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Gadolinium-functionalized copper sulfide nanoparticle and preparation method and application thereof

A nanoparticle and copper sulfide technology, applied in the field of nanomedicine, can solve the problems of restricting large-scale production, harsh reaction conditions, and fast clearance rate in the body, and achieve good clinical medical transformation application prospects, improve image contrast, and good photothermal performance effect

Active Publication Date: 2021-12-07
HARBIN MEDICAL UNIVERSITY
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Problems solved by technology

At present, nano-copper sulfide is mainly synthesized by hydrothermal method, co-precipitation method, thermal decomposition method, etc. These synthesis methods have harsh reaction conditions and cumbersome synthesis processes, which greatly limit its large-scale production, thus limiting its wide application in the field of biomedicine. application
Chinese patent CN201410617810 uses ether, 1-(2-methoxy) imidazole hydrochloride and iodohexyl diethyl phosphate and other organic substances to synthesize nano-copper sulfide, which is not friendly to the environment. The reaction process not only requires high temperature conditions but also takes a long time. long
At present, the main T1 contrast agent used clinically is a small molecule based on gadolinium chelate, its r1 relaxation rate is low, about 3.5-3.8mM-1s-1, it has no specificity to tumor tissue, and its clearance rate is fast in vivo and nephrotoxic

Method used

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  • Gadolinium-functionalized copper sulfide nanoparticle and preparation method and application thereof

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preparation example Construction

[0033] A preparation method of gadolinium functionalized copper sulfide nanoparticles, comprising the following steps:

[0034] (1) dissolving disodium edetate in an acidic solution under magnetic stirring at 55° C. to obtain an aqueous solution of disodium edetate, the acidic solution being a hydrochloric acid solution with a pH value of 5, and the The molar concentration of disodium edetate aqueous solution is 11mmol / L;

[0035] (2) Add gadolinium chloride hexahydrate to the disodium edetate aqueous solution of step (1) under magnetic stirring, carry out chelation reaction, obtain Gd 3+ In the chelate solution, the molar ratio of gadolinium chloride hexahydrate to disodium edetate is 0.18-0.45:1, and the time for the chelation reaction is preferably 30 minutes.

[0036] (3) Bovine serum albumin, polyethylene glycol and copper chloride dihydrate are dissolved in the Gd of step (2) under magnetic stirring 3+ Chelate solution, obtain mixed solution, bovine serum albumin, polyet...

Embodiment 1

[0044] (1) Weigh 32.8 mg of disodium edetate and add it to 8 ml of solvent, and fully stir and dissolve it under the condition of 55°C with a magnetic stirrer;

[0045] (2) Weigh 5.9 mg of gadolinium chloride hexahydrate and stir for 30 min under magnetic stirring at room temperature to obtain a chelated solution.

[0046] (3) Weigh 10 mg of bovine serum albumin, 10 mg of polyethylene glycol, and 23.9 mg of copper chloride dihydrate, add the above-mentioned chelated solution under magnetic stirring at room temperature, and stir for 5 minutes to obtain a light blue mixed solution.

[0047] (4) Add 2ml (168.1mg) sodium sulfide solution to the above mixed solution under normal temperature conditions in a magnetic stirrer, the volume ratio of sodium sulfide nonahydrate solution and mixed solution is 1:4, stir for 5 minutes, the color of the reaction solution gradually turns black Green, the nanoparticle nuclear reaction solution is obtained. Continue to stir the nanoparticle nucl...

Embodiment 2

[0049] (1) Weigh 32.8 mg of disodium edetate and add it into 8 ml of solvent, and fully stir and dissolve in a magnetic stirrer at 55°C.

[0050] (2) Weigh 10.4 mg of gadolinium chloride hexahydrate and stir for 30 minutes under magnetic stirring at room temperature to obtain a chelated solution.

[0051] (3) Weigh 10 mg of bovine serum albumin, 10 mg of polyethylene glycol, and 23.9 mg of copper chloride dihydrate, add the above-mentioned chelated solution under magnetic stirring at room temperature, and stir for 5 minutes to obtain a light blue mixed solution.

[0052] (4) Add 2ml (168.1mg) sodium sulfide solution to the above mixed solution under normal temperature conditions in a magnetic stirrer, the volume ratio of sodium sulfide nonahydrate solution and mixed solution is 1:4, stir for 5 minutes, the color of the reaction solution gradually turns black Green, the nanoparticle nuclear reaction solution is obtained. The nanoparticle nuclear reaction solution was stirred f...

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Abstract

The invention provides a gadolinium-functionalized copper sulfide nanoparticle and a preparation method and application thereof. The gadolinium-functionalized copper sulfide nanoparticle comprises nano copper sulfide, wherein the nano copper sulfide serves as a core, and the surface is wrapped with Gd < 3 + > chelate, bovine serum albumin and polyethylene glycol. The relaxation rate of the copper sulfide nanoparticle is 5.35-6.69 mM <-1 > S <-1 >, the particle size is 10-30 nm, the copper sulfide nanoparticle is dispersed in a phosphate buffer solution to prepare a dispersion liquid, and when a photothermal effect is tested under the condition that the power density of a 808 nm laser is 1.0 Wcm <-2 > and the dispersion liquid is irradiated for 240 s, the temperature is rapidly increased to 55 DEG C from 25 DEG C. The nanoparticle disclosed by the invention has a mild preparation condition, a high yield, a high r1 relaxation rate and good photo-thermal performance, and can be used as a photo-thermal sensitive agent for photo-thermal therapy and a magnetic resonance imaging T1 contrast agent at the same time.

Description

technical field [0001] The invention relates to the technical field of nanomedicine, in particular to a gadolinium-functionalized copper sulfide nanoparticle and a preparation method and application thereof. Background technique [0002] In recent years, visualization therapy, as an auxiliary means of precision medicine, has received widespread attention in anti-tumor therapy. Scientific researchers have found that nano-copper sulfide has strong near-infrared absorption capacity. Compared with traditional gold nanomaterials, its near-infrared absorption peak does not change with changes in size and shape, and has good photothermal stability. It has the characteristics of low cost and low in vivo toxicity, and can be used for photothermal therapy of tumors. At present, nano-copper sulfide is mainly synthesized by hydrothermal method, co-precipitation method, thermal decomposition method, etc. These synthesis methods have harsh reaction conditions and cumbersome synthesis pro...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K9/51A61K47/42A61K47/10A61K49/14A61K49/12A61K49/18
CPCA61K41/0052A61K9/5169A61K9/5146A61K49/143A61K49/126A61K49/1881
Inventor 孙夕林王凯程立欣郑利敏吴丽娜杨洁吴泳仪阿荣张鑫峰乔文菊
Owner HARBIN MEDICAL UNIVERSITY
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