Magnetic microrobot and preparation method and application thereof

Abstract

The application discloses a magnetic micro robot and a preparation method and application thereof, and belongs to the technical field of medical devices. The magnetic micro robot provided by the application comprises a gel base body and nano magnetic particles dispersed in the gel base body; and the phase transition temperature of the gel base body is 38.5-40 DEG C. The magnetic micro robot provided by the application has obvious advantages in long-distance targeting and short-distance targeting delivery processes. The application further provides a preparation method and application of the magnetic micro robot.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and in particular to a magnetic microrobot, its preparation method, and its application. Background Technology

[0002] Microrobots are miniature structures ranging in size from micrometers to nanometers, capable of converting magnetic, chemical, or light energy into kinetic energy to drive their own movement. Magnetic fields have strong penetrability, and low-intensity magnetic fields are non-toxic to the human body; therefore, magnetic microrobots have proven to have broad application prospects in drug delivery. Compared to traditional passive diffusion or bloodstream drug delivery systems, magnetic micro / nano robots can move to the lesion area under the drive and control of an external magnetic field, increasing the drug concentration at the target site and achieving targeted therapy.

[0003] The process of drug delivery using micro- and nanorobots can be divided into long-distance targeting (from the injection site to the vicinity of the target area) and short-distance targeting (from the vicinity of the target area to deep into the target tissue). For microrobots at the micrometer or even larger scale, their larger size typically grants them superior mobility, imaging clarity, and greater drug loading capacity. These properties give them an advantage in long-distance targeting. However, similarly limited by their size, microrobots have weaker short-distance targeting capabilities, struggling to approach the target area through narrow channels. For example, in drug delivery to tumor tissue, after a microrobot approaches the tumor and releases the drug, the drug typically only diffuses freely around the target, with most of it failing to penetrate deep into the tissue, thus affecting treatment efficiency. For nanoscale magnetic nanorobots, to ensure their magnetic control performance, drugs and functional two-dimensional materials are usually mounted on the surface of magnetic particles through surface modification. They possess strong short-distance targeting capabilities. However, nanorobots are prone to loss during long-distance transport, and the drug loading capacity of a single nanorobot is relatively small.

[0004] In summary, existing micro- and nano-robots are unable to simultaneously achieve both long-range and short-range targeting. Summary of the Invention

[0005] This invention aims to at least solve one of the technical problems existing in the prior art. To this end, this invention proposes a magnetic microrobot that has significant advantages in both long-distance and short-distance targeted delivery processes.

[0006] The present invention also provides a method for preparing the above-mentioned magnetic microrobot.

[0007] The present invention also provides a targeted drug for preparation of raw materials including the above-mentioned magnetic microrobot.

[0008] According to an embodiment of a first aspect of the present invention, a magnetic microrobot is provided, the magnetic microrobot comprising a gel matrix and nanomagnetic particles dispersed in the gel matrix; The phase transition temperature of the gel matrix is ​​38.5~40℃.

[0009] Wherein, the phase transition temperature means that below the phase transition temperature, the gel matrix exists in a gel state, and above the phase transition temperature, the gel structure of the gel matrix collapses to form a liquid state.

[0010] The magnetic microrobot according to embodiments of the present invention has at least the following beneficial effects: The magnetic microrobot provided by this invention contains nano-magnetic particles, thus possessing the ability to roll under the drive of an external magnetic field, and the ability to cause the surrounding environment to heat up under the stimulation of near-infrared light or high-frequency alternating magnetic field.

[0011] By limiting the phase transition temperature of the gel matrix and considering the presence of nanomagnetic particles, it can be seen that the magnetic microrobot provided by this invention can disintegrate under near-infrared light or alternating magnetic field stimulation, releasing nanomagnetic particles. These nanomagnetic particles have a small particle size and can continue to aggregate under the drive of an external magnetic field. Therefore, the magnetic microrobot provided by this invention possesses excellent long-range targeting capabilities before disintegration and, if necessary, excellent drug loading capacity; after disintegration, it exhibits excellent short-range targeting capabilities.

[0012] According to some embodiments of the present invention, the phase transition temperature of the gel matrix is ​​38.5~40℃. For example, it can be 38.5℃, 38.8℃, 39℃, 39.2℃, 39.4℃, 39.5℃, 39.6℃, 39.8℃, 40℃; or a range of values ​​consisting of any two of the above points.

[0013] According to some embodiments of the present invention, the gel matrix is ​​a mixture of polyvinyl alcohol, gelatin and sodium alginate.

[0014] According to some embodiments of the present invention, the mass ratio of polyvinyl alcohol, gelatin, and sodium alginate is 10:5 to 10:0.5 to 1. Specifically, it can be 10:5:0.5, 10:5:0.8, 10:5:1, 10:10:0.5, 10:10:0.8, 10:10:1, 10:8:0.5, 10:8:0.8, 10:8:1; or a range of values ​​consisting of any two of the above points.

[0015] According to some embodiments of the present invention, the Bloom value of the gelatin is 280 to 340. For example, it can specifically be 280, 300, 320, 340; or a range of values ​​consisting of any two of the above points.

[0016] According to some embodiments of the present invention, the particle size of the nanomagnetic particles is 200~800nm.

[0017] According to some embodiments of the present invention, the nanomagnetic particles comprise iron oxide powder.

[0018] According to some embodiments of the present invention, the magnetic microrobot further includes a drug dispersed in the gel matrix. When the ambient temperature reaches the phase transition temperature of the gel matrix, both the drug and the nanomagnetic particles are released and deeply targeted.

[0019] According to some embodiments of the present invention, the magnetic microrobot has a spherical or near-spherical morphology.

[0020] According to some embodiments of the present invention, the particle size of the magnetic microrobot is 0.5~4mm.

[0021] According to some embodiments of the present invention, the magnetic microrobot exhibits photothermal effects. Specifically, its temperature increases after irradiation with infrared light. The intensity of infrared light is 1~2 W / cm² 2 For example, it could be 1W / cm². 2 1.5W / cm 2 2W / cm 2 ; or the range of values ​​formed by any two of the above point values.

[0022] The time required to heat to the phase transition point of the gel matrix is ​​≤75s.

[0023] According to some embodiments of the present invention, the magnetic microrobot exhibits a magnetocaloric effect. Specifically, its temperature increases in a high-frequency alternating magnetic field. The frequency of the high-frequency alternating magnetic field is 450~550kHz. For example, 500kHz.

[0024] According to some embodiments of the present invention, the magnetic microrobot moves in a directional manner under the influence of an external magnetic field. The external magnetic field is an alternating magnetic field (also called a rotating magnetic field); the frequency of the external magnetic field is 1~20Hz. Specifically, it can be 1Hz, 2Hz, 3Hz, 4Hz, 5Hz, 6Hz, 7Hz, 8Hz, 9Hz, 10Hz, 11Hz, 12Hz, 13Hz, 14Hz, 15Hz, 16Hz, 17Hz, 18Hz, 19Hz, 20Hz; or a range of any two of the above values. This magnetic field is significantly lower than the high-frequency alternating magnetic field that would cause the magnetic microrobot to heat up; therefore, the magnetic microrobot will not significantly heat up or disintegrate during its directional movement.

[0025] According to an embodiment of a second aspect of the present invention, a method for fabricating the magnetic microrobot described in the first aspect of the present invention is provided, the method comprising the following steps: S1. Prepare a mixed aqueous solution, wherein the mixed aqueous solution includes components of the gel matrix; S2. Mix the nano-magnetic particles and the aqueous solution; S3. Add the mixture obtained in step S2 to the mineral oil and cool it down.

[0026] Since the preparation method adopts all the technical solutions of the magnetic microrobots in the above embodiments, it has at least all the beneficial effects brought about by the technical solutions in the above embodiments.

[0027] According to some embodiments of the present invention, in step S1, the preparation process of the mixed aqueous solution includes first preparing an aqueous solution of PVA, and then mixing the aqueous solution of PVA, gelatin, sodium alginate, and the remaining water. The preparation temperature of the PVA aqueous solution is 90°C; in actual production, this temperature is not strictly limited, as long as it can fully dissolve the PVA, but to save energy, the present invention uses a temperature around 90°C. The mixing temperature of the PVA aqueous solution, gelatin, sodium alginate, and the remaining water is 55~65°C; this ensures the full dissolution and mixing of all components.

[0028] According to some embodiments of the present invention, in step S1, the mass concentration of sodium alginate in the mixed aqueous solution is 0.5-1%. For example, it can be 0.5%, 0.8%, 1%; or a range of values ​​composed of any two of the above points.

[0029] According to some embodiments of the present invention, the concentration of the nanomagnetic particles in the mixture obtained in step S2 is 0.3 g / mL to 0.6 g / mL. For example, it can specifically be 0.3 g / mL, 0.35 g / mL, 0.4 g / mL, 0.45 g / mL, 0.5 g / mL, 0.55 g / mL, 0.6 g / mL; or a range of values ​​consisting of any two of the above points.

[0030] According to some embodiments of the present invention, if the magnetic microrobot contains a drug, the mixture obtained in step S2 also includes the drug. Depending on the solubility of the drug, it can be added in either step S1 or step S2. Specifically, if the drug is water-soluble, it is added in step S1; otherwise, it is added in step S2.

[0031] According to some embodiments of the present invention, in step S3, the temperature of the mixture used is 50~65°C. For example, it can be 50°C, 55°C, 60°C, 65°C; or a range of values ​​consisting of any two of the above points.

[0032] According to some embodiments of the present invention, in step S3, the device used for dripping includes a microfluidic pump.

[0033] According to some embodiments of the present invention, the syringe used in the microfluidic pump has a size of 21G, 25G or 30G.

[0034] According to some embodiments of the present invention, in step S3, the dripping rate is 1~3 mL / min. Specifically, it can be 1 mL / min, 1.1 mL / min, 1.2 mL / min, 1.3 mL / min, 1.4 mL / min, 1.5 mL / min, 1.6 mL / min, 1.7 mL / min, 1.8 mL / min, 1.9 mL / min, 2 mL / min, 2.1 mL / min, 2.2 mL / min, 2.3 mL / min, 2.4 mL / min, 2.5 mL / min, 2.6 mL / min, 2.7 mL / min, 2.8 mL / min, 2.9 mL / min, or 3 mL / min; or a range of values ​​consisting of any two of the above points.

[0035] According to some embodiments of the present invention, in step S3, the temperature after cooling is ≤10℃. For example, it can be stored in a refrigerator at 4℃ for 12 hours.

[0036] According to an embodiment of a third aspect of the present invention, a targeted drug is provided, wherein the raw materials for preparing the targeted drug include the magnetic microrobot described in the first aspect of the present invention.

[0037] Since the targeted drug adopts all the technical solutions of the magnetic microrobots in the above embodiments, it has at least all the beneficial effects brought about by the technical solutions in the above embodiments.

[0038] Other features and advantages of the invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the invention. Attached Figure Description

[0039] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which: Figure 1 This is a schematic diagram of the microfluidic pump forming droplets in step S3 of an embodiment of the present invention.

[0040] Figure 2 This is the appearance morphology of the magnetic microrobot obtained in Embodiment 1 of the present invention.

[0041] Figure 3 This refers to the particle size of the series of magnetic microrobots obtained in Embodiment 3 of the present invention.

[0042] Figure 4 This describes the relationship between the motion rate of the magnetic microrobots obtained in Embodiments 1, 4, and 5 of this invention and the rotation frequency of the rotating magnetic field.

[0043] Figure 5 This describes the microstructure and elemental distribution of the magnetic microrobot obtained in Embodiment 1 of the present invention.

[0044] Figure 6 This describes the controllable motion and trajectory of the magnetic microrobot obtained in Embodiment 1 of the present invention under magnetic field control.

[0045] Figure 7 The storage modulus (G`) and loss modulus (G``) of the magnetic microrobots obtained in Comparative Example 2 (gelatin) and Example 1 (gelatin + PVA + SA) of this invention change with temperature.

[0046] Figure 8 This is the degradation of the magnetic microrobot obtained in Example 1 of the present invention under infrared light irradiation.

[0047] Figure 9 It refers to the appearance and cumulative release ratio of contents of the magnetic microrobot obtained in Embodiment 1 of the present invention, whether it has been irradiated with infrared light.

[0048] Figure 10 This is the motion trajectory of the magnetic microrobot obtained in Embodiment 1 of the present invention before and after infrared light irradiation.

[0049] Figure 11 This is the result of whether the magnetic microrobot obtained in Embodiment 1 of the present invention has been exposed to infrared light and whether the contents of the robot are released.

[0050] Figure 12 The temperature change trend and appearance of the magnetic microrobots obtained in Embodiments 1, 4-5 of this invention in a high-frequency alternating magnetic field. Detailed Implementation

[0051] The following will describe the concept and technical effects of the present invention clearly and completely with reference to embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention.

[0052] Example 1 This example provides a miniature magnetic robot and its fabrication method. The specific steps of the fabrication method are as follows: S1. Heat the PVA (polyvinyl alcohol) by mass percentage to 90°C until it is completely dissolved in deionized water and then cool it. Mix it with gelatin, sodium alginate and water with a Bloom value of 340 and heat it to 55~65°C (a comparable technical effect can be obtained within this range, and 60°C is selected in this example) until it is completely dissolved to obtain a mixed aqueous solution. The mass concentrations of PVA, sodium alginate, and gelatin in the mixed aqueous solution are shown in Table 1.

[0053] S2. Add iron oxide powder with a particle size of 200~800nm ​​to the mixed aqueous solution obtained in step S1 so that the mass-volume ratio of iron oxide to the mixed aqueous solution is 0.4g / mL; S3. Reference Figure 1 The method involves injecting the mixture obtained in step S2 into a syringe pump at a constant temperature of 55°C and then pumping it into the mineral oil at a constant speed of 2 mL / min using a 30G microfluidic pump. During the process, the three-dimensional displacement platform at the bottom of the mineral oil container is moved to prevent the droplets from merging.

[0054] After the mineral oil is dripped in, the container holding it is placed in a 4°C refrigerator for 12 hours to allow the magnetic microrobot to solidify.

[0055] Example 2 and Comparative Examples 1-8 disclose a magnetic microrobot and its fabrication method, respectively. The specific differences from Example 1 are as follows: The composition of the gel matrix is ​​different, specifically the solute in the mixed aqueous solution obtained in step S1 is different; the solute in the mixed aqueous solution is shown in Table 1; the other steps, conditions and examples are exactly the same.

[0056] Table 1. Composition of the mixed aqueous solution obtained in step S1 of Examples 1-2 and Comparative Examples 1-8.

[0057] Group Gelatin content (wt%) Sodium alginate content (wt%) Polyvinyl alcohol content (wt%) Comparative Example 1 5 0 0 Comparative Example 2 10 0 0 Comparative Example 3 10 0.5 0 Comparative Example 4 10 1 0 Comparative Example 5 10 1.5 0 Comparative Example 6 10 0 5 Comparative Example 7 10 0 10 Comparative Example 8 10 0 15 Example 2 10 0.5 10 Example 1 10 1 10 Example 3 This example provides a series of miniature magnetic robots and their fabrication methods, wherein the specific differences from Example 1 are as follows: In step S3, the model of the injection pump and the injection speed of the microfluidic pump used are different, and the specific differences are shown in Table 2.

[0058] Table 2 lists the syringe pump models and injection speeds in Examples 1 and 3. serial number Injection pump model Injection rate mL / min serial number Injection pump model Injection rate mL / min serial number Injection pump model Injection rate mL / min 1 21G 1.0 12 25G 1.0 23 30G 1.0 2 21G 1.2 13 25G 1.2 24 30G 1.2 3 21G 1.4 14 25G 1.4 25 30G 1.4 4 21G 1.6 15 25G 1.6 26 30G 1.6 5 21G 1.8 16 25G 1.8 27 30G 1.8 6 21G 2.0 17 25G 2.0 28 (Example 1) 30G 2.0 7 21G 2.2 18 25G 2.2 29 30G 2.2 8 21G 2.4 19 25G 2.4 30 30G 2.4 9 21G 2.6 20 25G 2.6 31 30G 2.6 10 21G 2.8 21 25G 2.8 32 30G 2.8 11 21G 3.0 22 25G 3.0 33 30G 3.0 Example 4 This example provides a series of miniature magnetic robots and their fabrication methods, which differ from Example 1 in that: In step S2, the mass-to-volume ratio of ferric oxide to the mixed aqueous solution is 0.3 g / mL. All other conditions are the same as in Example 1.

[0059] Example 5 This example provides a series of miniature magnetic robots and their fabrication methods. The specific differences from Example 1 are as follows: In step S2, the mass-to-volume ratio of ferric oxide to the mixed aqueous solution is 0.5 g / mL. All other conditions are the same as in Example 1.

[0060] Test case The first aspect of this example tested the morphology and elemental composition of the magnetic microrobots obtained in the embodiments and comparative examples. The testing methods were scanning electron microscopy (with EDS plugin) and optical microscopy. The test results of the magnetic microrobot obtained in Example 1 are as follows: Figure 2 and Figure 5 As shown, Figure 2 The scale bar in the illustration is 250 μm. Figure 5 The scale bar size is 100 μm. The results show that the magnetic microrobot prepared by this invention has a spherical or near-spherical morphology; Na, C, and Fe are uniformly distributed, and the positions of Fe and other elements are complementary; thus, it is clear that in the magnetic microrobot provided by this invention, nano-iron oxide particles are dispersed in the gel matrix, and sodium alginate and other components in the gel matrix are uniformly distributed. The test results of other embodiments differ from those of Example 1 only in particle size; the elemental distribution is comparable.

[0061] The second aspect of this example uses an optical microscope to measure the particle size of the magnetic microrobots obtained under different conditions in Example 3. Specific test results are as follows: Figure 3 As shown in Table 3, the results show that as the diameter of the injection pump increases and the injection rate decreases, the particle size of the obtained magnetic microrobots gradually increases, with the overall particle size distribution ranging from 0.5 to 4 mm.

[0062] Table 3. Effects of injection pump diameter and injection rate on the particle size (mm) of the obtained magnetic microrobots. Flow rate (mL / min) 21G 25G 30G 1 3.856 3.215 2.153 1.2 3.624 3.045 2.075 1.4 3.482 2.975 1.523 1.6 3.394 2.751 1.365 1.8 3.286 2.635 1.242 2 3.182 2.453 0.865 2.2 3.167 2.056 0.632 2.4 3.094 1.892 0.548 2.6 3.051 1.658 0.513 2.8 2.764 1.579 0.539 3 2.519 1.532 0.496 The third aspect of this example tested the phase transition temperature of the gel matrix in Examples 1-2 and Comparative Examples 1-8, as well as the relationship between temperature and storage modulus and loss modulus. Specifically, the phase transition temperature was tested at room temperature (20°C) with the near-infrared light intensity fixed at 2 W / cm². 2 The sample size was fixed at 1g, and the distance between the near-infrared light emitter and the sample was fixed at 10cm. The storage modulus and loss modulus were tested using dynamic thermomechanical analysis; the test results are shown in Table 4 and... Figure 7 As shown.

[0063] Table 4. Phase transition temperatures of the gel matrices in Examples 1-2 and Comparative Examples 1-8, and the light exposure time required to reach the phase transition temperature. Group Phase transition temperature (°C) Corresponding near-infrared illumination time (s) Comparative Example 1 29.8 19.7 Comparative Example 2 31.9 28.9 Comparative Example 3 32.7 38.9 Comparative Example 4 33.4 41.2 Comparative Example 5 33.1 40.7 Comparative Example 6 35.9 57.3 Comparative Example 7 36.6 64.8 Comparative Example 8 36.3 63.1 Example 2 38.9 70.7 Example 1 39.6 73.6 The phase transition temperatures in Table 4 are the temperatures at which the gel matrix is ​​observed to dissolve (transform) into a liquid state.

[0064] Table 4 shows that the magnetic microrobot provided by this invention exhibits a photothermal effect. Increasing the gelatin content can raise its phase transition temperature, but the gelatin solution becomes too viscous above 10%, increasing the difficulty of preparation. Adding sodium alginate or polyvinyl alcohol alone can also increase the overall gel phase transition temperature, but it is difficult to reach a critical value slightly above body temperature. The mixed gel formed by incorporating both into gelatin can reach a phase transition temperature of around 39 degrees Celsius, making the magnetic microrobot relatively stable and less prone to degradation within a body temperature environment. It only undergoes controlled degradation and release under near-infrared light irradiation at the target location.

[0065] Figure 7 The results showed that for the gelatin sample, its storage modulus was comparable to its loss modulus at about 35°C, indicating that it transitioned from a solid to a liquid. However, for the sample with added PVA and SA, this transition point was raised to about 38°C.

[0066] The fourth aspect of this example tested the heating and release behavior of the magnetic microrobots obtained in Examples 1, 4-5 under infrared irradiation. During the test, the ambient temperature was 20°C, the distance between the near-infrared light emitter and the magnetic microrobot was fixed at 10 cm, the magnetic microrobot was immersed in PBS solution to a depth of 4 mm, and the infrared light intensity was fixed at 2 W / cm². 2 The magnetic microrobot obtained in Example 1 operates at 2W / cm². 2 The process of decomposing and releasing nano-magnetic particles under infrared light intensity irradiation is as follows: Figure 8 As shown; the magnetic microrobot obtained in Example 1 was subjected to a 2W / cm 2 The release ratio of the contents (referring to the nanomagnetic particles) after irradiation with infrared light for 30 min followed by standing for 12 h, and after standing for 12 h without infrared light irradiation and stably dispersed in PBS solution, was as follows: Figure 9 As shown, the specific test process and test data are as follows: Figure 11 As shown.

[0067] The results showed that the heating rate of the magnetic microrobots gradually increased with the increase of the content of nanomagnetic particles in the magnetic microrobots and the increase of the intensity of the infrared light used. Once the temperature reached the phase transition temperature of the gel matrix, the magnetic microrobots disintegrated, releasing the clusters of nanomagnetic particles within them. Figure 9 and Figure 11The results show that after infrared irradiation, the magnetic microrobot of Example 1 releases approximately 86.48% of its components within 90 minutes, and reaches a release equilibrium at 90 minutes. However, without infrared irradiation, the release rate is only 5.51%. This indicates that the magnetic microrobot provided by the present invention exhibits very low loss of effective components during long-range targeting before infrared irradiation, and a high release rate after infrared irradiation, enabling precise targeted delivery.

[0068] The fifth aspect of this example tested the heating rate and release behavior of the magnetic microrobots obtained in Examples 1, 4-5 under a high-frequency alternating magnetic field. During the test, the power of the high-frequency alternating magnetic field was 12 kW, and the frequency was 500 kHz. The results showed that at the same time point, the temperature of the obtained magnetic microrobots increased with the increase of the content of nanomagnetic particles in the magnetic microrobots; the longer the same type of magnetic microrobot remained in the high-frequency alternating magnetic field, the higher the temperature. Once the temperature reached the phase transition temperature of the gel, the obtained magnetic microrobots disintegrated and released the clusters of nanomagnetic particles. The temperature change trends of the magnetic microrobots obtained in Examples 1, 4-5 in the high-frequency alternating magnetic field, and the morphologies of the magnetic microrobot obtained in Example 5 at 0s and 120s are shown below. Figure 12 As shown.

[0069] In the sixth aspect of this example, the movement of the magnetic microrobots obtained in the embodiments under a 6 mT rotating magnetic field was tested. The test results regarding the relationship between the movement speed of the magnetic microrobots obtained in Examples 1 and 4-5 and the rotation frequency of the rotating magnetic field are as follows: Figure 4 As shown; the controllable motion and trajectory of the magnetic microrobot obtained in Example 1 under magnetic field control are as follows. Figure 6 As shown (magnetic field frequency 2Hz); the magnetic microrobot obtained in Example 1, under magnetic field control, has a strength of 2W / cm². 2 The motion trajectory before and after 80 seconds of infrared light intensity irradiation is as follows Figure 10 As shown (magnetic field frequency 2Hz). The results show that the magnetic microrobots obtained in Examples 1, 4, and 5 can all move in a directional manner under the control of an external magnetic field, and the moving speed first increases and then decreases with the increase of the magnetic field rotation frequency. Before infrared irradiation, the magnetic microrobots have a large particle size, excellent long-range targeting effect, and fast movement speed. When approaching the target position or encountering a narrow path, the magnetic microrobots can be heated by external infrared light to disintegrate and release the internal nanomagnetic particles. The nanomagnetic particles have a small particle size and can move in clusters under an external magnetic field, which is beneficial for passing through narrow paths (if there is a drug, the cluster movement can also achieve drug encapsulation movement) and achieve short-range targeting.

[0070] In summary, the phase transition temperature of the gel matrix of the magnetic microrobot provided by this invention is slightly higher than that of the human body. The gel matrix contains dispersed nano-magnetic particles, enabling it to move in a magnetic field and exhibiting photothermal effects. Therefore, it demonstrates excellent long-range targeting before heating using methods such as infrared light irradiation, and after disintegration, it releases nano-sized magnetic particles, resulting in excellent short-range targeting. Due to these properties, the magnetic microrobot provided by this invention is expected to find wide application in targeted drug development.

[0071] The embodiments of the present invention have been described in detail above with reference to the accompanying drawings. However, the present invention is not limited to the above embodiments, and various changes can be made within the scope of knowledge possessed by those skilled in the art without departing from the spirit of the present invention. Furthermore, the embodiments of the present invention and the features thereof can be combined with each other unless otherwise specified.

Claims

1. A magnetic microrobot, characterized in that, The magnetic microrobot comprises a gel matrix and nanomagnetic particles dispersed in the gel matrix; The phase transition temperature of the gel matrix is ​​38.5~40℃.

2. The magnetic microrobot according to claim 1, characterized in that, The gel matrix is ​​a mixture of polyvinyl alcohol, gelatin and sodium alginate.

3. The magnetic microrobot according to claim 2, characterized in that, The mass ratio of polyvinyl alcohol, gelatin and sodium alginate is 10:5~10:0.5~1.

4. The magnetic microrobot according to any one of claims 1 to 3, characterized in that, The nanomagnetic particles have a particle size of 200~800nm; and / or, the nanomagnetic particles include iron oxide powder.

5. The magnetic microrobot according to any one of claims 1 to 3, characterized in that, The magnetic microrobot has a spherical or near-spherical morphology; and / or, the particle size of the magnetic microrobot is 0.5~4 mm.

6. The magnetic microrobot according to any one of claims 1 to 3, characterized in that, The magnetic microrobot also includes a drug dispersed in the gel matrix.

7. A method for fabricating a magnetic microrobot as described in any one of claims 1 to 6, characterized in that, The preparation method includes the following steps: S1. Prepare a mixed aqueous solution, wherein the mixed aqueous solution includes components of the gel matrix; S2. Mix the nano-magnetic particles and the aqueous solution; S3. Add the mixture obtained in step S2 to the mineral oil and cool it down.

8. The preparation method according to claim 7, characterized in that, In the mixture obtained in step S2, the concentration of the nanomagnetic particles is 0.3 g / mL to 0.6 g / mL; and / or, in step S1, the mass concentration of sodium alginate in the mixed aqueous solution is 0.5 to 1%.

9. The preparation method according to claim 7, characterized in that, In step S3, the device used for the dripping includes a microfluidic pump; preferably, the size of the syringe used for the microfluidic pump is 21G, 25G or 30G.

10. A targeted drug, characterized in that, The raw materials for preparing the targeted drug include the magnetic microrobots as described in any one of claims 1 to 6.

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