CN111558039A - Method for synthesizing LPS @ CuS Gd photo-immunizing agent - Google Patents
Method for synthesizing LPS @ CuS Gd photo-immunizing agent Download PDFInfo
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Abstract
The invention relates to an LPS @ CuS and Gd photo-immunizing agent successfully prepared by normal-temperature biomimetic synthesis. Comprises (1) preparing CuCl with the concentration of 0.001M2Aqueous solution, 0.0025M GdCl3An aqueous solution. (2) LPS @ CuS and Gd nanoparticles are biomimetically synthesized at normal temperature. The LPS can activate the whole body immune system by utilizing the strong immune activation function, recruit DC cells and cause immune response; gd (Gd)The element-guided MRI imaging visual guidance realizes the light-operated release of tumor antigens, further enhances the ICD effect, induces the organism to generate the immunological memory function and achieves the aim of efficiently and thoroughly treating tumors.
Description
Technical Field
The invention relates to the technical field of photo-immune preparations, in particular to a method for synthesizing an LPS @ CuS/Gd photo-immune agent through normal-temperature biomimetic synthesis.
Background
Recently, tumor immunotherapy has become an important breakthrough and development direction for tumor therapy. Different from the traditional treatment mode, the tumor immunotherapy mainly achieves the aim of treating tumors by activating or improving the immunologic function of a human body, and has small side effect on the human body; meanwhile, immunotherapy has a long-term anti-tumor immune function and can specifically identify tumor cells, so that the metastasis and recurrence of tumors are effectively inhibited. LPS is a compound of lipid and polysaccharide, is a specific chemical component in the outer wall layer of gram-negative bacteria, and has molecular weight of more than 10000. It consists of core polysaccharide, O-polysaccharide side chains, and lipid A. It is a natural ligand for TOLL-like receptor 4(TLR4) and induces DC maturation and a strong TH 1-type immune response. It is therefore intended herein to be used as an immunostimulant to effect immunotherapy.
The photothermal therapy (PTT) is a novel tumor therapy method, under the irradiation of external near infrared light, a photothermal agent at a tumor part absorbs the near infrared light and converts the near infrared light into heat, so that the temperature of the tumor part is rapidly increased to more than 48 ℃, and cancer cells can be killed within a few minutes. The photothermal therapy process has less side effect, low systemic toxicity, no damage to normal tissue and great clinical application potential. If the photothermal therapy and the tumor immunotherapy are combined, the tumor therapy effect is greatly enhanced, and the tumor therapy is more thorough.
The prepared medicine has the following advantages: 1) LPS can activate the whole body immune system by utilizing the strong immune activation function, recruit DC cells and cause immune response; 2) the Gd element-guided MRI imaging visual guidance realizes the light-operated release of tumor antigens, further enhances the ICD effect, induces the organism to generate the immunological memory function, and achieves the aim of efficiently and thoroughly treating tumors.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides an LPS @ CuS and Gd photo-immunizing agent successfully prepared by normal-temperature biomimetic synthesis.
The invention relates to a method for synthesizing an LPS @ CuS Gd photo-immunizing agent; the method comprises the following steps: the method comprises the following steps:
1) weighing copper chloride dihydrate, adding ultrapure water, and ultrasonically dissolving to obtain CuCl with concentration of 0.001-0.004M2An aqueous solution;
2) weighing gadolinium chloride hexahydrate, adding 10mL of ultrapure water, and ultrasonically dissolving to obtain GdCl with concentration of 0.0025-0.01M3An aqueous solution;
3) the method for synthesizing the LPS @ CuS/Gd nano-particles by biomimetic mineralization comprises the following steps:
(1) accurately weighing 0.25-1mg of lipopolysaccharide, adding into a 5mL transparent bottle, adding 5mL of ultrapure water, and ultrasonically dissolving until the powder is fully dissolved to obtain an LPS aqueous solution with the concentration of 0.5-2 mg/mL;
(2) placing 1ml LPS solution single-mouth bottle on 37 deg.C water bath magnetic stirrer, and dripping 5ml CuCl prepared above with disposable dropper under stirring2And 1ml GdCl3Continuously stirring the solution for three minutes after the dropwise addition;
(3) preparing 0.01M NaOH solution, adding 0.5mL of NaOH solution into the reaction system, and adjusting the pH value of the solution to 10;
(4) preparing sodium sulfide nonahydrate solution with the concentration of 0.01-0.03 mmol/mL), and adding 0.04mL into the reaction system;
stirring at 37 deg.C for 3 hr, centrifuging at 10000 rpm, collecting precipitate, repeatedly washing with deionized water for 3 times, and storing at 4 deg.C
The invention has the advantages that: 1) LPS can activate the whole body immune system by utilizing the strong immune activation function, recruit DC cells and cause immune response; 2) the Gd element-guided MRI imaging visual guidance realizes the light-operated release of tumor antigens, further enhances the ICD effect, induces the organism to generate the immunological memory function, and achieves the aim of efficiently and thoroughly treating tumors.
Detailed Description
The present invention will be further described below.
Example 1:
the method for synthesizing the LPS @ CuS Gd photo-immunizing agent comprises the following specific steps:
1) 8.5mg of copper chloride dihydrate was weighed, and dissolved by ultrasonic after adding 50mL of ultrapure water to obtain 0.001M CuCl2An aqueous solution.
2) 9.3mg of gadolinium chloride hexahydrate is weighed, 10mL of ultrapure water is added, and ultrasonic dissolution is carried out to obtain GdCl with the concentration of 0.0025M3An aqueous solution.
3) The method for synthesizing the LPS @ CuS/Gd nano-particles by biomimetic mineralization comprises the following steps:
a) accurately weighing 0.25mg of Lipopolysaccharide (LPS) into a 5mL transparent bottle, adding 5mL of ultrapure water, and ultrasonically dissolving until the powder is fully dissolved to obtain an LPS aqueous solution with the concentration of 0.5 mg/mL.
b) Placing 1ml LPS solution single-mouth bottle on 37 deg.C water bath magnetic stirrer, and dripping 5ml CuCl prepared above with disposable dropper under stirring2And 1ml GdCl3The solution was stirred for three minutes after the addition.
c) 0.01M NaOH solution (4mg,10mL) was prepared, and 0.5mL of the solution was added to the above reaction system to adjust the pH of the solution to 10.
d) Sodium sulfide nonahydrate (Na) with concentration of 0.01mmol/mL is prepared2S·9H2O) solution (24.2mg,10mL), and 0.04mL was added to the reaction system.
e) Stirring at 37 deg.C for 3 hr, taking out reaction solution, centrifuging at 10000 rpm, collecting precipitate, repeatedly adding deionized water, cleaning for 3 times, and storing at 4 deg.C.
Example 2:
the method for synthesizing the LPS @ CuS Gd photo-immunizing agent comprises the following specific steps:
1) 25.5mg of copper chloride dihydrate was weighed, and dissolved by ultrasonic after adding 50mL of ultrapure water to obtain 0.003M CuCl2An aqueous solution.
2) 27.9mg of gadolinium chloride hexahydrate was weighed, and added to 10mL of ultrapure water to be ultrasonically dissolved, thereby obtaining GdCl having a concentration of 0.0075M3An aqueous solution.
3) The method for synthesizing the LPS @ CuS/Gd nano-particles by biomimetic mineralization comprises the following steps:
a) accurately weighing 0.75mg of Lipopolysaccharide (LPS) into a 5mL transparent bottle, adding 5mL of ultrapure water, and ultrasonically dissolving until the powder is fully dissolved to obtain an LPS aqueous solution with the concentration of 1.5 mg/mL.
b) Placing 1ml LPS solution single-mouth bottle on 37 deg.C water bath magnetic stirrer, and dripping 5ml CuCl prepared above with disposable dropper under stirring2And 1ml GdCl3The solution was stirred for three minutes after the addition.
c) 0.01M NaOH solution (4mg,10mL) was prepared, and 0.5mL of the solution was added to the above reaction system to adjust the pH of the solution to 10.
d) Sodium sulfide nonahydrate (Na) with concentration of 0.03mmol/mL is prepared2S·9H2O) and 0.04mL of the solution was added to the reaction system.
e) Stirring at 37 deg.C for 3 hr, taking out reaction solution, centrifuging at 10000 rpm, collecting precipitate, repeatedly adding deionized water, cleaning for 3 times, and storing at 4 deg.C.
Example 3:
the method for synthesizing the LPS @ CuS Gd photo-immunizing agent comprises the following specific steps:
1) 34mg of copper chloride dihydrate was weighed, and 50mL of ultrapure water was added thereto and dissolved by ultrasonic waves to obtain a 0.004M aqueous solution of CuCl 2.
2) 37.2mg of gadolinium chloride hexahydrate was weighed, and dissolved by ultrasonic waves after adding 10mL of ultrapure water to obtain a 0.01M GdCl3 aqueous solution.
3) The method for synthesizing the LPS @ CuS/Gd nano-particles by biomimetic mineralization comprises the following steps:
a) accurately weighing 1mg of Lipopolysaccharide (LPS) and adding into a 5mL transparent bottle, adding 5mL of ultrapure water, and ultrasonically dissolving until the powder is fully dissolved to obtain an LPS aqueous solution with the concentration of 2 mg/mL.
b) A single-necked flask of 1ml of LPS solution was placed on a magnetic stirrer in a water bath at 37 ℃ and then, while stirring, 5ml of CuCl2 and 1ml of GdCl3 solution prepared as described above were added dropwise with a disposable dropper, and stirring was continued for three minutes after the addition.
c) 0.01M NaOH solution (4mg,10mL) was prepared, and 0.5mL of the solution was added to the above reaction system to adjust the pH of the solution to 10.
d) Sodium sulfide nonahydrate (Na) with concentration of 0.04mmol/mL is prepared2S·9H2O) and 0.04mL of the solution was added to the reaction system.
e) Stirring at 37 deg.C for 3 hr, taking out reaction solution, centrifuging at 10000 rpm, collecting precipitate, repeatedly adding deionized water, cleaning for 3 times, and storing at 4 deg.C.
Claims (1)
- The method for synthesizing the LPS @ CuS Gd photo-immunizing agent is characterized by comprising the following steps of:1) weighing copper chloride dihydrate, adding ultrapure water, and ultrasonically dissolving to obtain CuCl with concentration of 0.001-0.004M2An aqueous solution;2) weighing gadolinium chloride hexahydrate, adding 10mL of ultrapure water, and ultrasonically dissolving to obtain GdCl with concentration of 0.0025-0.01M3An aqueous solution;3) the method for synthesizing the LPS @ CuS/Gd nano-particles by biomimetic mineralization comprises the following steps:(1) accurately weighing 0.25-1mg of lipopolysaccharide, adding into a 5mL transparent bottle, adding 5mL of ultrapure water, and ultrasonically dissolving until the powder is fully dissolved to obtain an LPS aqueous solution with the concentration of 0.5-2 mg/mL;(2) placing 1ml LPS solution single-mouth bottle on 37 deg.C water bath magnetic stirrer, and dripping 5ml CuCl prepared above with disposable dropper under stirring2And 1ml GdCl3Continuously stirring the solution for three minutes after the dropwise addition;(3) preparing 0.01M NaOH solution, adding 0.5mL of NaOH solution into the reaction system, and adjusting the pH value of the solution to 10;(4) preparing sodium sulfide nonahydrate solution with the concentration of 0.01-0.03mmol/mL, and adding 0.04mL into a reaction system;(5) stirring at 37 deg.C for 3 hr, taking out reaction solution, centrifuging at 10000 rpm, collecting precipitate, repeatedly adding deionized water, cleaning for 3 times, and storing at 4 deg.C.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108495931A (en) * | 2015-11-11 | 2018-09-04 | 朱正崙 | A method of changing macrophage differentiation and is immunized |
| CN110179837A (en) * | 2019-05-08 | 2019-08-30 | 天津大学 | The synthetic method of the visualization guidance tumour combined immunization treatment nanometer formulation of Gd:CuS mineralising influenza virus |
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- 2020-03-20 CN CN202010203224.8A patent/CN111558039A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108495931A (en) * | 2015-11-11 | 2018-09-04 | 朱正崙 | A method of changing macrophage differentiation and is immunized |
| CN110179837A (en) * | 2019-05-08 | 2019-08-30 | 天津大学 | The synthetic method of the visualization guidance tumour combined immunization treatment nanometer formulation of Gd:CuS mineralising influenza virus |
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