CN113117076B - Preparation method of gel gold nanocluster compound, compound and application - Google Patents

Preparation method of gel gold nanocluster compound, compound and application Download PDF

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CN113117076B
CN113117076B CN202010045274.8A CN202010045274A CN113117076B CN 113117076 B CN113117076 B CN 113117076B CN 202010045274 A CN202010045274 A CN 202010045274A CN 113117076 B CN113117076 B CN 113117076B
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gel gold
gel
polysaccharide polymer
natural polysaccharide
gold nanocluster
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CN113117076A (en
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林敏�
赵聘
隋坤艳
程燕茹
刘颖颖
夏延致
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Qingdao University
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Abstract

The invention discloses a preparation method of a gel gold nanocluster compound, the compound and application thereof, and belongs to the technical field of functional materials. The stable gel gold nanocluster is prepared by controlling the molecular weight and the concentration of natural polysaccharide and the content of chloroauric acid, has pH response performance, and can be obtained in different aggregation degrees by controlling the pH and the action time. In an open system, the gel gold nanoclusters exist in a dispersed and stable state in a neutral environment, and the photo-thermal conversion performance is in a closed state. However, aggregation occurs when the gel gold nanoclusters are in an acidic environment, and the aggregated gel gold nanoclusters have good photo-thermal conversion performance.

Description

Preparation method of gel gold nanocluster compound, compound and application
Technical Field
The invention belongs to the fields of chemistry and chemical engineering, medical materials and functional materials, and particularly relates to a flexible sodium alginate-gold nanocluster composite gel material with pH response functionality as a tumor CT imaging diagnosis and photothermal treatment reagent. The irradiation with near infrared laser can kill tumor cells with little damage to healthy tissue and organs.
Background
Efficient killing of tumor cells and harmless treatment of healthy tissue and organs have been targets of researchers. It is well known that near infrared light in a biological tissue window has a characteristic of being strong in penetrating ability and not substantially damaging in biological tissue, and thus it has become a hot spot of research to kill tumor cells by irradiating photothermal agents with near infrared light to generate heat. The property of converting light into heat and the property of minimizing damage to human tissues and organs have wide potential application prospects in diagnostic and therapeutic methodologies. Nanoagents for photothermal therapy are of a wide variety and include organic, polymeric, carbon materials, inorganic, and combinations thereof. The most common inorganic nanomaterials among these consist mainly of noble metal materials and copper and oxygen compounds. Taking noble metal gold as an example, gold can be prepared into various shapes, such as rod-shaped, sheet-shaped, star-shaped, cage-shaped and the like, and has good absorption to near infrared light, so that the gold nanocomposite with different shapes is widely tested in terms of photo-thermal performance, however, the preparation process of the gold nanocomposite with different shapes is complex, the preparation condition is harsh, and the metal melting effect appears under the irradiation of long-time near infrared laser, so that the structure is damaged, and the application of the gold nanocomposite as a photo-thermal reagent is limited. In contrast, the spherical gel gold nanocluster prepared by the method has the advantages of stable structure, wide raw material sources, simple preparation method, low condition requirement, high preparation repeatability and large-dose preparation. The monodisperse gel gold nanocluster has particularly poor photo-thermal conversion performance, but the photo-thermal conversion performance is remarkably improved after pH response aggregation.
Disclosure of Invention
The invention aims to provide a method for preparing a gel gold nanocluster compound by using a natural polysaccharide polymer, wherein the gel gold nanocluster compound is a good, stable and intelligent photo-thermal treatment reagent which can be applied to system diagnosis and treatment, and can effectively kill tumor cells under the irradiation of near infrared laser without damaging healthy tissues and organs.
The gel gold nanocluster is prepared by adopting a thermal reduction method, and the gel gold nanoclusters with different performances are prepared by changing the concentration and molecular weight (or viscosity) of the natural polysaccharide polymer solution. The gel gold nanocluster has excellent photo-conversion heat performance after pH response aggregation, and can be used for photo-thermal experiments. In order to increase the stability and the light-conversion heat performance, different pH values or action time are used for controlling the aggregation degree of the gel gold nanoclusters, and by taking potassium phthalate as an example and regulating the pH value and the action time of the potassium phthalate, the gel gold nanocomposite with different aggregation degrees is obtained.
The gold source used in the invention is spherical gel gold nanoclusters of 3-6nm, and the gold source can be prepared in large scale, and has high repeatability and good stability. The adopted raw materials can be purchased directly in commerce, the raw materials are not required to be further processed, and the raw materials are directly and uniformly mixed according to a certain proportion and then are conveyed to a heating table for heating and stirring, so that the experimental operation is simple and convenient, the danger is low, and the repeatability is good. The method can be suitable for preparing gel gold nano-composites aggregated to different degrees, and only pH or action time is required to be controlled.
The water-soluble gel gold nano-composite can be used as a photo-thermal treatment reagent in the pH response of the gel gold nano-clusters with different aggregation degrees, and in an open system, the local temperature of the aggregated gel gold nano-clusters can be quickly raised to more than 50 ℃ under the irradiation of 660nm laser for 8 minutes, so that the condition that tumor cells are killed can be completely met without damaging healthy tissues and organs.
In a preferred embodiment, the method comprises the steps of:
step 1, preparing natural polysaccharide polymer solution;
and step 2, adding chloroauric acid into the natural polysaccharide polymer solution, heating until the solution is boiled, and preferably keeping the boiling for 20-35 min to obtain the gel gold nanocluster compound.
In a preferred embodiment, the natural polysaccharide polymer is a polysaccharide polymer of oxy acid groups, preferably at least one selected from sodium alginate, pectin, agar, xanthan gum, more preferably sodium alginate.
In a further preferred embodiment, the natural polysaccharide polymer has a viscosity of 9 to 430 mPa-s.
In a preferred embodiment, in step 1, the natural polysaccharide polymer solution has a mass concentration of 0.05 to 2.5wt%.
In a further preferred embodiment, in step 1, the mass concentration of the natural polysaccharide polymer solution is 0.25wt% to 2wt%.
In a preferred embodiment, in step 2, the chloroauric acid is present in the natural polysaccharide polymer solution at a mass concentration of
Figure BDA0002369141960000031
In a further preferred embodiment, in step 2, the mass concentration of the chloroauric acid in the natural polysaccharide polymer solution is
Figure BDA0002369141960000032
In a preferred embodiment, in step 2, optionally a reducing agent is also added.
In a further preferred embodiment, the ratio of the amount of chloroauric acid to the amount of reducing agent is 1:5 to 70, preferably 1:15 to 45.
In a still further preferred embodiment, in step 2, the reducing agent is selected from at least one of sodium alginate, small molecule sodium citrate, ascorbic acid, glutathione, cysteine, sodium borohydride.
Specifically, the method comprises the following steps:
adding chloroauric acid (mass fraction) into the dissolved natural polysaccharide polymer (mass fraction: 0.05-2.5 wt.%)The number:
Figure BDA0002369141960000041
) After stirring and mixing uniformly, optionally adding a reducing agent, wherein the reducing agent can be high molecular sodium alginate, small molecular sodium citrate or inorganic sodium borohydride and the like. And (3) moving to a heating table to heat to boiling for a period of time to obtain the gold sol nanoclusters taking the natural polysaccharide polymer as a ligand. Wherein the natural polysaccharide polymer is used for preparing a stabilizer and a reducing agent of the gel gold nanocluster, and then the gold nanoclusters with different aggregation degrees are obtained by treatment with different pH values or time.
The second object of the present invention is to provide a gel gold nanocluster composite obtained by the method according to one of the objects of the present invention.
The gel gold nanocluster compound has pH response performance, and gel gold nanoclusters with different aggregation degrees can be obtained by controlling pH and action time. In an open system, the gel gold nanoclusters exist in a dispersed and stable state in a neutral environment, and the photo-thermal conversion performance is in a closed state. However, aggregation occurs when the gel gold nanoclusters are in an acidic environment, and the aggregated gel gold nanoclusters have good photo-thermal conversion performance. In an open system, gel gold nanoclusters with two different forms are subjected to 2W/cm for 8 minutes at room temperature of 20 DEG C 2 The temperature was raised to-32 and-52℃respectively by 660nm laser irradiation. The gel gold nanocluster composite is an excellent intelligent photo-thermal treatment reagent.
The invention also aims to provide an application of the gel gold nanocluster compound in a photothermal therapeutic agent.
Drawings
Fig. 1-1 shows the ultraviolet-near infrared absorption spectrum of the gel gold nanoclusters obtained in example 1, and fig. 1-2 shows the transmission electron micrographs corresponding to the gel gold nanoclusters obtained in example 1.
Fig. 2-1 shows the ultraviolet-near infrared absorption spectrum of the gel gold nanoclusters obtained in example 2, and fig. 2-2 shows the transmission electron micrographs corresponding to the gel gold nanoclusters obtained in example 2.
Fig. 3-1 shows the ultraviolet-near infrared absorption spectrum of the gel gold nanoclusters obtained in example 3, and fig. 3-2 shows the transmission electron micrographs corresponding to the gel gold nanoclusters obtained in example 3.
Fig. 4-1 shows the ultraviolet-near infrared absorption spectrum of the gel gold nanoclusters obtained in example 4, and fig. 4-1 shows the transmission electron micrographs corresponding to the gel gold nanoclusters obtained in example 4.
Fig. 5-1 shows the ultraviolet-near infrared absorption spectrum of the gel gold nanoclusters obtained in example 5, and fig. 5-2 shows the transmission electron micrographs corresponding to the gel gold nanoclusters obtained in example 5.
Fig. 6-1 shows the ultraviolet-near infrared absorption spectrum of the gel gold nanoclusters obtained in example 6, and fig. 6-2 shows the transmission electron micrographs corresponding to the gel gold nanoclusters obtained in example 6.
Fig. 7-1 shows the ultraviolet-near infrared absorption spectrum of the gel gold nanoclusters obtained in example 7, and fig. 7-2 shows the transmission electron micrographs corresponding to the gel gold nanoclusters obtained in example 7.
Fig. 8-1 shows the ultraviolet-near infrared absorption spectrum of the gel gold nanoclusters obtained in example 8, and fig. 8-2 shows the transmission electron micrographs corresponding to the gel gold nanoclusters obtained in example 8.
Fig. 9-1 shows the ultraviolet-near infrared absorption spectra of the gel gold nanoclusters obtained in example 9 before pH response (peak on the left) and after pH response (peak on the right), and fig. 9-2 shows the transmission electron microscope photograph of the gel gold nanoclusters obtained in example 9 after corresponding to pH response.
Detailed Description
The invention is further illustrated below in conjunction with examples, which are not intended to limit the invention thereto.
Example 1
Preparing sodium alginate solution with volume of 100mL and mass fraction of 2wt% with sodium alginate with viscosity of 430 mPa.s, adding HAuCl 14.8mg after sodium alginate is completely dissolved 4 ·4H 2 And O, after the mixture is uniformly mixed, transferring the mixture to a heating stirring table, and heating the mixture to boil for 30min to prepare the gel gold nanocluster.
Example 2
Preparing sodium alginate solution with volume of 100mL and mass fraction of 1wt% with sodium alginate with viscosity of 430 mPa.s, adding HAuCl 14.8mg after sodium alginate is completely dissolved 4 ·4H 2 And O, after the mixture is uniformly mixed, transferring the mixture to a heating stirring table, and heating the mixture to boil for 30min to prepare the gel gold nanocluster.
Example 3
Preparing sodium alginate solution with volume of 100mL and mass fraction of 0.5wt% with sodium alginate with viscosity of 430 mPa.s, adding 14.8mg of HAuCl after sodium alginate is completely dissolved 4 ·4H 2 And O, after the mixture is uniformly mixed, transferring the mixture to a heating stirring table, and heating the mixture to boil for 30min to prepare the gel gold nanocluster.
Example 4
Preparing sodium alginate solution with volume of 100mL and mass fraction of 0.25wt% with sodium alginate with viscosity of 430 mPa.s, adding 14.8mg of HAuCl after sodium alginate is completely dissolved 4 ·4H 2 And O, after the mixture is uniformly mixed, transferring the mixture to a heating stirring table, and heating the mixture to boil for 30min to prepare the gel gold nanocluster.
Example 5
Preparing sodium alginate solution with volume of 100mL and mass fraction of 2wt% with sodium alginate with viscosity of 9mPa.s, adding HAuCl 14.8mg after sodium alginate is completely dissolved 4 ·4H 2 And O, after the mixture is uniformly mixed, transferring the mixture to a heating stirring table, and heating the mixture to boil for 30min to prepare the gel gold nanocluster.
Example 6
Preparing sodium alginate solution with volume of 100mL and mass fraction of 1wt% with sodium alginate with viscosity of 9mPa.s, adding HAuCl 14.8mg after sodium alginate is completely dissolved 4 ·4H 2 And O, after the mixture is uniformly mixed, transferring the mixture to a heating stirring table, and heating the mixture to boil for 30min to prepare the gel gold nanocluster.
Example 7
Preparing sodium alginate solution with volume of 100mL and mass fraction of 0.5wt% with sodium alginate with viscosity of 9mPa.s, and waiting for seaAfter complete dissolution of sodium alginate, 14.8mg of HAuCl was added to the solution 4 ·4H 2 And O, after the mixture is uniformly mixed, transferring the mixture to a heating stirring table, and heating the mixture to boil for 30min to prepare the gel gold nanocluster.
Example 8
Preparing sodium alginate solution with volume of 100mL and mass fraction of 0.25wt% with sodium alginate with viscosity of 9mPa.s, adding 14.8mg of HAuCl after sodium alginate is completely dissolved 4 ·4H 2 And O, after the mixture is uniformly mixed, transferring the mixture to a heating stirring table, and heating the mixture to boil for 30min to prepare the gel gold nanocluster.
Example 9
Preparing sodium alginate solution with volume of 100mL and mass fraction of 0.25wt% with sodium alginate with viscosity of 9mPa.s, adding 14.8mg of HAuCl after sodium alginate is completely dissolved 4 ·4H 2 And O, after the mixture is uniformly mixed, transferring the mixture to a heating stirring table, and heating the mixture to boil for 30min to prepare the gel gold nanocluster. The prepared gel nano particles are placed in an acidic environment, and the aggregated gel gold nano clusters can be obtained.
Example 10
The procedure of example 9 was repeated except that pectin was used instead of sodium alginate and 1g of small molecular sodium citrate was simultaneously added in step 2 to prepare gel gold nanoclusters. Exhibits the same properties as the gel gold nanoclusters described in example 9, and also has pH responsiveness.
Example 11
The procedure of example 9 was repeated except that sodium alginate was replaced with xanthan gum, and 1g of ascorbic acid was simultaneously added in step 2 to prepare a gel gold nanocluster. Exhibits the same properties as the gel gold nanoclusters described in example 9, and also has pH responsiveness.

Claims (4)

1. A method for preparing a gel gold nanocluster composite by using a natural polysaccharide polymer, comprising the following steps:
step 1, preparing a natural polysaccharide polymer solution, wherein the natural polysaccharide polymer is a polysaccharide polymer with oxo acid groups, the viscosity of the natural polysaccharide polymer is 9 mPa.s-430 mPa.s, and the mass concentration of the natural polysaccharide polymer solution is 0.25-2 wt%;
step 2, adding chloroauric acid into the natural polysaccharide polymer solution, heating until the solution is boiled to obtain a gel gold nanocluster compound, wherein the mass concentration of the chloroauric acid in the natural polysaccharide polymer solution is as follows
Figure FDA0004238646490000011
The natural polysaccharide polymer is selected from sodium alginate.
2. The method according to claim 1, wherein in step 2, the mass concentration of chloroauric acid in the natural polysaccharide polymer solution is
Figure FDA0004238646490000012
3. A gel gold nanocluster compound is prepared by the method of any one of claims 1-2, and has pH response performance, the gel gold nanocluster is in a dispersed and stable state in a neutral environment, the photo-thermal conversion performance is in a closed state, aggregation can occur when the gel gold nanocluster is in an acidic environment, and the aggregated gel gold nanocluster has good photo-thermal conversion performance.
4. Use of the gel gold nanocluster composite of claim 3 in the preparation of a photothermal therapeutic agent.
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