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Polyethyleneimine-cyclodextrin-based multifunctional supramolecular gene delivery system and its preparation method

A polyethyleneimine and cyclodextrin technology, which can be used in other methods of inserting foreign genetic materials, recombinant DNA technology, etc., and can solve problems such as off-target and targeted deletion.

Inactive Publication Date: 2019-02-22
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

MRX34 inhibits 24 known liver cancer-related genes to treat liver cancer through intravenous administration, but at the same time, the loss of its targeting leads to the overexpression of exogenous miR-34a in normal cells, resulting in off-target adverse reactions, which also It is an urgent problem to be solved in the current clinical application of carrier-mediated miR-34a therapy

Method used

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  • Polyethyleneimine-cyclodextrin-based multifunctional supramolecular gene delivery system and its preparation method
  • Polyethyleneimine-cyclodextrin-based multifunctional supramolecular gene delivery system and its preparation method
  • Polyethyleneimine-cyclodextrin-based multifunctional supramolecular gene delivery system and its preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0078] Example 1: Take polyethyleneimine-β-cyclodextrin / (adamantane-disulfide bond-polyethylene glycol / adamantane-polyethylene glycol-SP94) as an example.

[0079] 1) Synthesis of adamantane-disulfide bond-polyethylene glycol

[0080] Weigh 2 g of polyethylene glycol monomethyl ether, dissolve it in 30 ml of dimethyl sulfoxide, add 1 g of N,N'-carbonyldiimidazole (CDI), and stir for 3 hours under nitrogen protection in the dark.

[0081] The reaction solution was added to a mixed solution with a volume of 1 liter of diethyl ether: tetrahydrofuran = 4:1 volume ratio, left to stand in an ice bath for 2 hours, and filtered to obtain a white powder.

[0082] Then all the white powder was dissolved in 20 ml of dimethyl sulfoxide; 2.24 g of cystamine dihydrochloride was weighed and dissolved in 10 ml of dimethyl sulfoxide, and 3 ml of triethylamine was added and stirred for 1 hour.

[0083] The white powder solution was slowly added dropwise to the cystamine dihydrochloride solutio...

Embodiment 2

[0102] Example 2: Take polyethyleneimine-α-cyclodextrin / (adamantane-disulfide bond-polyethylene glycol / adamantane-polyethylene glycol-SP94) as an example.

[0103] 1) Synthesis of adamantane-disulfide bond-polyethylene glycol

[0104] Weigh 1 gram of polyethylene glycol monomethyl ether, dissolve it in 30 ml of dimethyl sulfoxide, add 1 gram of N,N'-carbonyldiimidazole, and stir for 2 hours under the protection of nitrogen in the dark. The reaction solution was added to a mixed solution with a volume ratio of 1 liter of diethyl ether: tetrahydrofuran = 2:1, allowed to stand in an ice bath for 1 hour, and filtered to obtain a white powder. Then all the white powder was dissolved in 20 ml of dimethyl sulfoxide, 1 gram of cystamine dihydrochloride was weighed and dissolved in 10 ml of dimethyl sulfoxide, and 1 ml of triethylamine was added, and stirred for 4 hours.

[0105] The white powder solution was slowly added dropwise to the cystamine solution for 2 hours, and the reactio...

Embodiment 3

[0117] Example 3: Take polyethyleneimine-γ-cyclodextrin / (adamantane-disulfide bond-polyethylene glycol / adamantane-polyethylene glycol-RGD) as an example.

[0118] 1) Synthesis of adamantane-disulfide bond-polyethylene glycol

[0119] Weigh 5 g of polyethylene glycol monomethyl ether, dissolve it in 200 ml of dimethyl sulfoxide, add 3 g of N,N'-carbonyldiimidazole, and stir for 4 hours under the protection of nitrogen in the dark. The reaction solution was added to a mixed solution with a volume of 2 liters of diethyl ether: tetrahydrofuran = 10:1 volume ratio, allowed to stand in an ice bath for 4 hours, and filtered to obtain a white powder. Then all the white powder was dissolved in 40 ml of dimethyl sulfoxide, 10 g of cystamine dihydrochloride was weighed and dissolved in 50 ml of dimethyl sulfoxide, and 10 ml of triethylamine was added, and stirred for 2 hours. The white powder solution was slowly added dropwise to the cystamine dihydrochloride solution for 3 hours, and t...

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Abstract

The invention discloses a multifunctional supramolecular gene delivery system based on polyethyleneimine-cyclodextrin and a preparation method thereof. A polyethyleneimine-cyclodextrin polycationic compound serves as a framework, adamantane-disulfide bond-polyethylene glycol having oxidation reduction reactivity and adamantane-polyethylene glycol-targeting peptide having targeting performance serve as modified groups, polyethyleneimine-cyclodextrin is combined with adamantane-disulfide bond-polyethylene glycol and adamantane-polyethylene glycol-targeting peptide through a self-assembling principle, and a subjective body and an objective body act to form a supramolecular gene carrier. The delivery system is multifunctional, has oxidation reduction sensitivity, specificity for targeting liver cancer and excellent gene transfection efficiency, and can carry functional genes to efficiently treat liver malignant tumor.

Description

technical field [0001] The invention relates to a class of non-viral gene transfection vectors and a preparation method thereof, in particular to a polyethylenimine-cyclodextrin-based multifunctional supramolecular gene delivery system and a preparation method thereof. Background technique [0002] Liver cancer is a highly malignant tumor with 554,000 new cases and 521,000 deaths every year. Poor therapeutic effect and poor prognosis of liver cancer have become one of the recognized clinical problems, which may be related to the complex malignant proliferation mechanism of liver cancer, and miRNA expression mutation is an extremely important regulatory mechanism. miRNAs are a class of non-coding RNAs with a length of 20-24 nucleotides that function in post-transcriptional gene regulation. Studies have shown that some key miRNAs inhibit the growth of malignant tumors by regulating oncogene expression and tumor signaling pathways. Abnormal changes in the regulatory pathways o...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/87C08G83/00
CPCC08G83/008C12N15/87
Inventor 梁廷波胡奇达汤谷平王凯李洋孙旭
Owner ZHEJIANG UNIV
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