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Application of artemisinin and derivative thereof to preparation of sensitizer for thermodynamic therapy

A thermodynamic and derivative technology, applied in the field of functional materials and drugs, to achieve the effects of being beneficial to clinical use and promotion, high human safety, and ingenious overall design

Active Publication Date: 2020-12-15
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The use of artesunate and indocyanine green in liposomes to prepare nanomaterials for photothermal therapy and thermodynamic therapy of tumors has not been reported yet.

Method used

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  • Application of artemisinin and derivative thereof to preparation of sensitizer for thermodynamic therapy
  • Application of artemisinin and derivative thereof to preparation of sensitizer for thermodynamic therapy
  • Application of artemisinin and derivative thereof to preparation of sensitizer for thermodynamic therapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1 Artemisinin derivatives as thermodynamic therapy sensitizers

[0027] 2',7'-dichlorofluorescein diacetate (abbreviated as DCFH-DA) hydrolysis product 2',7'-dichlorofluorescein diacetic acid (referred to as DCFH) is used as a probe for active oxygen, and the excitation wavelength of the probe is 488nm, the emission wavelength detection range is 500-600nm. The preparation of the hydrolyzed aqueous solution of DCFH-DA refers to existing papers (" J. Immunol. Methods》 1993, 159 (1-2), 131-138 carried out). By observing the fluorescence of DCFH (at around 524nm) in the solution containing the sample to be tested with the laser irradiation time, the ability of the sample to generate ROS thermally was determined. The stronger the fluorescence intensity generated by DCFH, the stronger the thermally sensitive ROS generation ability.

[0028] Taking artesunate (ARS) as an example for determination, the specific determination method is to weigh an appropriate amount...

Embodiment 2

[0031]Through literature research and experiments, it is found that when the concentration of indocyanine green reaches 100 μM, the aqueous solution in which it is located can be heated to 50 ° C, which can meet the requirements of artesunate to generate active oxygen by heating. The ratio of green found that the ratio of artesunate to indocyanine green will show different properties within a certain range, such as figure 1 As shown, artesunate: indocyanine green = 1:1 and artesunate: indocyanine green = 2:1 have the strongest ability to generate active oxygen and have the same intensity, so indocyanine green is selected as the drug for laser irradiation A heat source was generated, and artesunate: indocyanine green = 1:1 was used as the optimal drug ratio form.

Embodiment 3

[0032] Example 3 Liposome nano-drug loaded with indocyanine green and artesunate

[0033] Weigh dipalmitoylphosphatidylcholine, distearoylphosphatidylethanolamine-polyethylene glycol 2000, cholesterol hemisuccinate, artesunate and indole at a molar ratio of 12:1.5:9:3:13 Cyanine green, add chloroform (10 mL) and methanol (10 mL), dissolve it in the mixed solvent, and then sonicate for 5 min. Then the solution was dried by rotary evaporation, and further deionized (DI) water was used to form liposome suspension. The liposome suspension was then pulverized by an ultrasonic cell disruptor at 10°C for 10 minutes, and dialyzed against deionized water (membrane molecular weight cut-off 10,000) at 25°C for 48 hours to remove free indocyanine green and artemisia annua succinate to obtain ICG-ARS@NPs.

[0034] Electron microscope analysis showed that the obtained liposome nanocomplex was relatively uniform spherical or near-spherical vesicles with a particle diameter of about 150 nm....

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Abstract

The invention provides new application of artemisinin and a derivative thereof, namely that the artemisinin or the derivative thereof is directly used as a sensitizer for thermodynamic therapy, and isused for thermodynamic therapy of tumors; or a liposome nano-composite prepared from the artemisinin and the derivative thereof and indocyanine green is used as a sensitizer for the thermodynamic therapy, and is used for thermodynamic therapy and / or photothermal therapy of the tumors. when being used for thermodynamic therapy of the tumors, the artemisinin or the derivative thereof and the liposome nano-composite not only show excellent tumor targeting performance, but also have extremely high synergistic photothermal therapy and thermodynamic therapy anti-tumor activity, and have remarkableadvantages as an anti-cancer drug.

Description

technical field [0001] The invention belongs to the field of functional materials and medicines, and specifically relates to the application of artemisinin derivatives, artemisinin derivatives and indocyanine green liposome nanomaterials in antitumor. Background technique [0002] Photodynamic therapy (PDT) is a therapeutic approach against cancer that utilizes light to excite photosensitizers followed by photochemical reactions in the presence of oxygen to generate reactive oxygen species (ROS) that induce cancer cells and tissue damage. PDT has been widely developed due to its advantages of minimal invasiveness and non-drug resistance. Recently, a new approach, thermodynamic therapy (TDT), has emerged. It uses heat as an energy source to activate sensitizers, which then generate ROS or other free radicals for cancer treatment. Heat can be provided in more ways than light, such as chemical reactions, light, ultrasound, radiation, and microwaves. Therefore, TDT is a novel...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K31/366A61K31/357A61K9/127A61P35/00A61K49/00
CPCA61K41/0052A61K41/0057A61K31/366A61K31/357A61K9/127A61P35/00A61K49/0034A61K2300/00A61K31/404
Inventor 黄剑东赵鹏辉柯美荣郑碧远
Owner FUZHOU UNIV
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