A method for regulating the aggregation state and location of encapsulated molecules inside organic nanoparticles to form Janus nanoparticles

Abstract

The application belongs to the technical field of particle morphology regulation, and discloses a method for regulating the aggregation state and position of embedded molecules in organic nanoparticles to form Janus nanoparticles. The method comprises the following steps: mixing organic photothermal molecules, polylactic acid-glycolic acid copolymer and dichloromethane to obtain a dichloromethane mixed solution; mixing polyvinyl alcohol and water and then keeping the mixture at temperature to obtain a polyvinyl alcohol solution; ultrasonically mixing the dichloromethane mixed solution and the polyvinyl alcohol solution, stirring to remove dichloromethane, centrifuging and washing to obtain Janus nanoparticles. The method has good Janus-like NP ball formation effect on several different structures of organic molecules and oleic acid modified nano Fe3O4, and has good stability, and is expected to be applied to the preparation of various organic Janus nanoparticles. The above method is simple and convenient, and has high practicability.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of particle morphology regulation, and in particular to a method for forming Janus nanoparticles by regulating the aggregation state and position of embedded molecules in organic nanoparticles. BACKGROUND

[0002] Currently, organic optical reagents have shown good application prospects in the field of photodiagnosis and treatment due to their adjustable optical physical properties, high biological safety and good biocompatibility. By preparing organic optical reagents into nanoparticles, the defects of poor water solubility and poor water dispersibility of organic molecules in the body can be well overcome, and as a drug delivery carrier, the emergence of nanoparticles provides unlimited possibilities for the treatment of cancer tumors.

[0003] Studies have shown that in addition to the characteristics brought by the structure of organic molecules, the aggregation state and position of molecules in nanoparticles will also affect the optical physical properties of organic nanoparticles. For example, AIE (aggregation-induced emission) fluorophores can improve their fluorescence quantum efficiency through a more compact aggregation state, which is conducive to the improvement of imaging effect, while traditional ACQ (aggregation caused quenching) photothermal molecules will quench their fluorescence under a more compact packing, thereby improving their photothermal effect. Therefore, regulating the aggregation state of molecules in nanoparticles plays an important role in improving photodiagnosis and treatment effect. In addition, Janus nanoparticles formed by the non-uniform distribution of organic molecules in nanoparticles will also bring new properties to the nanoparticles, such as the motion ability of nanoparticles generated by the temperature gradient of asymmetric distribution of photothermal reagents. However, there are few studies on the regulation of the aggregation state of molecules in nanoparticles, and most of the research on Janus nanoparticles is concentrated in the inorganic field, which is relatively cumbersome to prepare and cannot be applied to pure organic nanoparticles. Therefore, it is urgent to develop a stable and versatile method to control the aggregation state and position of embedded components in nanoparticles to form pure organic Janus nanoparticles. SUMMARY

[0004] The purpose of the present application is to provide a method for forming Janus nanoparticles by regulating the aggregation state and position of embedded molecules in organic nanoparticles, which solves the problem that the existing method for preparing Janus nanoparticles cannot be applied to pure organic nanoparticles.

[0005] In order to achieve the above-mentioned application purpose, the present application provides the following technical solutions:

[0006] The present application provides a method for forming Janus nanoparticles by regulating the aggregation state and position of embedded molecules in organic nanoparticles, comprising the following steps:

[0007] (1) mixing the organic photothermal molecules, polylactic acid-glycolic acid copolymer and dichloromethane to obtain a dichloromethane mixed solution; mixing the polyvinyl alcohol and water and keeping warm to obtain a polyvinyl alcohol solution;

[0008] (2) mixing the dichloromethane mixed solution and the polyvinyl alcohol solution by ultrasonic mixing, stirring to remove dichloromethane, centrifuging and washing to obtain Janus nanoparticles;

[0009] The organic photothermal molecules include any one of organic molecules with a planar conjugated structure, AIE organic molecules with a TPA rotor structure, porphyrin organic molecules or oleic acid modified nano Fe3O4.

[0010] Further, in the above method, the mass-volume ratio of the organic photothermal molecules, polylactic acid-glycolic acid copolymer and dichloromethane in step (1) is 1g: 9-12g: 2L, and the mass concentration of polyvinyl alcohol in the polyvinyl alcohol solution in step (1) is 0.15-0.25%.

[0011] Further, in the above method, the temperature of keeping warm in step (1) is 0-5℃, and the time of keeping warm is 8-15min.

[0012] Further, in the above method, the organic molecules with a planar conjugated structure include DMA-BDTO, and the structural formula of DMA-BDTO is:

[0013]

[0014] The AIE organic molecules with a TPA rotor structure include TPASIC, and the structural formula of TPASIC is:

[0015]

[0016] The porphyrin organic molecules include BLSS, and the structural formula of BLSS is:

[0017]

[0018] The particle size of the oleic acid modified nano Fe3O4 is 5-10nm.

[0019] Further, in the above method, the volume ratio of the dichloromethane mixed solution and the polyvinyl alcohol solution in step (2) is 1: 11-13.

[0020] Further, in the above method, the power of ultrasonic mixing in step (2) is 62.5-87.5W, and the time of ultrasonic mixing in step (2) is 1.5-2.5min.

[0021] Further, in the above method, the stirring speed in step (2) is 180-220 rpm, and the stirring time in step (2) is 10-14 h.

[0022] Further, in the above method, the centrifugation and washing in step (2) is as follows: the nanoparticle suspension obtained after stirring to remove dichloromethane is first centrifuged at 8700-9200 rpm for 25-35 min, resuspended and washed with water, the above operation is repeated for more than 2 times, then centrifuged at 2600-3300 rpm for 3-7 min, and the obtained supernatant is the Janus nanoparticles.

[0023] According to the above technical solution, compared with the prior art, the present application has the following beneficial effects:

[0024] The present application provides a universal preparation method for preparing pure organic Janus nanoparticles, by changing the concentration of polyvinyl alcohol and the stirring rate of dichloromethane volatilization, stable pure organic Janus nanoparticles with organic molecules aggregated on one side of the inside are obtained, this method has good Janus-like NPs ball forming effect for several different structures of existing organic molecules (planar conjugated structure, TPA rotor structure, porphyrin structure), only need to fine-tune the polyvinyl alcohol concentration and ultrasonic power in the experimental process to obtain the morphology of nanoparticles with components aggregated on one side of the inside, in theory, this method has good applicability for molecules with good solubility in dichloromethane, is expected to be applied to the preparation of various organic molecule Janus nanoparticles, and has good effect for oleic acid modified nano Fe3O4 particles. The method of the present application is simple and convenient, has strong practicability, and the obtained nanoparticles have good stability. BRIEF DESCRIPTION OF DRAWINGS

[0025] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed to be used in the embodiments or prior art description will be briefly introduced as follows.

[0026] Figure 1 TEM image of oleic acid modified nano Fe3O4;

[0027] Figure 2 Schematic diagram for preparing pure organic Janus nanoparticles and preparing uniformly distributed nanoparticles;

[0028] Figure 3 TEM image of Janus-like NPs of DMA-BDTO obtained in Example 1;

[0029] Figure 4 TEM image of Homo-NPs of DMA-BDTO obtained in Comparative Example 1;

[0030] Figure 5 TEM image of DMA-BDTO with morphology between Janus-like NPs and Homo-NPs for Comparative Example 2;

[0031] Figure 6 Particle size distribution plot of Janus-like NPs of DMA-BDTO for Example 1 over 15 days;

[0032] Figure 7 Absorption emission curve plot of Janus-like NPs of DMA-BDTO for Example 1 and Homo-NPs of DMA-BDTO for Comparative Example 1;

[0033] Figure 8 Trajectory plot of Janus-like NPs of DMA-BDTO for Example 1;

[0034] Figure 9 Trajectory plot of Homo-NPs of DMA-BDTO for Comparative Example 1;

[0035] Figure 10 Mean square displacement plot of Janus-like NPs of DMA-BDTO for Example 1 and Homo-NPs of DMA-BDTO for Comparative Example 1;

[0036] Figure 11 TEM image of Janus-like NPs of TPASIC for Example 2;

[0037] Figure 12 TEM image of Janus-like NPs of BLSS for Example 3;

[0038] Figure 13 TEM image of Janus-like NPs of oleic acid modified Fe3O4 for Example 4;

[0039] Figure 14 Dynamic light scattering particle size distribution plot of Janus-like NPs of DMA-BDTO for Example 1;

[0040] Figure 15 Dynamic light scattering particle size distribution plot of Janus-like NPs of TPASIC for Example 2;

[0041] Figure 16 Dynamic light scattering particle size distribution plot of Janus-like NPs of BLSS for Example 3;

[0042] Figure 17Dynamic light scattering particle size distribution diagram of the Janus-like NPs of the oleic acid modified Fe3O4 obtained in Example 4. DETAILED DESCRIPTION

[0043] The application provides a method for regulating the aggregation state and position of embedded molecules in organic nanoparticles to form Janus nanoparticles, comprising the following steps:

[0044] (1) ultrasonically mix organic photothermal molecules, polylactic acid-glycolic acid copolymer and dichloromethane at room temperature (20-25 DEG C) in a water bath, and obtain a dichloromethane mixed solution after sufficient dispersion; stir the polylactic acid-glycolic acid copolymer and water in an oil bath at 90 DEG C for 3 hours, and obtain a polylactic acid-glycolic acid copolymer solution after heat preservation;

[0045] (2) ultrasonically mix the dichloromethane mixed solution and the polylactic acid-glycolic acid copolymer solution, remove dichloromethane by stirring, centrifuge and wash, and obtain Janus nanoparticles;

[0046] The organic photothermal molecules include any one of organic molecules with a planar conjugated structure, AIE organic molecules with a TPA rotor structure, porphyrin organic molecules or oleic acid modified nano Fe3O4.

[0047] In the application, the mass-volume ratio of the organic photothermal molecules, polylactic acid-glycolic acid copolymer and dichloromethane in step (1) is preferably 1g:9-12g:2L, further preferably 1g:10-11g:2L, and more preferably 1g:10g:2L.

[0048] In the application, the power of the ultrasonic in step (1) is preferably 1200-1600W, further preferably 1350-1480W, and more preferably 1400W.

[0049] In the application, the time of the ultrasonic in step (1) is preferably 5-10min, further preferably 7-9min, and more preferably 8min.

[0050] In the application, the mass concentration of the polylactic acid-glycolic acid copolymer in the polylactic acid-glycolic acid copolymer solution in step (1) is preferably 0.15-0.25%, further preferably 0.18-0.22%, and more preferably 0.20%.

[0051] In the application, the temperature of the heat preservation in step (1) is preferably 0-5 DEG C, further preferably 2-4 DEG C, and more preferably 4 DEG C, so as to avoid high temperature in step (2) and fast volatilization of dichloromethane.

[0052] In the application, the time of the heat preservation in step (1) is preferably 8-15min, further preferably 9-12min, and more preferably 10min.

[0053] In the present application, the organic molecule with planar conjugated structure comprises DMA-BDTO, and the structural formula of DMA-BDTO is as follows:

[0054]

[0055] The AIE organic molecule with TPA rotor structure comprises TPASIC, and the structural formula of TPASIC is as follows:

[0056]

[0057] The porphyrin organic molecule comprises BLSS, and the structural formula of BLSS is as follows:

[0058]

[0059] In the present application, the particle size of the oleic acid modified nano Fe3O4 is preferably 5-10 nm, further preferably 6-8 nm, and more preferably 7 nm.

[0060] In the present application, the volume ratio of the dichloromethane mixed solution to the polyvinyl alcohol solution in step (2) is preferably 1:11-13, further preferably 1:11.5-12.2, and more preferably 1:12.

[0061] In the present application, the power of the ultrasonic in step (2) is preferably 62.5-87.5 W, further preferably 68-78 W, and more preferably 75 W.

[0062] In the present application, the time of the ultrasonic in step (2) is preferably 1.5-2.5 min, further preferably 1.7-2.1 min, and more preferably 2 min.

[0063] In the present application, the speed of the stirring in step (2) is preferably 180-220 rpm, further preferably 192-214 rpm, and more preferably 200 rpm.

[0064] In the present application, the time of the stirring in step (2) is preferably 10-14 h, further preferably 11.6-12.7 h, and more preferably 12 h.

[0065] In the present application, the centrifugation and washing in step (2) is preferably as follows: the nanoparticle suspension obtained after removal of dichloromethane by stirring is first centrifuged at 8700-9200 rpm for 25-35 min, resuspended and washed with water, the above operation is repeated for 2 times or more, then centrifuged at 2600-3300 rpm for 3-7 min, and the supernatant obtained is the Janus nanoparticles; further preferably, the nanoparticle suspension obtained after removal of dichloromethane by stirring is first centrifuged at 8920-9080 rpm for 28-32 min, resuspended and washed with water, the above operation is repeated for 3 times or more, then centrifuged at 2860-3150 rpm for 4-6 min, and the supernatant obtained is the Janus nanoparticles; more preferably, the nanoparticle suspension obtained after removal of dichloromethane by stirring is first centrifuged at 9000 rpm for 30 min, resuspended and washed with water, the above operation is repeated for 3 times, then centrifuged at 3000 rpm for 5 min, and the supernatant obtained is the Janus nanoparticles.

[0066] In the present application, the water used in step (1) and the washing in step (2) is Milli-Q ultrapure water.

[0067] The technical solutions in the embodiments of the present application will be described below in a clear and complete manner. Obviously, the described embodiments are only some of the embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0068] Embodiment 1

[0069] The present embodiment provides a method for regulating the aggregation state and position of the embedded molecules in the organic nanoparticles to form Janus nanoparticles, comprising the following steps:

[0070] (1) 0.5 mg of DMA-BDTO and 5 mg of polylactic acid glycolic acid (PLGA) are mixed in 1 mL of dichloromethane (DCM) in a 5 mL plastic centrifuge tube, and an Elmasonic P 180H ultrasonic cleaning device is used for ultrasonic treatment at 1400 W in a room temperature water bath for 10 min to obtain a dichloromethane mixed solution;

[0071] (2) Take a 250 mL round-bottom flask, first add 12.5 g of polyvinyl alcohol, then add 150 mL of Milli-Q ultrapure water (to avoid the problem of polyvinyl alcohol sticking to the bottle opening or bottle wall when water is added), then add a magnetic sonicator, heat at 90°C oil bath and 600 rpm for 3 h to obtain a polyvinyl alcohol solution with a mass concentration of 5%; the prepared polyvinyl alcohol solution is divided into 50 mL centrifuge tubes and a certain amount is diluted according to a polyvinyl alcohol concentration of 0.2%, 12 mL of 0.2% polyvinyl alcohol solution is added to a 20 mL transparent glass bottle, and placed in a 4°C refrigerator for 10 min for standby;

[0072] (3) 1 mL of the ultrasonically treated 1 mL dichloromethane mixed solution is quickly added to the transparent glass bottle containing 12 mL of polyvinyl alcohol solution using a 1 mL syringe, the probe of the Qsonica Q125 small ultrasonic crusher is inserted into the glass bottle to the middle of the liquid surface, and immediately ultrasonic treatment is carried out at room temperature at a power of 75 W for 2 min, while rotating the transparent glass bottle around the probe with the hand to complete the ultrasonic treatment; after the ultrasonic treatment is completed, a magnetic sonicator is immediately placed in the transparent glass bottle, and stirring is carried out at a speed of 200 rpm in a fume hood at room temperature for 12 h, and after the DCM is volatilized, the solution in the transparent glass bottle is transferred to a 15 mL centrifuge tube, centrifuged at 9000 rpm for 30 min to precipitate the nanoparticles, remove the supernatant, and add Milli-Q ultrapure water to resuspend, which is a one-time washing process, mainly to remove polyvinyl alcohol and molecules that do not form nanoparticles; after three washes, centrifugation is carried out at 3000 rpm to remove larger nanoparticles, and the supernatant is retained, i.e. the Janus-like NPs of DMA-BDTO are obtained.

[0073] Take 1 mL of the above prepared Janus-like NPs of DMA-BDTO to test the particle size by dynamic light scattering instrument, and the results show that the particle size is concentrated at about 110.7 nm.

[0074] Comparative Example 1

[0075] The difference between Comparative Example 1 and Example 1 is that the concentration of the polyvinyl alcohol solution prepared in step (2) and placed in a 4°C refrigerator for 10 min for standby is 2.5%, the speed of magnetic stirring in step (3) is 800 rpm, and the other preparation procedures and conditions are the same as those in Example 1, to obtain the DMA-BDTO molecules uniformly distributed in the nanoparticles Homo-NPs.

[0076] Comparative Example 2

[0077] Comparative Example 2 differs from Example 1 in that the speed of magnetic stirring in step (3) is 800 rpm, and other preparation procedures and conditions are the same as those in Example 1, to obtain nanoparticles with internal morphology of DMA-BDTO molecules between Janus-like NPs and Homo-NPs.

[0078] Figure 2 Schematic diagram for preparing pure organic Janus nanoparticles and Homo-NPs nanoparticles with internal uniform distribution (taking DMA-BDTO molecules as an example). In this process, two morphologies as shown in Figure 2 are prepared by controlling the concentration of PVA and the evaporation speed of DCM during the formation of nanoparticles, which is due to the phase separation process induced by DCM evaporation during the formation of nanoparticles: DMA-BDTO as an organic photothermal molecule has strong hydrophobicity and higher solubility in DCM than PLGA. During the probe sonication, the DCM solution containing DMA-BDTO and PLGA is dispersed into individual oil-in-water emulsion droplets, and the amphiphilic PVA surfactant stabilizes the DCM emulsion droplets to better form nanoparticles. When DCM evaporates from the emulsion droplets, DMA-BDTO molecules aggregate on one side of the nanoparticles to minimize the interfacial tension. At a lower PVA concentration (0.2%) and a slower DCM evaporation rate (200 rpm), DMA-BDTO will gradually concentrate and aggregate to the side of the emulsion where DCM evaporates, and finally precipitate on one side of the nanoparticles to form Janus-like NPs with one side aggregation. In the case of high PVA concentration (2.5%), the movement of DMA-BDTO and PLGA molecules is constrained by PVA, and faster DCM evaporation (900 rpm) can quickly fix these DMA-BDTO molecules, and before they aggregate on one side, DCM is evaporated and forms Homo-NPs with internal uniform distribution. Therefore, by reducing the PVA concentration and the DCM evaporation speed (magnetic stirring rate), pure organic Janus nanoparticles can be obtained.

[0079] Figure 3 、 Figure 4 、 Figure 5 TEM images of DMA-BDTO nanoparticles obtained in Example 1, Comparative Example 1 and Comparative Example 2, respectively. By comparing the TEM images of the three kinds of nanoparticles, it can be found that lower PVA concentration and lower magnetic stirring speed are very important for forming Janus-like NPs with molecules aggregated on one side inside.

[0080] Figure 6The size distribution of the Janus-like NPs of DMA-BDTO obtained in Example 1 stored at 4℃ for 15 days is shown in the figure, and the size is basically distributed at about 110 nm, and the size does not change obviously, indicating that the Janus-like NPs prepared in Example 1 have good stability.

[0081] Figure 7 The absorption and emission curves of the Janus-like NPs of DMA-BDTO obtained in Example 1 and the Homo-NPs of DMA-BDTO obtained in Comparative Example 1. The DMA-BDTO molecule is an organic photothermal molecule, and has the characteristic of aggregation-induced fluorescence quenching, as shown in Figure 7 The Homo-NPs show higher emission than the Janus-like NPs at higher absorption, which indicates that the DMA-BDTO molecules inside the Janus-like NPs prepared in Example 1 have a more compact packing, resulting in stronger fluorescence quenching, indicating that the method can effectively regulate the aggregation state of the internal molecules, thereby affecting the photophysical properties.

[0082] Figure 8 The motion trajectory of the Janus-like NPs of DMA-BDTO obtained in Example 1, Figure 9 The motion trajectory of the Homo-NPs of DMA-BDTO obtained in Comparative Example 1, Figure 10 The mean square displacement graph of the Janus-like NPs of DMA-BDTO obtained in Example 1 and the Homo-NPs of DMA-BDTO obtained in Comparative Example 1. Because the DMA-BDTO molecule has a photothermal effect, it is aggregated on one side inside the Janus-like NPs, and the side generates a temperature gradient under light, thereby improving the active motion ability of the Janus-like NPs, and the motion trajectory graph and the mean square displacement graph also prove this point, which indicates that the regulation of the aggregation position of the organic component by the method can bring new performance to the nanoparticles, and has a certain value for improving the photodiagnosis and treatment effect of organic nanoparticles.

[0083] Example 2

[0084] The difference between Example 2 and Example 1 is that in step (1), 0.5 mg of TPASIC and 5 mg of PLGA are mixed in 1 mL of DCM in a 5 mL plastic centrifuge tube, and the other preparation procedures and conditions are the same as those of Example 1, to obtain Janus-like NPs of TPASIC.

[0085] Example 3

[0086] Example 3 is different from Example 1 in that 0.5 mg of BLSS and 5 mg of PLGA are mixed in 1 mL of DCM in a 5 mL plastic centrifuge tube in step (1), the polyvinyl alcohol solution used in step (2) is cooled in a 4°C refrigerator for 10 min, the concentration of the polyvinyl alcohol solution used is 0.15%, the power of the ultrasonic probe used in step (3) is 62.5 W at room temperature, and the other preparation procedures and conditions are the same as in Example 1 to obtain Janus-like NPs of BLSS.

[0087] Example 4

[0088] Example 4 is different from Example 1 in that 0.5 mg of oleic acid modified Fe3O4 and 5 mg of PLGA are mixed in 1 mL of DCM in a 5 mL plastic centrifuge tube in step (1), the polyvinyl alcohol solution used in step (2) is cooled in a 4°C refrigerator for 10 min, the concentration of the polyvinyl alcohol solution used is 0.25%, the power of the ultrasonic probe used in step (3) is 87.5 W at room temperature, and the other preparation procedures and conditions are the same as in Example 1 to obtain Janus-like NPs of oleic acid modified Fe3O4.

[0089] Figure 3 、 Figure 11 、 Figure 12 、 Figure 13 are TEM images of the Janus-like NPs obtained in Example 1, Example 2, Example 3 and Example 4, respectively. As shown in the images, by fine-tuning the concentration of polyvinyl alcohol and the power of the ultrasonic probe, Janus-like NPs with other molecules aggregated on one side of the nanoparticles can be stably obtained. The same effect is also achieved for oleic acid modified Fe3O4.

[0090] Figure 14 、 Figure 15 、 Figure 16 、 Figure 17 are dynamic light scattering particle size distribution diagrams of the Janus-like NPs obtained in Example 1, Example 2, Example 3 and Example 4, respectively. The hydrodynamic diameter of the prepared Janus-like NPs is about 100-200 nm.

[0091] The above only describes preferred embodiments of the present application, and it should be noted that for those skilled in the art, without departing from the principles of the present application, a number of improvements and refinements can be made, and these improvements and refinements should also be considered as falling within the scope of the present application.

Claims

1. A method of regulating the aggregation state and position of an embedded molecule inside an organic nanoparticle to form a Janus nanoparticle, characterized by, The method comprises the following steps: (1) mixing organic photothermal molecules, polylactic acid-glycolic acid copolymer and dichloromethane to obtain a dichloromethane mixed solution; mixing polyvinyl alcohol and water and then keeping the mixture at a temperature to obtain a polyvinyl alcohol solution; (2) mixing the dichloromethane mixed solution and the polyvinyl alcohol solution by ultrasonic mixing, stirring to remove dichloromethane, centrifuging and washing to obtain Janus nanoparticles; The organic photothermal molecules comprise any one of an organic molecule with a planar conjugated structure, an AIE organic molecule with a TPA rotor structure or a porphyrin-based organic molecule; The organic photothermal molecules are optionally replaced by oleic acid modified nano Fe3O4; The organic molecule with a planar conjugated structure comprises DMA-BDTO, and the structural formula of DMA-BDTO is as follows: ； The AIE organic molecule with a TPA rotor structure comprises TPASIC, and the structural formula of TPASIC is as follows: ； The porphyrin-based organic molecule comprises BLSS, and the structural formula of BLSS is as follows: ； The particle size of the oleic acid modified nano Fe3O4 is 5-10 nm; In step (1), the mass-volume ratio of the organic photothermal molecules, polylactic acid-glycolic acid copolymer and dichloromethane is 1 g:9-12 g:2 L, and in step (1), the mass concentration of polyvinyl alcohol in the polyvinyl alcohol solution is 0.15-0.25 %; In step (2), the volume ratio of the dichloromethane mixed solution and the polyvinyl alcohol solution is 1:11-13; In step (2), the stirring speed is 180-220 rpm, and the stirring time is 10-14 h.

2. The method of claim 1, wherein, In step (1), the temperature for keeping the mixture at a temperature is 0-5 ℃, and the keeping time is 8-15 min.

3. The method of claim 1, wherein, In step (2), the ultrasonic power is 62.5-87.5 W, and the ultrasonic time is 1.5-2.5 min.

4. The method of claim 1, wherein, In step (2), the centrifuging and washing mode is as follows: after stirring to remove dichloromethane, the obtained nanoparticle suspension is first centrifuged at 8700-9200 rpm for 25-35 min, resuspended and washed with water, the above operation is repeated for more than 2 times, then centrifuged at 2600-3300 rpm for 3-7 min, and the obtained supernatant is the Janus nanoparticles.

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