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Copolymer nucleic acid carrier containing metal-coordinated pyridine derivative ligand, preparation method and application

A metal coordination and nucleic acid carrier technology, which is applied in the field of preparation of copolymer nucleic acid carriers, can solve the problems of low charge density, high cytotoxicity, and high positive charge density, and achieve low cytotoxicity, high endocytosis efficiency, and high transfection efficiency effect

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

AI Technical Summary

Problems solved by technology

[0003] The purpose of the present invention is to provide a low charge density, multifunctional copolymer containing metal-coordinated pyridine derivative ligands in view of the high positive charge density of current polycationic nucleic acid carriers and the high cytotoxicity of in vivo applications. Nucleic acid carrier preparation method and application

Method used

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  • Copolymer nucleic acid carrier containing metal-coordinated pyridine derivative ligand, preparation method and application
  • Copolymer nucleic acid carrier containing metal-coordinated pyridine derivative ligand, preparation method and application
  • Copolymer nucleic acid carrier containing metal-coordinated pyridine derivative ligand, preparation method and application

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Embodiment 1

[0019] A copolymer nucleic acid carrier material containing metal-coordinated pyridine derivative ligands, composed of a coordination unit lutidine amine group and a stimulus-response unit containing a disulfide bond monomer N,N'-bis(acryloyl)cyst The functional monomer containing pyridine derivative ligand composed of amine (CBA) is synthesized by controlled free radical polymerization with the hydrophilic monomer hydroxyethyl methacrylate (HEMA) and the hydrophobic monomer n-butyl methacrylate , the coordination metal is zinc (Zn) ion, the copolymer nucleic acid carrier material structural formula of the pyridine derivative ligand of zinc coordination is shown as follows:

[0020]

[0021] The preparation method of the copolymer nucleic acid carrier material containing the metal-coordinated pyridine derivative ligand shown in the above structural formula comprises the following steps:

[0022] 1) Preparation of metal ligand functional monomer DPASS

[0023] Dissolve 16mm...

Embodiment 2

[0028] A copolymer nucleic acid carrier material containing a metal-coordinated pyridine derivative ligand, a functional monomer containing a pyridine derivative ligand composed of a coordination metal, a coordination unit, and a stimuli-response unit, a hydrophilic monomer and a hydrophobic Composed of monomers, the coordination metal is magnesium (Mg), the coordination unit is a lutidine amine group, and the stimulus response unit is a disulfide bond-containing monomer bis(2-propylene)ethoxydisulfide (DSDA ); the hydrophilic monomer is hydroxyethyl methacrylate; the hydrophobic monomer is isopropyl acrylamide.

[0029] A method for preparing the copolymer carrier Mg-HDN containing metal-coordinated pyridine derivative ligands, comprising the steps of:

[0030] 1) Preparation of metal ligand functional monomer DDAD

[0031]Dissolve 20mmol of 1,4-p-dichlorobenzyl (Dx) in 20mL of dichloromethane, add 10mmol of lutidine amine (DPA) and 45mmol of anhydrous potassium carbonate, s...

Embodiment 3

[0035] The application of the prepared copolymer containing metal-coordinated pyridine derivative ligands is used as a nucleic acid carrier to deliver deoxyribonucleic acid (DNA) to cells. The method is as follows: the metal-coordinated pyridine derivative prepared in Example 1 The ligand copolymer Zn-HDB was mixed with DNA in equal volumes, and allowed to stand at room temperature for 15 minutes to prepare DNA complexes with mass ratios of 20, 40, and 60:1; the prepared complexes were used to transfect different cells Department, the method is as follows:

[0036] Cell Transfection Steps

[0037] 1) Preparation of DNA complex:

[0038] The DNA used is the green fluorescent protein plasmid pCMV-GFP and the luciferase plasmid pCMV-GLuc. Dissolve the copolymer Zn-HDB containing metal-coordinating pyridine derivative ligands prepared in Example 1 and DNA in acetate buffer at pH 5.2, mix equal volumes, and let stand at room temperature for 15 minutes to obtain a DNA complex Nan...

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Abstract

A copolymer nucleic acid carrier containing a metal coordination pyridine derivative ligand, a preparation method and application thereof are disclosed. The carrier is composed of a ligand functionalmonomer composed of a coordinated metal, a coordination unit and a stimulus-response unit, a hydrophilic functional monomer, and a hydrophobic functional monomer. The copolymer non-viral carrier material containing the metal coordination pyridine derivative ligand that is prepared by a controllable polymerization mode has strong DNA binding ability and interaction with a cell membrane, and the obtained DNA complex has high endocytosis efficiency. After the complex enters cells, due to the stimulus-response, the metal ion ligand unit is disconnected from the copolymer backbone, and the DNA is released and expressed, thus exhibiting high transfection efficiency. Meanwhile, due to the small amount of cations in the copolymer system, the positive charge density of the copolymer and the nucleicacid complex is low, and cytotoxicity of the complex is low. Therefore, the metal-containing coordination pyridine derivative ligand copolymer is a novel low-charge-density non-viral nucleic acid carrier material with good clinical potential.

Description

technical field [0001] The invention belongs to the field of gene therapy and new materials, and specifically relates to a preparation method and application of a copolymer nucleic acid carrier containing metal-coordinated pyridine derivative ligands. Background technique [0002] Gene therapy achieves the purpose of treating diseases by delivering therapeutic functional nucleic acid molecules to specific cells of patients, and it can provide many major diseases that cannot be cured in humans at present, such as cancer, genetic diseases (such as hemophilia), infectious diseases (such as , AIDS and rheumatoid diseases, etc.) and cardiovascular diseases have brought hope. The key to the successful realization of gene therapy is how to construct a safe and efficient nucleic acid delivery system to deliver the therapeutic gene to the treatment site and efficiently transfect it. At present, viral vectors are mainly used clinically. Although viral vectors show very impressive tra...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08F220/18C08F220/20C08F230/04C08F220/54C12N15/87
CPCC08F220/18C08F220/54C12N15/87C08F220/1804C08F220/20C08F230/04
Inventor 郭天瑛刘帅贾惠婷潘建萍
Owner NANKAI UNIV
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