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Preparation method and application of indocyanine green loaded self-assembled multifunctional nano targeting system

A technology of self-assembled nanoparticles and indocyanine green, which is applied in the field of medicine, can solve problems such as single function, high toxicity and side effects, and short half-life, and achieve simple and convenient synthesis process, good biocompatibility, and high targeting Effect

Inactive Publication Date: 2015-12-30
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] In view of the above situation, in order to overcome the defects of the prior art, the purpose of the present invention is to provide a preparation method and application of a self-assembled multifunctional nano-targeting system loaded with indocyanine green, which can effectively solve the problem of existing antitumor drugs. Due to the poor targeting of tumor therapy, large toxic and side effects, short half-life, large dosage, single function and other problems

Method used

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  • Preparation method and application of indocyanine green loaded self-assembled multifunctional nano targeting system

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Effect test

Embodiment 1

[0024] In concrete implementation, the present invention can be realized by the following steps:

[0025] (1) Synthesis of self-assembled nanoparticles (DOX-S-S-HCQ):

[0026] ①Put 54.6mg of 2,2'-dithiodiacetic acid and 1.8ml of thionyl chloride as the connecting arm into a round bottom flask, add 15μl of N,N-dimethylformamide (DMF), stir and reflux at 85°C After 4 hours, the color changed from light yellow to orange; use a rotary evaporator to remove excess thionyl chloride, then add 1ml N,N-dimethylformamide (DMF) to obtain an acid chloride solution;

[0027] ② Dissolve 0.3 mmol of hydroxychloroquine in 0.9 ml of N,N-dimethylformamide (DMF), add 60 μl of triethylamine, add dropwise to the acid chloride solution under stirring in an ice bath, and react in an oil bath at 45°C for 8 hours to obtain acid chloride Hydroxychloroquine solution;

[0028] ③Dissolve 0.3mmol of doxorubicin (DOX) in 1.8ml of N,N-dimethylformamide (DMF), add 60μl of triethylamine, add it dropwise into ...

Embodiment 2

[0036] The present invention can also be realized by the following steps in concrete implementation:

[0037] (1) Synthesis of self-assembled nanoparticles (DOX-S-S-HCQ):

[0038] ①Put 84mg of 3,3'-dithiodipropionic acid and 2.4ml of thionyl chloride in a flask, add 15μl of N,N-dimethylformamide, stir and reflux at 85°C for 4 hours, the color changes from light to light The yellow color becomes orange; use a rotary evaporator to remove excess thionyl chloride, then add 1.5ml N,N-dimethylformamide (DMF) to obtain an acid chloride solution;

[0039]②Dissolve 0.4mmol of hydroxychloroquine in 1.2ml of N,N-dimethylformamide (DMF), add 80μl of triethylamine, add dropwise to the acid chloride solution under stirring in an ice bath, and react in an oil bath at 55°C for 6h to obtain the acid chloride Hydroxychloroquine solution;

[0040] ③Dissolve 0.4mmol of doxorubicin (DOX) in 2.4ml of N,N-dimethylformamide (DMF), add 80μl of triethylamine, add it dropwise to the acid chlorided hyd...

Embodiment 3

[0048] In specific implementation, the present invention can also be realized by the following steps:

[0049] (1) Synthesis of self-assembled nanoparticles (DOX-S-S-HCQ):

[0050] ①Put 105mg of 3,3'-dithiodipropionic acid and 3ml of thionyl chloride in a flask as a connecting arm, add 15μl of dimethylformamide (DMF), stir and reflux at 85°C for 4h, the color changes from light yellow to Turn into orange; use a rotary evaporator to remove excess thionyl chloride, then add 2ml of dimethylformamide (DMF) to obtain an acid chloride solution;

[0051] ② Dissolve 0.5 mmol of hydroxychloroquine in 1.5 ml of formamide, add 100 μl of triethylamine, add dropwise to the acid chloride solution under stirring in an ice bath, and react in an oil bath at 75°C for 4 hours to obtain the acid chloride hydroxychloroquine solution;

[0052] ③Dissolve 0.5mmol of doxorubicin (DOX) in 3ml of formamide, add 100μl of triethylamine, add it dropwise into the acid chlorided hydroxychloroquine solution ...

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Abstract

The invention relates to a preparation method and application of an indocyanine green loaded self-assembled multifunctional nano targeting system. The indocyanine green loaded self-assembled multifunctional nano targeting system can be used for effectively solving the problems of the existing antitumor drugs in tumor therapy that the targeting property is poor, the toxic or side effects are high, the half decay time is short, the dosage of administration is high, the function is single, and the like. Doxorubicin is connected with hydroxychloroquine in a manner of using disulfide bonds as connecting arms so as to form self-assembled nanoparticles, then, indocyanine green is physically adsorbed into the nanoparticles, and then, the nanoparticles are wrapped by phospholipid polyethylene glycol folic acid so as to form the indocyanine green loaded self-assembled multifunctional nano targeting system, wherein each disulfide bond is 3,3'-dithiodipropionic acid or 2,2'-dithio diacetic acid, and the molecular weight of phospholipid polyethylene glycol folic acid is 1-4kDa. The indocyanine green loaded self-assembled multifunctional nano targeting system is simple and convenient in synthesis process, has the advantages of good biocompatibility, high targeting property, reduction sensitivity, hypotoxicity and the like and is an innovation of pharmaceutical preparations for the diagnosis and treatment of tumors.

Description

technical field [0001] The invention relates to medicine, in particular to a preparation method and application of a self-assembled multifunctional nano-targeting system loaded with indocyanine green. Background technique [0002] In recent years, the incidence of malignant tumors has shown an upward trend. According to relevant data, the mortality rate of malignant tumors among Chinese residents has increased by 82.3% compared with the mid-1970s. With socio-economic development and improvement of people's living standards, changes in dietary structure, population aging and urbanization, chronic non-communicable diseases have become the main cause of death. Among them, malignant tumor is one of the main causes of death in the world at present, and has become a large class of diseases that seriously endanger human life and health and restrict social and economic development. [0003] Doxorubicin (DOX) is an anti-tumor antibiotic, which can inhibit the synthesis of RNA and D...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/704A61K47/34A61K49/00A61K41/00A61P35/00A61K31/4706
Inventor 侯琳张振中王用超杨晓敏张银玲袁玉洁张媛媛单晓宁
Owner ZHENGZHOU UNIV
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