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Degradable polymer based on ring opening polymerization of valerolactone derivative and production method and application thereof

A technology of degrading polymers and ring-opening polymerization, which can be applied to other methods of inserting foreign genetic materials, recombinant DNA technology, etc., and can solve the problems of single polyester carrier structure, far-flung transfection efficiency, and unfavorable modification.

Active Publication Date: 2019-08-30
BEIJING NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, their transfection efficiency is still far from that of viral vectors, and the reported polyester vectors have a single structure, which is not conducive to modification

Method used

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  • Degradable polymer based on ring opening polymerization of valerolactone derivative and production method and application thereof
  • Degradable polymer based on ring opening polymerization of valerolactone derivative and production method and application thereof
  • Degradable polymer based on ring opening polymerization of valerolactone derivative and production method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] A degradable polymer based on ring-opening polymerization of valerolactone derivatives, the structural formula (I) of the compound is as follows:

[0049]

[0050] In formula (I), R 1 Is a substituted or unsubstituted macrocyclic polyamine [12]aneN 3 group, R 2 is a sulfur-containing substituent, R 3 is a substituted or unsubstituted phenyl group, m and n are positive integers greater than or equal to 10.

[0051] Wherein, when the degradable polymer is represented by a compound of formula (I-1):

[0052]

[0053] Among them, R 1 for R 2 for The polymer with n=m=10 is designated as polymer B1a; R 1 for R 2 for n=20, m=10 is recorded as polymer B1b.

[0054] When the degradable polymer is represented by a compound of formula (I-2):

[0055]

[0056] Among them, R 1 for R 2 for The polymer with n=20 and m=10 is designated as polymer B2a.

[0057] When the degradable polymer is represented by a compound of formula (I-3):

[0058]

[005...

Embodiment 2

[0073] Prepare solutions of different concentrations of B1a / DOPE, B1b / DOPE, B2a / DOPE, B3a / DOPE and B3b / DOPE (1:2, molar ratio) respectively, and form a complex with pGL-3 plasmid DNA at 37°C Incubate for 0.5 h, and then add it into different gel wells to conduct DNA agarose gel retardation experiments to obtain the aggregation of DNA by different concentrations of polymers.

[0074] figure 1 A~1E are the agarose gel retardation experiment results of the pGL-3DNA of polymer B1a / DOPE of the present invention, B1b / DOPE, B2a / DOPE, B3a / DOPE and B3b / DOPE respectively; figure 1 It can be concluded that the polymer formed based on valerolactone ring-opening polymerization of the present invention can effectively condense DNA to form nanoparticles, and can be used as a non-viral gene carrier.

Embodiment 3

[0076] Polymer B2a and its cationic liposomes formed with DOPE at 1:0.5, 1:1, 1:2 (molar ratio) and PGL-3DNA were incubated at 37°C for 30 minutes before administration, and the cultured HeLa was added In the cells, act for 5 hours, suck out the compound, and then replace the cell culture medium with fresh DMEM culture medium containing 10% FBS and culture for 48 hours. After removing the medium, add 120 μL of cell lysate, lyse the cells, measure the luminescence intensity and protein content, take PEI 25k as the standard, and the luminescence intensity per milligram of protein (RLU / mg protein) indicates the transfection efficiency of compound B2a .

[0077] figure 2 It is the luciferase expression result of the compound B2a of the present invention and its liposome formed with DOPE as a non-viral gene carrier in HeLa cells at different concentrations and different ratios of B2a / DOPE; PEI 25k is used as a reference.

[0078] figure 2 The middle X-axis is B2a and its diffe...

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Abstract

The invention discloses a degradable polymer based on ring opening polymerization of a valerolactone derivative and a production method and application thereof. The compound is mainly produced throughMichael reaction, ROP reaction and thio-ene click reaction, and the structure of the compound is identified through nuclear magnetism and mass spectrometry. According to the degradable polymer, through testing means of gel electrophoresis, dynamic light scattering, SEM and the like, the fact that the degradable polymer can condense DNA is proven, and the diameters of formed nanoparticles are allsmaller than 200 nm. An in-vitro transfection experiment proves that lipidosome formed by the degradable polymer and dioleoyl phosphatidylethanolamine (DOPE) can be used as a non-viral gene vector.

Description

technical field [0001] The invention relates to a non-viral gene carrier, in particular to a degradable polymer based on ring-opening polymerization of valerolactone derivatives and its preparation method and application. Background technique [0002] Gene therapy has great potential in the treatment of genetic defects, cancer and other diseases. It is to introduce the target gene into the diseased cells of the patient and make it express. In gene therapy, because the cell membrane contains a lot of negatively charged glycoproteins, glycolipids, etc., and the cells contain nucleases, etc., it is difficult to express naked DNA in cells. Therefore, the development of safe and effective gene carriers has become the focus of research. At present, non-viral gene vectors have received more attention than viral vectors. Because it can not only overcome the problems of immunogenicity, harsh preparation and storage brought by viral gene vectors, but also has the advantages of low ...

Claims

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Application Information

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IPC IPC(8): C08G63/91C12N15/87
CPCC08G63/912C12N15/87
Inventor 卢忠林刘旭英刘名轩马乐乐
Owner BEIJING NORMAL UNIVERSITY
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