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A nucleic acid delivery carrier and its preparation method and application

A delivery carrier and nucleic acid technology, which is applied in the field of nanomaterials, can solve the problems of oligopolyethyleneimine that does not have gene delivery, achieve high nucleic acid delivery efficiency, improve nucleic acid compression ability, and simple methods

Active Publication Date: 2020-07-31
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Unfortunately, oligopolyethylenimines do not have gene delivery capabilities

Method used

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  • A nucleic acid delivery carrier and its preparation method and application
  • A nucleic acid delivery carrier and its preparation method and application
  • A nucleic acid delivery carrier and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] In this embodiment, the nucleic acid delivery carrier is a nanometer self-assembly of amphiphilic fluorinated material, and the amphiphilic fluorinated material is perfluorooctyl substituted oligomer polyethyleneimine.

[0059] The nucleic acid delivery vector is prepared by the following method, which specifically includes the following steps:

[0060] (1) Synthesis of amphiphilic fluorinated materials

[0061] Weigh 418.2mg of oligopolyethyleneimine (Mn=600Da, Sigma) and dissolve it in 35mL of anhydrous dichloromethane, stir thoroughly to dissolve it completely, and then place it in an ice-water mixing bath; Take 169.1 μL of anhydrous triethylamine, add it to the above-mentioned polyethyleneimine reaction solution, and continue to stir for 30 min; (120.3 μL) was added dropwise to the above reaction solution for a total of 2 hours. Stirring was continued for 3 h at room temperature and the synthesis was completed. The solvent was removed by a rotary evaporator, the ...

Embodiment 2

[0065] The only difference from Example 1 is that the molar ratio of perfluorooctanoyl chloride and oligopolyethyleneimine in the preparation process is 0.5:1, and the prepared amphiphilic fluorinated material is denoted as f 0.5 OEI. The nanoassembly was prepared by the same step (2) as in Example 1.

Embodiment 3

[0067] The only difference from Example 1 is that the molar ratio of perfluorooctanoyl chloride and oligopolyethyleneimine in the preparation process is 1:1, and the prepared amphiphilic fluorinated material is denoted as f 1 OEI. The nanoassembly was prepared by the same step (2) as in Example 1.

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Abstract

The invention provides a nucleic acid delivery carrier, a preparation method and application of the nucleic acid delivery carrier. The nucleic acid delivery carrier is a nanometer self-assembled bodyof an amphiphilic fluorinated material; and the amphiphilic fluorinated material is perfluorooctane-substituted oligomeric polyethyleneimine. According to the nucleic acid delivery carrier provided bythe invention, oligomeric polyethyleneimine and the perfluorooctane material are bonded together, and due to strong hydrophobicity of the perfluor material, not only can the nucleic acid compressingcapability of oligomeric polyethyleneimine be improved, but also the efficiency of cell endocytosis and endosome escape can be improved; positive charges of oligomeric polyethyleneimine not only can be used for electrostatic composition of siRNA, but also can utilize proton sponge effect to promote the endosome escape in the system, and by the combination of electrostatic composition of siRNA andthe endosome escape, the nucleic acid delivery carrier not only has very-high silence efficiency under the serum-free condition, but also can show very high nucleic acid delivery efficiency in the presence of serum, and is expected to be applied in gene therapy based on siRNA or DNA.

Description

technical field [0001] The invention belongs to the technical field of nanomaterials, and relates to a nucleic acid delivery carrier and its preparation method and application, in particular to a fluorinated material-based nucleic acid delivery carrier and its preparation method and application. Background technique [0002] At present, gene therapy has been considered as a powerful means to treat many diseases, including tumors, viral infections and hyperlipidemia. However, due to the negative charge of nucleic acid itself and its large size, it is difficult for them to enter cells by themselves to function; at the same time, free nucleic acid is easily degraded by nucleases in the body and loses its function. Therefore, it is very important to develop a carrier that can protect the nucleic acid from degradation in the in vivo environment and at the same time help the nucleic acid to cross the cell membrane. [0003] The design and preparation of non-viral vectors is a ver...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08J3/03C08J7/00C08J5/18C08G73/02A61K47/34
Inventor 梁兴杰张廷斌郭伟圣
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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