CN114471750A - Method for reliably synthesizing nano/submicron droplets by inducing liquid-liquid phase separation and application thereof - Google Patents
Method for reliably synthesizing nano/submicron droplets by inducing liquid-liquid phase separation and application thereof Download PDFInfo
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- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 2
- -1 silicon dioxide-tetramethoxysilane Chemical compound 0.000 claims 2
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- NTPSYCFWEYOKTG-UHFFFAOYSA-N dioxosilane;tetraethyl silicate Chemical compound O=[Si]=O.CCO[Si](OCC)(OCC)OCC NTPSYCFWEYOKTG-UHFFFAOYSA-N 0.000 claims 1
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Images
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
Abstract
The invention relates to a method for reliably synthesizing nano/submicron droplets by controllably inducing liquid-liquid phase separation and application thereof, belonging to the field of nano materials. In an originally mutually soluble water-organic solvent homogeneous system, such as a water-ethanol system, a compound with a kosmotrope property is directly introduced or generated by reaction, so that the phase separation of the homogeneous system can be initiated, and the nano-scale liquid drops gradually nucleate and grow from the homogeneous system. The liquid drops generated by the method have the characteristics of small volume and good uniformity. By capturing these nano droplets, hollow nanostructures can be obtained. If certain functional compounds are introduced into the system, for example catalysts, drugs, etc. Then in the phase separation and liquid drop generation processes, the compounds can be synchronously loaded into the hollow nano structure, and a nano reactor and a drug carrier can be obtained. The method has the advantages of simple process, short production period and strong universality, and has good application prospect.
Description
Technical Field
The invention relates to a method for reliably synthesizing nano/submicron droplets by controllably inducing phase separation. And a method for synthesizing the hollow nanostructure, the egg nano-reactor and the drug carrier based on the hollow nanostructure. Belongs to the field of nanometer synthesis and manufacture.
Background
Droplets are an important tool in micro and nano synthesis. However, it is difficult to reliably generate nano/submicron-sized droplets by the conventional method. Or not to generate droplets small enough to stop at micron size, such as microfluidics (CN 102008983B); or the generated droplets are not uniform in size and have wide volume distribution, so that only a small part of the droplets can reach the nanometer/submicron level, such as a microemulsion system (CN 1077717A). It is therefore of great significance to achieve reliable synthesis of such droplets.
In conventional methods, two immiscible liquids are used to form a two-phase system, and one of the liquid phases is broken into small droplets. In microfluidics, this is achieved by means of valves; in the emulsion system, the emulsion is realized by mechanical force input such as stirring, ultrasound and the like. The method of the present invention is reverse to the conventional method, and a system originally having only a single liquid phase is spontaneously converted into a two-phase system, so that micro droplets are formed from bottom to top.
The synthesis of hollow nanostructures themselves, which act as shells, is complicated for nanoreactors and drug carriers. It is often necessary to first prepare sacrificial template nanoparticles. The template is used as a core, and an extremely thin nano shell is covered on the outer layer of the template. And then removing the template by a chemical etching method, and only keeping the shell to obtain the hollow nano structure serving as the carrier. This usually takes a ten hour period and may be achieved by high temperature and pressure reactions such as hydrothermal methods. On this basis, a separate step is also required to load a catalyst or a drug into the hollow nanostructures described above. Loading is typically accomplished by immersing the hollow nanostructured support in a catalyst or drug solution, allowing it to diffuse into the cavity of the support over a period of ten or tens of hours. (CN105907743B, CN108478806A)
The traditional preparation method has the following problems:
1. the process is too complicated. Even if only synthesizing the carrier, three parts of template, shell and etching are needed, and then loading is needed. In each step, the product needs to be purified and washed in refining, and the actual process is very complex and high in cost.
2. Sacrificial template nanoparticles lead to further cost increases. The template is used as a nano particle and belongs to a high-cost raw material; but the etching is completely carried out at the later stage, which is equivalent to one-time disposal, thereby greatly increasing the cost of the whole process.
3. The reaction method which is more severe at high temperature and high pressure, such as hydrothermal reaction, is needed, the energy consumption is high, and the safety is poor.
4. The loading process is less efficient. The loading process is dependent on the diffusion phenomenon, the soaking solution and the concentration gradient inside the soaking solution, and the loading process often requires tens of hours. In particular, some carrier shells made of degradable materials such as organic silicon and the like may be partially degraded in advance during long-term soaking, which affects the durability and the degradation process in practical application.
Thus, there is a lack of a method for producing yolk-shell nanostructures, nanoreactors and drug carriers that can be compact, fast, safe, low energy consuming, and independent of diffusion loading.
Disclosure of Invention
The invention solves the technical problem that nano/submicron droplets are difficult to be reliably synthesized. Therefore, a new idea and method are provided. Meanwhile, on the basis, the defects of multiple steps, long period, high energy consumption, poor safety and dependence on diffusion load in the synthesis of the nano reactor and the drug carrier are overcome.
In order to solve the technical problems, the technical scheme provided by the invention is as follows: a method for reliably synthesizing nano/sub-micron droplets by inducing liquid-liquid phase separation, comprising the steps of:
s1: the original system is a homogeneous mixed solvent system of mutually soluble water and an organic solvent, in particular to a mixture which only has one liquid phase and does not have split phase and is obtained by mixing two solvents which can be mutually soluble in any proportion;
s2: introducing a kosmotrope compound to enable the miscible liquid mixture which is originally one phase to be subjected to phase separation;
the kosmotrope refers to a substance which can enhance hydrogen bond network and/or intermolecular force in water, and refers to water-soluble salts or saccharides;
the kosmotrope can be directly added into a reaction system through a solution of water and/or an organic solvent; or may be produced by reaction.
S3: the phase separation process generates nano-sized minute droplets.
Preferably, the miscible mixed solvent with any ratio in step S1 includes water-ethanol, water-n-propanol, water-isopropanol, water-tert-butanol, water-acetonitrile, water-dimethylformamide, water-tetrahydrofuran, water-acetone or water-dimethylsulfoxide.
Preferably, the kosmotrope compound in step S2 includes sodium citrate, sodium oxalate, ammonium citrate, ammonium oxalate, sodium phosphate, ammonium phosphate, sodium sulfate, ammonium sulfate, copper sulfate, sodium trimesate, glucose, sucrose or sodium polyacrylate.
Preferably, the kosmotrope is formed by reaction in step S2, and the salt may be formed by neutralization by adding an acid and a base, respectively.
Preferably, the step S1 is performed by adding a thickener to suppress the merging process of the fine droplets and make the fine droplets more uniform.
In order to solve the above technical problem, the present invention proposes another technical solution: a method for reliably synthesizing nano/submicron droplets by inducing liquid-liquid phase separation for synthesizing hollow nanostructures by in situ micro-coating of said nanoscale micro-liquid, based on the use of the method of claim 1, to generate hollow nanostructures; the in situ micro-coating specifically refers to:
a. introducing raw materials which can react on the surface of the liquid drop to generate a solid shell material;
b. the solid generated by the raw materials and the solid shell generated by the material shell coat the liquid drops in situ to form the hollow nano structure.
Preferably, the shell material in step a and the raw material corresponding to the shell material comprise silica-tetramethoxysilane, silica-tetraethoxysilane, silica-tetrabutoxysilane, polydopamine-dopamine hydrochloride, polydopamine-dopamine oleate, calcium phosphate-calcium chloride, calcium phosphate-sodium phosphate, calcium phosphate-ammonium phosphate, organic metal framework HKUST-1-trimesic acid or organic metal framework HKUST-1-copper oleate.
Preferably, the method of inducing liquid-liquid phase separation to reliably synthesize nano/submicron droplets is used for the synthesis of nanoreactors or drug carriers: comprises that
S1: adding the compound to be supported to the liquid-liquid mixture; the compound to be supported is a compound having catalytic properties in the case of a nanoreactor; and in the case of a drug carrier, a drug;
the addition of the compound to be loaded is divided into two cases:
a. dissolving the mixture in a homogeneous mixed solvent system before the reaction;
b. when the kosmotrope compound is introduced, the kosmotrope compound is added together with the kosmotrope compound dissolved in the kosmotrope compound;
s2: generating micro liquid drops containing the compound to be loaded inside;
s3: and micro-coating the liquid drops to obtain a hollow nano structure containing a compound to be loaded, a nano reactor or a drug carrier.
Preferably, it is characterized in that: the method for reliably synthesizing nano/submicron droplets by inducing liquid-liquid phase separation is used for synthesizing a nano reactor and a drug carrier, and the process of loading a compound to be loaded and the process of generating a hollow nano structure are synchronously completed in one reaction.
A method for synthesizing nano/submicron droplets by controllably inducing liquid-liquid phase separation. Based on the method, a method for synthesizing the yolk-shell nano structure, the nano reactor and the drug carrier synchronously, which is simple, rapid, safe and low in energy consumption, is developed. The method comprises the following steps:
s1: in the miscible homogeneous mixed solution, a compound having a kosmotrope property is introduced to induce phase separation.
The miscible homogeneous mixed solution refers to a mixture of two solvents miscible with each other in any proportion, which has only one liquid phase and no phase separation. Including but not limited to water-ethanol, water-n-propanol, water-isopropanol, water-n-butanol, water-acetonitrile, water-dimethylformamide, water-tetrahydrofuran, water-acetone, water-dimethylsulfoxide.
The term "kosmotrope" refers to a substance having a function of enhancing hydrogen bonding networks and/or intermolecular forces in water, and refers to salts, saccharides, polyhydroxy polymers, and the like. Including but not limited to sodium citrate, ammonium phosphate, glucose, sodium polyacrylate, and the like.
The introduction may be carried out by directly adding a solution of water and/or an organic solvent to the reaction system; or by adding chemical raw materials which can generate the kosmotrope, for example, by adding citric acid and sodium hydroxide to neutralize and generate sodium citrate with the property of the kosmotrope.
S2: nano-scale droplets are generated.
S3: the raw materials of the reaction are introduced which are capable of generating a solid shell on the surface of the liquid droplet. The solid shell generated by the material coats the liquid drop in situ, and the hollow nano structure can be obtained.
S4: if the compound to be loaded is added into the system, a nano reactor or a drug carrier can be obtained.
The compound to be supported is a compound having catalytic properties in the case of a nanoreactor; and in the case of a drug carrier, a drug.
The addition may be carried out by dissolving the compound to be supported in a homogeneous mixed solvent system before the start of the reaction, or may be carried out together with the introduction of the kosmotrope compound, together with the dissolution thereof.
Advantageous effects
In conventional methods, two immiscible liquids are used to form a two-phase system, and one of the liquid phases is broken into small droplets. In microfluidics, this is achieved by means of valves; in the emulsion system, the emulsion is realized by mechanical force input such as stirring, ultrasound and the like. The method of the present invention is reverse to the conventional method, and a system originally having only a single liquid phase is spontaneously converted into a two-phase system, so that micro droplets are formed from bottom to top.
The method can reliably synthesize nano/submicron droplets by controllably inducing liquid-liquid phase separation, and thus efficiently synthesize the hollow nanostructure nano-reactor and the drug carrier.
The method has also creatively proposed a technique of inducing phase separation by saccharides having excellent biocompatibility in addition to salts.
The synthesis of the nano structure by the method can realize the synthesis of the carrier and the loading of the catalytic substance/medicine in one step without separate operations. Compared with the traditional method, the method is simpler, quicker and quicker.
The method can be realized at room temperature under normal pressure or at a lower temperature of below 100 ℃, and is safer and energy-saving.
The loading process of the method does not rely on the diffusion process. The loading capacity is large and uniform.
The method can be applied to a variety of different materials, such as silica, polydopamine, calcium phosphate, organometallic frameworks, and the like.
Drawings
The invention will be further explained with reference to the drawings.
FIG. 1: schematic diagram for generating nano/submicron liquid drops by controllable induction liquid-liquid phase separation
FIG. 2: dynamic light scattering spectra of nanoscale droplets
FIG. 3: and (3) generating a transmission electron microscope picture of the hollow silicon dioxide nano structure by sodium citrate kosmotrope induced liquid-liquid phase separation synthesis.
FIG. 4: transmission electron microscope picture of gold-loaded nano-reactor and energy dispersion X-ray spectrogram of gold element
FIG. 5: ultraviolet-visible spectrum of adriamycin-loaded drug carrier and colorless picture of supernatant liquid of centrifuged product accumulated on bottom layer
FIG. 6: transmission electron microscopy picture (A) and powder X-ray color picture (B) of copper-based organic metal framework material HKUST-1 hollow nanostructure
FIG. 7: transmission electron microscopy of calcium phosphate hollow nanostructures
FIG. 8: transmission electron microscopy images of polydopamine hollow nanostructures
FIG. 9: transmission electron microscope picture of silicon dioxide hollow nanostructure synthesized by water-acetonitrile (A), water-dimethyl amide (B) and water-tetrahydrofuran system (C), and scale bar is 200 nm
FIG. 10: transmission electron microscope picture of glucose induced water-ethanol phase separation to generate nano liquid drop and synthesize hollow nano structure
FIG. 11: transmission electron microscope picture of sodium citrate inducing water-ethanol phase separation to generate hollow nano structure without thickener
Detailed Description
Example 1
Controllable induction liquid-liquid phase separation to generate nanometer/submicron-scale micro liquid drops:
to 95mL of an ethanol solution dissolved with 5mM citric acid and 1% by mass of hydroxypropyl cellulose (HPC) thickener, 5mL of deionized water was added, followed by 5mL of an ethanol solution dissolved with 0.36M sodium hydroxide (NaOH) under vigorous stirring. The dynamic light scattering pattern spectrum of the product shows droplets in nanometer/submicron size with a narrow size distribution. As shown in fig. 2.
Example 2
Reacting to generate sodium citrate kosmotrope inducing liquid-liquid phase separation to synthesize the hollow silicon dioxide nano structure:
to 95mL of an ethanol solution in which 5mM citric acid and 1% by mass of hydroxypropyl cellulose (HPC) were dissolved, 5mL of deionized water was added, and then 5mL of an ethanol solution in which 0.36M sodium hydroxide (NaOH) was dissolved was added under vigorous stirring. Then 0.6mL of Tetramethoxysilane (TEOS) was added. Then standing and reacting for 6 h. The product is washed by absolute ethyl alcohol and deionized water for many times, and the hollow silicon dioxide nano structure can be obtained. As shown in fig. 3, the hollow silica nano-architecture has better uniformity.
Example 3
Synthesis of gold-loaded nanoreactors:
this example pertains to the case where the compound to be supported is dissolved in a homogeneous mixed solvent. To 100mL of an ethanol solution dissolved with 10mM citric acid, 10mg/mL chloroauric acid, and 75mg/mL polyvinylpyrrolidone (PVP) thickener was added 5mL of deionized water, followed by 5mL of about 5M aqueous ammonia with vigorous stirring. Then 0.3mL TEOS was added and the reaction was allowed to stand for 10 hours. And washing the product with absolute ethyl alcohol and deionized water for multiple times to obtain the gold-loaded nano reactor. As shown in fig. 4, the loading of the gold nano-reactor was large, and a large amount of gold element signal was clearly seen.
Example 4
Synthesis of doxorubicin-loaded drug carriers
This example pertains to the case where the compound to be supported is added together with the kosmotrope in solution. To 100mL of an ethanol solution dissolved with 5mM citric acid and 1% by mass of HPC thickener, 50. mu.L of about 5M aqueous ammonia dissolved with 0.8mM doxorubicin was added with vigorous stirring. Then 0.15mL of Tetramethoxysilane (TEOS) was added. Standing and reacting for 10 hours. The product is washed by absolute ethyl alcohol for a plurality of times, and the nanometer hollow mesoporous silicon dioxide loaded with adriamycin can be obtained. As shown in fig. 5, the uv-vis spectrum shows the characteristic absorption of doxorubicin; the product collected on the colorless control of the supernatant after centrifugation, demonstrating that doxorubicin had been loaded onto the drug carrier, rather than free in solution.
Example 5
Synthesis of copper-based organic metal framework material HKUST-1 hollow nanostructure
To 100mL of an ethanol solution containing 1% by mass of HPC was added 15mL of an aqueous solution of 120mM copper sulfate and then 1mL of an ethanol solution of 80mM trimesic acid with vigorous stirring. The reaction system was closed and heated to 65 ℃ for 20 minutes. The product is washed by absolute ethyl alcohol and deionized water for many times, and the hollow nano-particles of the organic metal framework HKUST-1 material can be obtained. As shown in FIG. 6, the X-ray diffraction pattern confirmed that it was indeed HKUST-1.
Example 6
Synthesis of calcium phosphate hollow nanostructures
To 100mL of an ethanol solution in which 10mM phosphoric acid and 75mg/mL of polyvinylpyrrolidone (PVP) thickener were dissolved, 5mL of about 5M aqueous ammonia was added with vigorous stirring. Then, 5mL of a 1M ethanol solution of calcium chloride was added, and the mixture was allowed to stand for 30 minutes. The product is washed by absolute ethyl alcohol and deionized water for many times, and the calcium phosphate hollow nano particles can be obtained. As shown in fig. 7.
Example 7
Synthesis of polydopamine hollow nanostructure
To 95mL of an ethanol solution in which 10mM citric acid, 2mg/mL dopamine hydrochloride and 1% by mass of HPC were dissolved, 5mL of deionized water was added, followed by 5mL of about 5M aqueous ammonia under vigorous stirring. Then standing and reacting for 12 hours. And washing the product with absolute ethyl alcohol and deionized water for multiple times to obtain the polydopamine hollow nano-particles. As shown in fig. 8.
Example 8
The hollow silicon dioxide nanostructure synthesized by a water-acetonitrile, water-dimethyl amide and water-tetrahydrofuran system comprises the following components in percentage by weight:
this example demonstrates that controllably induced liquid-liquid phase separation can be applied in a wider range of homogeneous mixed solvent systems. To 95mL of acetonitrile, dimethylformamide and tetrahydrofuran solutions each containing 5mM citric acid and 1% by mass of Hydroxypropylcellulose (HPC) dissolved therein, 10mL of deionized water was added, and then 5mL of 2M ammonia in ethanol was added under vigorous stirring. Then 0.15mL of Tetramethoxysilane (TEOS) was added. Standing and reacting for 10 hours. And washing the product with absolute ethyl alcohol and deionized water for multiple times respectively to obtain respective silicon dioxide hollow nano structures. As shown in fig. 9.
Example 9
Glucose induces water-ethanol phase separation to generate nano liquid drops and synthesize hollow nano structure
In an ice-water bath, 100mL of an ethanol solution in which 3mM sodium hydroxide and 1% by mass of hydroxypropyl cellulose (HPC) were dissolved. 7.4mL of an aqueous solution of 2M glucose dissolved therein was added with vigorous stirring. Then 0.6mL of Tetramethoxysilane (TEOS) was added. Then standing and reacting for 6 hours in an ice water bath. The product is washed by absolute ethyl alcohol and deionized water for many times, and the hollow silicon dioxide nano structure can be obtained. As shown in fig. 10.
Example 10
Sodium citrate induces water-ethanol phase separation to generate hollow nano structure under the condition of no thickener
To 95mL of a solution of 5mM citric acid and 1% ethanol, 5mL of deionized water was added, followed by 5mL of an ethanol solution of 0.36M sodium hydroxide (NaOH) with vigorous stirring. Then 0.6mL of Tetramethoxysilane (TEOS) was added. Then standing and reacting for 6 h. The product is washed by absolute ethyl alcohol and deionized water for many times, and the hollow silicon dioxide nano structure can be obtained. As shown in fig. 11, it can be seen that the hollow nanostructures have irregular shapes, demonstrating the process of droplet fusion. It can be seen that tiny droplets can be generated and used to synthesize hollow nanostructures in the absence of a thickener, but thickeners can indeed improve the homogeneity of the product.
The invention is not limited to the specific technical solutions described in the above embodiments, and all technical solutions formed by equivalent substitutions are within the scope of the invention as claimed.
Claims (9)
1. A method for reliably synthesizing nano/submicron droplets by inducing liquid-liquid phase separation, characterized by comprising the steps of:
s1: the original system is a homogeneous mixed solvent system of mutually soluble water and an organic solvent, in particular to a mixture which only has one liquid phase and does not have split phase and is obtained by mixing two solvents which can be mutually soluble in any proportion;
s2: introducing a kosmotrope compound to enable the miscible liquid mixture which is originally one phase to be subjected to phase separation;
the kosmotrope refers to a substance which can enhance hydrogen bond network and/or intermolecular force in water, and refers to water-soluble salts or saccharides;
the kosmotrope can be directly added into a reaction system through a solution of water and/or an organic solvent; or may be produced by reaction;
s3: the phase separation process generates nano-sized fine droplets.
2. The method for reliably synthesizing nano/submicron droplets by inducing liquid-liquid phase separation according to claim 1, wherein the mixed solvent miscible at any ratio in step S1 comprises water-ethanol, water-n-propanol, water-isopropanol, water-tert-butanol, water-acetonitrile, water-dimethylformamide, water-tetrahydrofuran, water-acetone, or water-dimethylsulfoxide.
3. The method for reliably synthesizing nano/submicron liquid droplets by inducing liquid-liquid phase separation according to claim 1, wherein said kosmotrope compound in step S2 comprises sodium citrate, sodium oxalate, ammonium citrate, ammonium oxalate, sodium phosphate, ammonium phosphate, sodium sulfate, ammonium sulfate, copper sulfate, sodium trimesate, glucose, sucrose, or sodium polyacrylate.
4. The method for reliably synthesizing nano/submicron droplets by inducing liquid-liquid phase separation according to claim 1, wherein the kosmotrope is generated by reaction in step S2, and the salt is generated by neutralization by adding acid and alkali, respectively.
5. The method for the reliable synthesis of nano/submicron droplets by inducing liquid-liquid phase separation according to claim 1, characterized in that: the merging process of the fine droplets may also be suppressed to be more uniform by adding a thickener in step S1.
6. An application based on the method of claim 1, characterized in that: the method for reliably synthesizing nano/submicron droplets by inducing liquid-liquid phase separation is used for synthesizing hollow nanostructures, and the hollow nanostructures are generated by realizing in-situ micro-coating on the nanoscale micro liquid; the in situ micro-coating specifically refers to:
a. introducing raw materials which can react on the surface of the liquid drop to generate a solid shell material;
b. the liquid drops are coated in situ by the solid material shell generated by the raw materials to form the hollow nano structure.
7. Use of the method according to claim 6, characterized in that: the shell material in the step a and the raw materials corresponding to the shell material comprise silicon dioxide-tetramethoxysilane, silicon dioxide-tetraethoxysilane, silicon dioxide-tetrabutoxysilane, polydopamine-dopamine hydrochloride, polydopamine-dopamine oleate, calcium phosphate-calcium chloride, calcium phosphate-sodium phosphate, calcium phosphate-ammonium phosphate, organic metal framework HKUST-1-trimesic acid or organic metal framework HKUST-1-copper oleate.
8. Use of the method according to claim 6, characterized in that: the method for reliably synthesizing nano/submicron droplets by inducing liquid-liquid phase separation for synthesizing a nano reactor or a drug carrier comprises the following steps:
s1: adding the compound to be supported to the liquid-liquid mixture; the compound to be supported is a compound having catalytic properties in the case of a nanoreactor; and in the case of a drug carrier, a drug;
the addition of the compound to be loaded is divided into two cases:
a. dissolving the mixture in a homogeneous mixed solvent system before the reaction;
b. when the kosmotrope compound is introduced, the kosmotrope compound is added together with the kosmotrope compound dissolved in the kosmotrope compound;
s2: generating micro liquid drops containing the compound to be loaded inside;
s3: and micro-coating the liquid drops to obtain a hollow nano structure containing a compound to be loaded, a nano reactor or a drug carrier.
9. Use of the method according to any of claims 6-8, characterized in that: the method for reliably synthesizing nano/submicron droplets by inducing liquid-liquid phase separation is used for synthesizing a nano reactor and a drug carrier, and the process of loading a compound to be loaded and the process of generating a hollow nano structure are synchronously completed in one reaction.
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