阅读说明：本技术 一种自驱动型人工智能材料、制备方法与在成像分析检测及药物控释中的应用 (Self-driven artificial intelligence material, preparation method and application in imaging analysis and detection and drug controlled release ) 是由 蒋刚彪 李曾林 胡甜 刘永林 胡汉剑 于 2019-08-20 设计创作，主要内容包括：本发明公开了一种自驱动型人工智能材料、制备方法与在成像分析检测及药物控释中的应用。本发明采用壳聚糖和羧甲基壳聚糖为基底,包裹表面活性剂并还原氯金酸,制备纳米金自驱动型人工智能材料。由于材料的自驱动性使其能顺利进入传统材料达不到的位置,加上纳米金易于化学修饰又具有良好的生物相容性、优异的生物惰性、表面等离子共振特性等,制备的这种自驱动型人工智能材料在成像、分析传感、检测和药物定点输送等领域有很好的应用前景。(The invention discloses a self-driven artificial intelligence material, a preparation method and application in imaging analysis and detection and drug controlled release. The invention adopts chitosan and carboxymethyl chitosan as substrates, coats a surfactant and reduces chloroauric acid to prepare the nano-gold self-driven artificial intelligence material. The self-driven type artificial intelligent material can smoothly enter a position which cannot be reached by the traditional material due to the self-driving property of the material, and the nano-gold is easy to chemically modify and has good biocompatibility, excellent biological inertia, surface plasma resonance characteristics and the like.)

1. A preparation method of a self-driven artificial intelligence material is characterized by comprising the following steps:

(1) dissolving disodium ethylene diamine tetraacetate in water, stirring uniformly, adding FeCl₃·6H₂O, mixing evenly to obtain EDTA-Fe³⁺A solution; dissolving chitosan in an acetic acid aqueous solution, and uniformly stirring to obtain a chitosan acetic acid aqueous solution;

(2) adding chloroauric acid into chitosan acetic acid aqueous solution, stirring uniformly, adding a surfactant, heating to 60-100 ℃, adding trisodium citrate, reacting for 0.5-3 h, finishing the reaction, cooling to room temperature, adding EDTA-Fe³⁺After uniformly mixing the solution, adding carboxymethyl chitosan, and uniformly mixing to obtain nanogold hydrogel;

(3) introducing the nanogold hydrogel into a mold for molding, and freeze-drying to obtain aerogel;

(4) and (3) introducing the aerogel into a mold, adding the nanogold hydrogel, and taking out after molding to obtain the self-driven artificial intelligence material consisting of the hydrogel and the aerogel, wherein the surface of the hydrogel part is coated with silicone grease.

2. The method for preparing a self-driven artificial intelligence material according to claim 1, wherein the chitosan, chloroauric acid, surfactant, trisodium citrate, EDTA-Fe in the chitosan-acetic acid aqueous solution of step (2)³⁺EDTA-Fe in solution³⁺And carboxymethyl chitosan in a mass ratio of: (0.1E0.45)：(0.00004～0.0015)：(0.06～0.8)：(0.001～0.04)：(0.035～1)：(0.3～2.5)。

3. The method for preparing a self-driven artificial intelligence material according to claim 1 or 2, wherein the disodium salt of ethylenediaminetetraacetic acid and FeCl are used in the step (1)₃·6H₂The mass ratio of O is (0.2-3): (0.5 to 7); the volume ratio of the aerogel to the hydrogel in the step (4) is (2-3): (1-2).

4. The method for preparing a self-driven artificial intelligence material according to claim 3, wherein the EDTA-Fe of step (1)³⁺The mass concentration of the disodium ethylene diamine tetraacetate in the solution is 0.2-3 g/100ml of water, and the EDTA-Fe³⁺FeCl in solution₃·6H₂The mass concentration of O is 0.5-7 g/100ml of water; the mass concentration of the chitosan in the acetic acid water solution is 1-3 g/100ml of water;

adding chloroauric acid in the step (2) in the form of a chloroauric acid aqueous solution, wherein the mass concentration of the chloroauric acid aqueous solution is 0.01-0.1 g/100ml of water; the surfactant is added in the form of a surfactant aqueous solution, and the mass concentration of the surfactant is 2-10 g/100ml of water; the trisodium citrate is added in the form of a trisodium citrate water solution, and the mass concentration of the trisodium citrate is 0.5-5 g/100ml of water; the carboxymethyl chitosan is added in the form of a carboxymethyl chitosan aqueous solution, and the mass concentration of the carboxymethyl chitosan is 2-10 g/100ml of water.

5. The method of claim 4, wherein the chitosan-acetic acid aqueous solution, chloroauric acid aqueous solution, surfactant aqueous solution, trisodium citrate aqueous solution, EDTA-Fe³⁺The volume ratio of the solution to the carboxymethyl chitosan aqueous solution is as follows: (10-15): (0.4-1.5): (3-8): (0.2-0.8): (5-10): (15-25).

6. The method for preparing a self-driven artificial intelligence material according to claim 4, wherein the volume concentration of acetic acid in the aqueous acetic acid solution of step (1) is 0.8 to 1.5ml/100ml of water; and (3) the surfactant in the step (2) is at least one of sodium dodecyl sulfate, cetyl trimethyl ammonium bromide and tween 20.

7. The method for preparing the self-driven artificial intelligence material according to claim 5, wherein the aqueous solution of the surfactant is prepared by adding the surfactant into water and stirring at room temperature for 0.5-1 h;

the carboxymethyl chitosan aqueous solution is prepared by the following method: adding carboxymethyl chitosan into water, and stirring for 4-12 h at room temperature;

and (4) forming, namely, the nanogold hydrogel is adaptive to a mold after 10-60 min under natural conditions to form the hydrogel with the shape fixed by the mold.

8. The method for preparing a self-driven artificial intelligence material according to claim 4, wherein the conditions of dissolving the disodium salt of ethylenediaminetetraacetic acid in water and stirring uniformly in step (1) are as follows: stirring for 0.5-2 h at room temperature; the conditions for uniform mixing are as follows: stirring for 1-3 h at room temperature; the chitosan is dissolved in the acetic acid water solution and then is uniformly stirred under the following conditions: stirring for 6-24 h at room temperature;

adding EDTA-Fe in the step (2)³⁺The conditions for mixing the solution uniformly are as follows: stirring for 0.5-1.5 h at room temperature; the conditions for uniformly mixing after adding the carboxymethyl chitosan are as follows: 0.5-1.5 h at room temperature; the condition of uniformly stirring after adding the chloroauric acid is that stirring is carried out for 10-40 min at room temperature;

the moulds in the steps (3) and (4) are discs with the diameter of 10mm and the thickness of 5 mm; the freeze drying conditions in the step (3) are as follows: freeze drying at-80 deg.c for 8-14 hr.

9. A self-driven type artificial intelligence material produced by the method according to any one of claims 1 to 8.

10. Use of a self-driven artificial intelligence material according to claim 9 in the fields of imaging, analytical sensing, detection and site-specific drug delivery.

Technical Field

The invention belongs to the field of intelligent high polymer materials, and particularly relates to a self-driven artificial intelligent material, a preparation method and application in imaging analysis and detection and drug controlled release.

Background

The self-driven artificial intelligence material has attracted wide attention in the fields of drug delivery, analytical sensing, environmental management and the like due to the characteristic of autonomous motion. At present, the self-driving material is mostly a tubular or spherical Janus micromotor with a multilayer metal structure consisting of Ti, Fe, Au, Ag, Pt and the like, and the propulsion power is provided based on the generation of bubbles through the decomposition of catalytic hydrogen peroxide. Although the micro motor has small volume and high movement speed, the micro motor has high requirements on the external environment, can only move in hydrogen peroxide solution, is complicated in preparation method, is mostly prepared by methods such as sputtering coating, photoetching and electrochemical deposition, and greatly limits the development of the micro motor in practical application. Therefore, it is necessary to search for a self-driving material which is simple to prepare and has good self-adaptability.

The hydrogel serving as a soft material with a three-dimensional network structure has solid viscoelasticity, good deformability and strong encapsulation property, and also has liquid diffusivity, the water-soluble small molecules can be freely diffused through the three-dimensional network structure, and the preparation method is simple. The hydrogel prepared from the natural polysaccharide chitosan has the characteristics of good biocompatibility, no toxicity, good flexibility and strong encapsulation property, and is a self-driven preparation material with great potential.

Disclosure of Invention

In order to overcome the defects and shortcomings in the prior art, the invention aims to provide a preparation method of a self-driven artificial intelligence material. The nano-gold self-driven artificial intelligence material is prepared by adopting chitosan and carboxymethyl chitosan as substrates, wrapping a surfactant and reducing chloroauric acid.

Another object of the present invention is to provide a self-driven type artificial intelligence material manufactured by the above method.

It is still another object of the present invention to provide the use of the above-mentioned self-driven artificial intelligence material in the fields of imaging, analytical sensing, detection and site-specific drug delivery.

The self-driven type artificial intelligent material can smoothly enter a position which cannot be reached by the traditional material due to the self-driving property of the material, and the nano-gold is easy to chemically modify and has good biocompatibility, excellent biological inertia, surface plasma resonance characteristics and the like.

The purpose of the invention is realized by the following technical scheme:

a preparation method of a self-driven artificial intelligence material comprises the following steps:

(1) dissolving disodium ethylene diamine tetraacetate (EDTA-disodium) in water, stirring well, adding FeCl₃·6H₂O, mixing evenly to obtain EDTA-Fe³⁺A solution; dissolving chitosan in an acetic acid aqueous solution, and uniformly stirring to obtain a chitosan acetic acid aqueous solution;

(2) adding chloroauric acid into chitosan acetic acid aqueous solution, stirring uniformly, adding a surfactant, heating to 60-100 ℃, adding trisodium citrate, reacting for 0.5-3 h, finishing the reaction, cooling to room temperature, adding EDTA-Fe³⁺After uniformly mixing the solution, adding carboxymethyl chitosan, and uniformly mixing to obtain nanogold hydrogel;

(3) introducing the nanogold hydrogel into a mold for molding, and freeze-drying to obtain aerogel;

(4) and (3) introducing the aerogel into a mold, adding the nanogold hydrogel, and taking out after molding to obtain the self-driven artificial intelligence material consisting of the hydrogel and the aerogel, wherein the surface of the hydrogel part is coated with silicone grease.

Step (1)) The ethylene diamine tetraacetic acid disodium salt and FeCl₃·6H₂The mass ratio of O is (0.2-3): (0.5 to 7). The EDTA-Fe³⁺The mass concentration of the disodium ethylene diamine tetraacetate in the solution is 0.2-3 g/100ml of water, and the EDTA-Fe³⁺FeCl in solution₃·6H₂The mass concentration of O is 0.5-7 g/100ml of water.

Dissolving the disodium ethylene diamine tetraacetate of the step (1) in water and then uniformly stirring the solution under the following conditions: stirring for 0.5-2 h at room temperature; the conditions for uniform mixing are as follows: stirring for 1-3 h at room temperature.

The mass concentration of the chitosan in the acetic acid water solution in the step (1) is 1-3 g/100ml of water; the volume concentration of acetic acid in the acetic acid water solution is 0.8-1.5 ml/100ml of water; the chitosan is dissolved in the acetic acid water solution and then is uniformly stirred under the following conditions: stirring for 6-24 h at room temperature.

The chitosan acetic acid aqueous solution in the step (1) needs to be stored at low temperature, preferably at 4 ℃.

Chitosan, chloroauric acid, surfactant, trisodium citrate and EDTA-Fe in the chitosan acetic acid aqueous solution in the step (2)³⁺EDTA-Fe in solution³⁺And carboxymethyl chitosan in a mass ratio of: (0.1-0.45): (0.00004-0.0015): (0.06-0.8): (0.001-0.04): (0.035-1): (0.3-2.5).

The chloroauric acid in the step (2) is preferably added in the form of a chloroauric acid aqueous solution, and the mass concentration of the chloroauric acid aqueous solution is 0.01-0.1 g/100ml of water. The aqueous chloroauric acid solution is obtained by dissolving chloroauric acid in water.

And (3) the surfactant in the step (2) is at least one of Sodium Dodecyl Sulfate (SDS), Cetyl Trimethyl Ammonium Bromide (CTAB) and tween 20. The surfactant is preferably added in the form of a surfactant aqueous solution, and the mass concentration of the surfactant aqueous solution is 2-10 g/100ml of water. The surfactant aqueous solution is obtained by adding a surfactant into water and stirring at room temperature for 0.5-1 h.

The trisodium citrate in the step (2) is preferably added in the form of a trisodium citrate water solution, and the mass concentration of the trisodium citrate water solution is 0.5-5 g/100 ml. The aqueous solution of trisodium citrate is obtained by dissolving trisodium citrate in water.

The carboxymethyl chitosan in the step (2) is preferably added in the form of a carboxymethyl chitosan aqueous solution, and the mass concentration of the carboxymethyl chitosan aqueous solution is 2-10 g/100ml of water. The carboxymethyl chitosan aqueous solution is prepared by the following method: adding carboxymethyl chitosan into water, and stirring for 4-12 h at room temperature. The carboxymethyl chitosan aqueous solution needs to be stored at low temperature, preferably at 4 ℃.

The condition of adding chloroauric acid and then uniformly stirring in the step (2) is as follows: stirring for 10-40 min at room temperature. Said addition of EDTA-Fe³⁺The conditions for mixing the solution uniformly are as follows: stirring for 0.5-1.5 h at room temperature. The conditions for uniformly mixing after adding the carboxymethyl chitosan are as follows: stirring for 0.5-1.5 h at room temperature.

The chitosan acetic acid aqueous solution, the chloroauric acid aqueous solution, the surfactant aqueous solution, the trisodium citrate aqueous solution and EDTA-Fe³⁺The volume ratio of the solution to the carboxymethyl chitosan aqueous solution is as follows: (10-15): (0.4-1.5): (3-8): (0.2-0.8): (5-10): (15-25).

The shapes of the moulds in the steps (3) and (4) are not limited, and the moulds are preferably discs, more preferably discs with the diameters of 10mm and the thicknesses of 5 mm; the forming refers to that the nanogold hydrogel is adaptive to a mold after 10-60 min under natural conditions to form the hydrogel with the shape fixed by the mold.

The freeze drying conditions in the step (3) are as follows: freeze drying at-80 deg.c for 8-14 hr.

The volume ratio of the aerogel to the hydrogel in the step (4) is (2-3): (1-2).

And (4) uniformly coating the silicone grease on the surface of the hydrogel.

Before use, the self-driven artificial intelligence material in the step (4) is soaked in the surfactant aqueous solution in the step (2), so that the motion effect is better.

The self-driven artificial intelligence material is prepared by the method.

The self-driven artificial intelligence material is applied to the fields of imaging, analytical sensing, detection and fixed-point drug delivery.

Chitosan in the raw materials used in the present applicationThe gold chloride acid and trisodium citrate can be reduced into gold nanoparticles, chitosan amino protonation positive charge can well wrap the gold nanoparticles under the acidic condition, and the surfactant added in the gold chloride acid reduction process can not only stabilize the gold nanoparticles and regulate and control the particle size and morphology, but also serve as a self-driving fuel in the subsequent use process. The chitosan is wrapped by the nano-gold, and has physical winding and hydrogen bonding action with the carboxymethyl chitosan, and the carboxymethyl chitosan and EDTA-Fe³⁺And coordination chelation exists between the two groups, so that a stable double-network structure can be formed. The self-driven artificial intelligent material prepared finally has good self-deformation capability; has low requirement on external environment, and can move well in water, glucose solution, acidic and alkaline solutions. When the hydrogel is contacted with aqueous solution, the encapsulated surfactant can be slowly released, the aerogel is quickly released, and the hydrogel is slowly released after being coated with silicone grease, so that the local surface tension of the solution is reduced to generate movement.

Compared with the prior art, the invention has the following advantages and beneficial effects:

(1) compared with the self-driven material prepared from an inorganic metal material, the self-driven material prepared from chitosan and carboxymethyl chitosan has better biocompatibility and adaptivity; the prepared self-driven material has a double-gel network, has a stable structure and can be recycled.

(2) Compared with a motor which can only move in a hydrogen peroxide solution or a glucose solution, the self-driving material prepared by the invention can move well in water, the glucose solution, an acidic solution and an alkaline solution, and can slowly release the coated surfactant when contacting the aqueous solution, so that the local surface tension of the solution is reduced and the solution moves.

(3) The invention firstly adopts the mode of combining hydrogel and aerogel to prepare the self-driven artificial intelligent material, and lays a good foundation for the development of intelligent high polymer materials in the fields of imaging, analytical sensing, detection, fixed-point drug delivery and the like.

Drawings

FIG. 1 is a scanning electron micrograph of a aerogel in the self-driven type artificial intelligence material prepared in example 1, which is magnified 200 times.

FIG. 2 is a transmission electron micrograph of the self-driven type artificial intelligence material prepared in example 1.

Fig. 3 is a drug release profile of the drug-loaded self-driving artificial intelligence material prepared in example 8.

Fig. 4 is a graph showing the moving speed of the self-driven type artificial intelligence material in deionized water and hydrochloric acid solutions having pH 2 and pH 5 in example 9.

FIG. 5 is a graph showing the moving speed of the self-driven type artificial intelligence material in example 9 in a deionized water solution containing an agar block of hydrochloric acid.

Detailed Description

The present invention will be described in further detail with reference to examples and drawings, but the embodiments of the present invention are not limited thereto.

In the embodiment of the application, the moulds are all circular discs with the diameter of 10mm and the thickness of 5 mm. The aqueous chloroauric acid solution is obtained by dissolving chloroauric acid in water. The aqueous solution of trisodium citrate is obtained by dissolving trisodium citrate in water.