CN115073764A - Liquid metal microgel and preparation method and application thereof - Google Patents

Abstract

The invention relates to the field of micro-nano materials, in particular to a liquid metal microgel and a preparation method and application thereof. The liquid metal microgel of the present invention includes an inner core and a shell layer; the inner core is a micro-nano-scale liquid metal particle, and the shell layer is a gel layer; wherein the gel layer is made of a polymer material in a liquid state. formed in situ on the surface of metal particles. The liquid metal microgel obtained by the invention not only has the original advantages of the microgel, but also has the characteristics of the liquid metal, shows the complementary advantages of the microgel and the liquid metal, has more abundant functions, and can be used in various biomedical applications. fields (including drug carriers, molecular imaging, cancer treatment and biomedical devices) and physical chemistry or coatings show broad development potential.

Description

A kind of liquid metal microgel and its preparation method and application

technical field

The invention belongs to the field of micro-nano materials, in particular to a liquid metal microgel and a preparation method and application thereof.

Background technique

Microgel is a new type of functional polymer with a size between 1 and 1000 nm and an intramolecular cross-linked structure. Due to a series of performance advantages, such as high specific surface area, modifiability, mechanical strength, permeability, electrophoretic mobility, bulk phase transition behavior, etc., microgels have been used more and more widely.

The synthesis of microgels requires certain technical means and processes to form an ordered structure with specific functions. The key is to avoid cross-linking between polymer chains as much as possible and control the cross-linking within the polymer chains.

Traditional preparation methods include emulsion polymerization, solution polymerization, suspension polymerization, precipitation polymerization, microemulsion polymerization, and the like. Among them, the most common and effective methods are emulsion polymerization and solution polymerization.

Emulsion polymerization relies on emulsifiers to isolate monomers, cross-linking agents, initiators, etc. inside the microemulsion droplets, which is equivalent to limiting the spatial size of the reaction system, so that microgels can be formed by monomer cross-linking. However, the addition of emulsifier increases the difficulty for subsequent purification, and also has a certain impact on the performance of microgels.

Solution polymerization forms microgels by diluting the monomer concentration in the solution so that the probability of intermolecular crosslinking is much lower than that of intramolecular crosslinking. Although this preparation method is simple, it usually requires a large amount of solvent and is relatively inefficient.

In addition, the microgels prepared by these methods have a single function and are difficult to match with complex application requirements. For this reason, a facile method to prepare microgels with rich functions is urgently needed.

SUMMARY OF THE INVENTION

A first aspect of the present invention provides a liquid metal microgel. The microgel has rich functions and a simple preparation method.

The liquid metal microgel of the present invention includes an inner core and a shell layer; the inner core is a micro-nano-scale liquid metal particle, and the shell layer is a gel layer; wherein the gel layer is made of polymer materials in a liquid state. formed in situ on the surface of metal particles.

The liquid metal microgel obtained by the invention not only has the original advantages of the microgel, such as high specific surface area, modifiability, mechanical strength, permeability, electrophoretic migration ability, volume phase transition behavior, etc., but also has the characteristics of liquid metal, Such as excellent fluidity, excellent flexibility, shape deformability and low viscosity, etc., showing the complementary advantages of microgels and liquid metals, with richer functions, which can be used in various fields of biomedical applications (including pharmaceuticals) vector, molecular imaging, cancer therapy and biomedical devices) show broad development potential.

The size of the liquid metal microgel of the present invention can be determined according to actual needs. For example, the diameter of the liquid metal particles ranges from 10 to 1000 nm; the thickness of the gel layer ranges from 1 to 500 nm. Studies have shown that the size relationship between the diameter of the inner core and the thickness of the shell is related to the release rate of metal ions from liquid metal and the diffusion rate of metal ions in the gel material. The size relationship is regulated by means of pH value, applied electric field, etc.

However, in actual use, there is a certain match between the diameter of the liquid metal particles and the thickness of the gel layer, and the obtained liquid metal microgel has more practical significance. Preferably, the size ratio of the diameter of the inner core to the thickness of the shell should be between 1:10 and 10:1. Studies have shown that if the ratio is too large, it means that the size of the liquid metal particles is relatively large, and the encapsulation effect of the gel layer is not good; if the ratio is too small, it means that the gel layer is relatively thick, and the effect of the liquid metal cannot be fully exerted. Controlling the ratio of the two within the above range is more conducive to the complementary advantages of the liquid metal microgel.

As one of the specific embodiments, when the liquid metal microgel is used as a drug carrier, the smaller the ratio, the thicker the gel layer, which is more favorable for drug loading. For example, the diameter of the inner core and the shell layer The dimension ratio of the thickness should be between 1:10 and 1:1.

As another specific embodiment, when the liquid metal microgel is used for magnetocaloric, a larger proportion means a relatively larger size of the liquid metal particles, which is more favorable for magnetocaloric properties, for example, the diameter of the inner core is the same as that of the The dimensional ratio of the thickness of the shell should be between 1:1 and 10:1.

The polymer material of the present invention is protein and/or polysaccharide.

The protein may be one or more of soy protein isolate, whey protein isolate, and the like.

The polysaccharide can be one or more of sodium alginate, hyaluronic acid, sodium carboxymethyl cellulose, quaternized chitosan, fructose or pectin.

The specific selection of the polymer material can be determined according to the specific application requirements of the microgel.

The liquid metal described in the present invention is a metal or alloy that is in a liquid state when the temperature is lower than 30° C. The alloy is a gallium indium alloy, a gallium indium tin alloy, a gallium indium tin zinc alloy, a gallium indium tin zinc bismuth alloy or a doped gallium indium tin alloy. One of the aforementioned alloys of nanomaterials; the specificity can be determined according to the specific use requirements of the microgel.

A second aspect of the present invention provides a method for preparing a liquid metal microgel, comprising:

The liquid metal is added to the solution containing the polymer material, and the micro-nano-scale liquid metal particles are obtained as the inner core through the crushing treatment, and the metal ions are released at the same time;

Using metal ions as the cross-linking agent, the polymer material is in-situ cross-linked on the surface of the liquid metal particles to obtain a gel layer as the shell layer.

Aiming at the defects of the existing microgel preparation methods, the present invention proposes to utilize the characteristics of liquid metal to release metal ions, use metal ions as cross-linking agent, and control the release of the cross-linking agent to make the polymerization/cross-linking reaction of polymer materials. occurs at specific regions inside the composite microgels, thereby preparing hybrid microgels in situ.

Specifically, the present invention utilizes the soft properties of liquid metal to obtain micro/nano-scale liquid metal particles; during the preparation process of liquid metal particles, the thin oxide "film" on the surface of liquid metal (similar to the aluminum oxide protection of metal aluminum coating) is rapidly destroyed, and liquid metal ions are released due to the active chemical properties, thereby in situ crosslinking with the crosslinkable polymer material to form a microgel.

In the present invention, the crushing treatment can be realized by ultrasonic method, model method, mechanical stirring method or microfluidic focusing method; ultrasonic method is preferred; compared with other treatment processes, ultrasonic method has the advantages of being simpler and faster. The time of the crushing treatment is 10-100 min, which can be determined according to the actual particle size requirements.

In the present invention, the concentration of the polymer material in the solution is related to the thickness of the finally formed gel layer, and the concentration range of the polymer material solution can be 1-30 wt % to meet different usage requirements. The solvent of the solution is one of water, ethanol, acetone, ethylene glycol or trichloroethane.

In order to obtain a microgel with better matching, as one of the specific embodiments of the present invention, when the crushing treatment is an ultrasonic method, the mass concentration of the polymer material solution is 8-12%, and the ultrasonic conditions For power 65-75%, time 18-22min. The research shows that under the condition of this range, the obtained liquid metal microgel has the advantages of more uniform shape and more uniform size distribution.

Further research of the present invention shows that the size relationship between the inner core diameter of the liquid metal microgel and the thickness of the shell layer is related to the release rate of metal ions from the liquid metal and the diffusion rate of metal ions in the gel material, so it can be adjusted by adjusting the liquid metal The size relationship is regulated by crushing method, polymer material concentration, pH value, and applied electric field.

The preparation method of the present invention also includes post-treatment; the post-treatment includes washing and centrifugation of the crude product; and the obtained microgel can be stored for a long time after being lyophilized.

The washing solution used in the washing is one or more of neutral buffer solution, absolute ethanol or deionized water.

The third aspect of the present invention provides the application of the above-mentioned liquid metal microgel in the fields of biomedicine, physical chemistry, and coating.

For biomedicine, the liquid metal microgel of the present invention can realize CT imaging, MRI imaging, drug loading, active oxygen generation, thermal conversion, magnetism, embolization, electrical conductivity, thermal conductivity and other functions, and can be used in medical imaging, biological transmission and other functions. Sensitivity, targeted drug release carrier, cold therapy, hyperthermia, photodynamic therapy, interventional therapy, etc.

For physical and chemical aspects, the liquid metal microgel of the present invention can play a role in physical adsorption, catalysis, micro-reactor and the like.

For the coating field, the liquid metal microgel of the present invention can play a role in pigments, thermal conductive coatings, conductive coatings and the like.

The beneficial effects of the present invention are:

The liquid metal microgel proposed by the present invention can realize functions such as CT imaging, MRI imaging, drug loading, active oxygen generation, thermal conversion, magnetism, embolization, electrical conductivity, thermal conductivity, etc., and is expected to be applied to biomedicine (such as medical imaging, biosensing , targeted drug release carrier, cold therapy, hyperthermia, photodynamic therapy, interventional therapy, etc.), physical chemistry (such as physical adsorption, catalysis, microreactor, etc.), and coatings (such as pigments, thermal conductive coatings, conductive coatings, etc.) and other fields. Meanwhile, the preparation method of the liquid metal microgel has the advantages of being more rapid and convenient. In a word, the liquid metal microgel of the present invention solves the defects of single function and complicated preparation process of the existing microgel, and achieves remarkable technical effect.

Description of drawings

1 is a schematic diagram of the preparation method of the liquid metal alginic acid nanogel material in Example 1.

FIG. 2 is a transmission electron microscope image of the liquid metal alginic acid nanogel material in Example 1. FIG.

FIG. 3 is an image of the biocompatibility of the liquid metal alginic acid nanogel material in Example 1. FIG.

FIG. 4 is a CT imaging image of the liquid metal alginic acid nanogel material in Example 1. FIG.

5 is an image of the photothermal properties of the liquid metal alginic acid nanogel material in Example 1.

FIG. 6 is an image of the magnetocaloric properties of the liquid metal alginic acid nanogel material in Example 1. FIG.

7 is a transmission electron microscope image of the liquid metal nanomaterial in Comparative Example 1.

Detailed ways

The following examples are intended to illustrate the present invention, but not to limit the scope of the present invention.

The raw materials and instruments used in the examples have no specific restrictions on their sources, and can be purchased in the market or prepared according to conventional methods well known to those skilled in the art.

The liquid metal in the raw material is prepared according to the following technical scheme, taking Ga _75.5 In _24.5 as an example:

(a) Weigh metal gallium and indium with a purity of 99.9%, and take out the corresponding mass of liquid metal gallium and put it into a beaker according to the mass ratio of 74.5:24.5;

(b) place the beaker on a heating constant temperature magnetic stirrer, set the heating temperature to 80°C, and set the rotation speed to 200r/min, and then add the weighed indium block to the beaker;

(c) After the indium block is dissolved, two magnetic stirring bars are added to the liquid metal, and the metal liquid is stirred for 10 min to make it a homogeneous phase.

The alloys of Ga ₉₀ In ₁₀ , Ga ₈₀ In ₂₀ , Ga ₇₀ In ₃₀ and Ga ₆₀ In ₄₀ can be prepared by changing the mass ratio of metal gallium and indium by the same operation.

Example 1

The present embodiment is a preparation method of a liquid metal alginic acid microgel, which specifically includes the following steps:

Put an appropriate amount of liquid metal (Ga) into a sodium alginate solution with a mass concentration of 10%, and use an ultrasonic method (ultrasonic breaker, Emerson, ultrasonic power 70%, time 20min) to prepare a liquid metal nanogel material, deionized Washed with water for more than 3 times and collected after lyophilization.

The working principle is as follows: During the ultrasonic process, the oxide film on the surface of the liquid metal is ruptured, broken into nanoparticles, and chemically active gallium is exposed at the same time; since the cross-linking of alginic acid and metal ions can form a gel, the surface of the liquid metal releases gallium ions Gels can be formed in situ with sodium alginate.

The flow chart of the operation of this embodiment is shown in FIG. 1 , and the finally obtained liquid metal alginic acid nanogel material is shown in FIG. 2 .

Performance tests show that the liquid metal microgel has good drug-carrying capacity, and the drug-carrying capacity and encapsulation efficiency reach 5-10% and 30-50% respectively.

Meanwhile, cell proliferation assays showed that these microgels did not affect cell proliferation, showing excellent biocompatibility, as shown in Figure 3.

In addition, the microgels retain the imaging ability, photothermal, and magnetocaloric properties of liquid metals, as shown in Figures 4-6.

Example 2

The difference between this embodiment and Embodiment 1 is only that the Ga liquid metal in Embodiment 1 is replaced with Ga _74.5 In _24.5 liquid metal (melting point 15.7° C.).

The test results show that a fully flexible liquid metal alginate nanogel material at room temperature is prepared in this example, and other properties are similar to those of Example 1.

Example 3

The difference between this embodiment and Embodiment 1 is only that the Ga liquid metal in Embodiment 1 is replaced with a magnetic liquid metal doped with iron nanoparticles (magnetic Ga _75.5 In _24.5 ).

Note: Preparation method of magnetic liquid metal: take 2g of iron nanoparticles and evenly disperse them at the bottom of the beaker, take 10g of liquid metal (Ga _75.5 In _24.5 ) drop by drop into the beaker, and let the surface of the liquid metal be fully coated with iron nanoparticles; then Concentrated hydrochloric acid with a concentration of 36-37 wt % is dropped on the surface of the liquid metal coated with iron nanoparticles to prepare a magnetic liquid metal.

The test results show that the liquid metal alginic acid nanogel material prepared in this example has magnetic properties.

Example 4

The difference between this embodiment and Embodiment 1 is only that the ultrasonic crushing method in Embodiment 1 is replaced with a method with a weaker crushing force, such as a magnetic stirrer.

The test results show that the liquid metal alginic acid microgel material is prepared in this example.

Example 5

The only difference between this example and Example 1 is that the sodium alginate solution in Example 1 is replaced with an aqueous pectin solution.

The test results show that the liquid metal pectin nanogel material is prepared in this example.

Example 6

The only difference between this example and Example 1 is that the sodium alginate solution in Example 1 is mixed with magnetic ferric ferric oxide particles, and during the gel formation process, the magnetic particles will be encapsulated inside the gel.

The test results show that the liquid metal alginic acid nanogel material wrapped with magnetic particles is prepared in this example.

In addition, other properties of the liquid metal microgels obtained in Examples 2-6 were similar to those in Example 1.

Comparative Example 1

The difference between the preparation method provided in this comparative example and Example 1 is only that the sodium alginate solution is replaced with a polyethylene glycol solution, that is, a gel-free polymer material.

As a result, as shown in Fig. 7, a single spherical liquid metal particle was obtained, and no gel was formed on its surface.

Although the present invention has been described in detail above with general description and specific embodiments, it is obvious to those skilled in the art that some modifications or improvements can be made on the basis of the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention fall within the scope of the claimed protection of the present invention.

Claims (10)

1. a liquid metal microgel, is characterized in that, comprises inner core and shell layer; Described inner core is the liquid metal particle of micro-nano level, and described shell layer is gel layer; Described gel layer is made of macromolecule. The material is formed in situ on the surface of the liquid metal particles. 2 . The liquid metal microgel according to claim 1 , wherein the size ratio of the diameter of the inner core to the thickness of the shell layer should be between 1:10 and 10:1. 3 . 3. The liquid metal microgel according to claim 1 or 2, wherein the polymer material is protein and/or polysaccharide; Preferably, the protein is soy protein isolate and/or whey protein isolate; Preferably, the polysaccharide is one or more of sodium alginate, hyaluronic acid, sodium carboxymethylcellulose, quaternized chitosan, fructose or pectin. 4. The liquid metal microgel according to claim 3, wherein the liquid metal is a metal or alloy that exhibits a liquid state when the temperature is lower than 30 degrees Celsius; Preferably, the alloy is one of gallium indium alloy, gallium indium tin alloy, gallium indium tin zinc alloy, gallium indium tin zinc bismuth alloy, or one of the aforementioned liquid metals doped with nanomaterials. 5. the preparation method of the described liquid metal microgel of any one of claim 1-4, is characterized in that, comprises: The liquid metal is added to the solution containing the polymer material, and the micro-nano-scale liquid metal particles are obtained as the inner core through the crushing treatment, and the metal ions are released at the same time; Using metal ions as the cross-linking agent, the polymer material is in-situ cross-linked on the surface of the liquid metal particles to obtain a gel layer as a shell layer. 6 . The preparation method of the liquid metal microgel according to claim 5 , wherein the crushing treatment is realized by an ultrasonic method, a model method, a mechanical stirring method or a microfluidic focusing method. 7 . 7 . The method for preparing the liquid metal microgel according to claim 5 or 6 , wherein the concentration range of the polymer material solution is 1-30 wt %. 8 . 8 . The preparation method of the liquid metal microgel according to claim 7 , wherein when the crushing treatment is an ultrasonic method, the mass concentration of the polymer material solution is 8-12%, and the Ultrasound conditions are power 65-75%, time 18-22min. 9. Application of the liquid metal microgel according to any one of claims 1-4 in the fields of biomedicine, physical chemistry or coating. 10. The application according to claim 9, wherein the liquid metal microgel is used in medical imaging, biosensing, targeted drug release carrier, cold therapy, hyperthermia, photodynamic therapy or interventional therapy. application; or, the application of the liquid metal microgel in a physical adsorption, catalytic or microscopic reactor; or, The application of the liquid metal microgel in pigment, thermal conductive coating or conductive coating.

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