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Plasmid entrapped cationic liposome compound for treating malignant tumors

A technology for cationic liposomes and malignant tumors, applied in the field of cationic liposome complexes and long-circulating cationic liposomes, which can solve the problems of damage, dose dependence, non-specific normal cells, etc.

Pending Publication Date: 2021-04-27
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the above solutions still have dose-dependent non-specific or damage to normal cells

Method used

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  • Plasmid entrapped cationic liposome compound for treating malignant tumors
  • Plasmid entrapped cationic liposome compound for treating malignant tumors
  • Plasmid entrapped cationic liposome compound for treating malignant tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] 960 μg of plasmid DNA and 1.4 mg of chitosan were mixed in 2 mL of HEPES buffer (pH=7.4), vortexed for a few seconds and left to stand for more than 15 minutes to obtain a complex of plasmid DNA and chitosan. Precisely weigh the prescription amount 6.0mg DOTAP, 6.4mg DOPE, 6.7mg HSPC, 4.8mg Chol, 3.9mg DSPE-PEG 2000 In a 100mL eggplant-shaped bottle, add a mixed organic solvent (8mL chloroform, 2mL methanol), and sonicate in a water bath for 1min to fully dissolve it. At 40° C. and 45 rpm, the organic solvent was evaporated under reduced pressure to obtain a transparent and uniform liposome film. Blow off residual chloroform with high-pressure nitrogen, and place in a refrigerator at 4°C overnight. Then add the 2mL HEPES buffer containing the complex of plasmid DNA and chitosan prepared above, shake fully, and completely dissolve the lipid on the wall. Incubate for one hour with stirring in a 60°C water bath. The liposomes were sonicated (100W, 10min, working 1s, int...

Embodiment 2

[0035] 960 μg of plasmid DNA and 1.4 mg of chitosan were mixed in 3 mL of HEPES buffer (pH=7.4), vortexed for a few seconds and left to stand for more than 15 minutes to obtain a complex of plasmid DNA and chitosan. Accurately weigh the prescription amount 6.0mg DOTAP, 6.4mg DOPE, 9.1mg EPC, 4.5mg Chol, 3.9mg DOPE-PEG 2000 -cRGD was added to a 100mL eggplant-shaped bottle, mixed with organic solvents (8mL chloroform, 2mL methanol), and ultrasonically dissolved in a water bath for 2min to fully dissolve it. At 42° C. and 45 rpm, the organic solvent was evaporated under reduced pressure to obtain a transparent and uniform liposome film. Blow off residual chloroform with high-pressure nitrogen, and place in a refrigerator at 4°C overnight. Afterwards, 3 mL of the HEPES buffer containing the complex of plasmid DNA and chitosan prepared above was added and shaken sufficiently to completely dissolve the lipids on the wall. Incubate for one hour with stirring in a 42°C water bath. ...

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Abstract

The invention relates to a plasmid DNA entrapped cationic liposome compound. The plasmid DNA entrapped cationic liposome compound consists of a cationic liposome, and chitosan and plasmid DNA wrapped by the cationic liposome, wherein the cationic liposome consists of cationic phospholipid DOTAP, neutral phospholipid HSPC or EPC, auxiliary phospholipid DOPE, cholesterol Chol, and functional phospholipid DSPE-PEG2000-X or DOPE-PEG2000-X; the plasmid DNA is a recombinant photosensitive transcription factor expression gene and diphtheria toxin A fragment (DT-A) transcription unit; the plasmid DNA for light-operated expression of diphtheria toxin is firstly compressed by chitosan, and then entrapped into the cationic liposome; and various groups can be modified on the surface of the cationic liposome, so that a drug delivery system has a certain targeting effect, and the treatment effect on malignant tumors is good.

Description

technical field [0001] The present invention relates to a cationic liposome complex carrying a plasmid for the treatment of malignant tumors, in particular to a long-circulating (targeting) cationic liposome carrying a light-controlled expression of diphtheria toxin plasmid DNA, which can be used for The treatment of malignant tumors belongs to the technical field of biomedicine. Background technique [0002] As one of the important factors causing death worldwide, malignant tumor has become the second largest disease affecting human health. Diphtheria toxin (DT) is a toxin secreted by Corynebacterium diphtheriae. Diphtheria toxin A fragment (DTA) is extremely toxic and can catalyze the ADP ribose group on NAD+ to elongation factor-2 (Elongation factor-2). 2, EF-2) transfer, thereby inhibiting the protein synthesis of cells. Because traditional treatment methods such as chemotherapy are prone to defects such as drug resistance, DT has emerged in the study of tumor diseases...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K38/16A61K48/00A61K47/60A61K41/00A61P35/00B82Y5/00B82Y30/00B82Y20/00B82Y40/00
CPCA61K41/0042A61K47/6911A61K47/60A61P35/00A61K48/005A61K48/0041A61K38/164B82Y5/00B82Y30/00B82Y20/00B82Y40/00
Inventor 高峰陈显军杨弋赵玉政贺牧野陈彦佐徐嘉俊扎娜·艾特·巴希尔侯昕宇寿晨汀王研蔡晓然程驿张苗王杰丁芷瑄汪晓蕾孙余吉王艳兵孙锐吕英妮孙玲娜殷语边依真陈泽坤张满湛
Owner EAST CHINA UNIV OF SCI & TECH
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