
3. The magnetotactic nanomotor according to claim 1, characterized in that: The magnetic nanoparticles are nano-ferroferric oxide or nano-ferric oxide, and the surface of the magnetic nanoparticles is modified with biotin.
4. The magnetotactic nanomotor according to claim 1, characterized in that: The particle size of the noble metal nanoparticles is 10–100 nm.
5. The magnetotactic nanomotor according to claim 1, characterized in that: The particle size of the magnetotactic nanomotor is 20–200 nm.
6. A preparation method of the magnetotactic nanomotor according to any one of claims 1–5, characterized in that it includes the following steps: (1) Prepare asymmetric noble metal-polystyrene eccentric particles by polymerizing noble metal nanoparticles and styrene monomers. In the asymmetric noble metal-polystyrene eccentric particles, polystyrene covers part of the surface of the noble metal nanoparticles, and the part of the noble metal nanoparticles not covered by polystyrene is the bare surface; (2) Modify the functional molecule on the bare surface of the noble metal nanoparticles of the asymmetric noble metal-polystyrene eccentric particles by using a gold-thiol covalent bond to obtain functional molecule-noble metal-polystyrene eccentric particles; (3) Remove the polystyrene from the functional molecule-noble metal-polystyrene eccentric particles obtained in step (2) to obtain functional molecule-noble metal eccentric particles. The part of the noble metal nanoparticles not connected to the functional molecule is the bare surface; (4) Modify streptavidin on the bare surface of the functional molecule-noble metal eccentric particles in step (3) to obtain streptavidin-modified noble metal nanoparticles; (5) Modify the surface of magnetic nanoparticles with biotin to obtain biotinylated magnetic nanoparticles; (6) Assemble the biotinylated magnetic nanoparticles obtained in step (5) onto the surface of the streptavidin-modified noble metal nanoparticles obtained in step (4) to obtain the magnetotactic nanomotor.
7. The preparation method of the magnetotactic nanomotor according to claim 6, characterized in that: The specific process of step (4) is to modify biotinylated polyethylene glycol on the bare surface of the functional molecule-noble metal eccentric particles in step (3) by using a gold-thiol covalent bond, and then use the interaction between biotin and streptavidin to connect streptavidin to biotin, thereby modifying streptavidin on the bare surface of the noble metal nanoparticles.
8. The preparation method of the magnetotactic nanomotor according to claim 6, characterized in that: In step (1), the noble metal nanoparticles are prepared by a seed growth method.
9. The preparation method of the magnetotactic nanomotor according to claim 6, characterized in that: In the step (5), the magnetic nanoparticles are prepared by a hydrothermal method.