Hydrophobic-group-modified polyethyleneimine derivative and application thereof

A polyethyleneimine and hydrophobic group technology, applied in the direction of using vectors to introduce foreign genetic material, recombinant DNA technology, etc., can solve the problem of low transfection efficiency, achieve high transfection efficiency, increase transfection efficiency, and low cell toxic effect

Inactive Publication Date: 2011-09-14
SUZHOU UNIV
View PDF3 Cites 17 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, PEI has varying degrees of toxicity and has lower transfection efficiencies compared to viral vectors

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Hydrophobic-group-modified polyethyleneimine derivative and application thereof
  • Hydrophobic-group-modified polyethyleneimine derivative and application thereof
  • Hydrophobic-group-modified polyethyleneimine derivative and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1: Synthesis of Trimethoxybenzyl-Trihydroxyethane (TMB-THME)

[0044] 1,1,1-Trihydroxyethane (THME, 6.667 g, 55.5 mmol) and p-toluenesulfonic acid (0.5278 g, 2.775 mmol) were first dissolved in 100 mL tetrahydrofuran at 50 °C, and then 2, 4, 6-Trimethoxybenzaldehyde (TMB, 3.63 g, 18.5 mmol) and 7.5 g of 4 Å molecular sieves were added. After reacting overnight at 50°C, 7 mL of triethylamine was added and diluted with 75 mL of dichloromethane. The molecular sieves were filtered off and washed with dichloromethane, and spin-dried under reduced pressure to obtain a white solid. The solid was dissolved in dichloromethane and extracted three times with 0.1 M pH 8.0 PB buffer solution. The organic phase was collected and dried overnight with anhydrous magnesium sulfate. The next day Magnesium sulfate was filtered off and spin-dried under reduced pressure to obtain a white solid, which was dried in a vacuum oven for 2 days. Yield: 54.6%.

[0045] The NMR characteriz...

Embodiment 2

[0046] Embodiment two: p-nitrophenyl chloroformate ( p -NC) Activated trimethoxybenzyl-trihydroxyethane (TMB-THME-PC)

[0047] The white product TMB-THME (2.31 g, 7.8 mmol) in Example 1 was dissolved in 70 mL of dichloromethane, and triethylamine (2.36 g, 23.4 mmol), pyridine (0.60 g, 7.8 mmol) , p-nitrophenyl chloroformate (1.565 g, 9.13 mmol) was added thereto, and reacted overnight at room temperature. After the reaction was completed, the reaction liquid was added to 300 mL of anhydrous diethyl ether (precipitated triethylamine hydrochloride), and the filtrate was filtered to precipitate into ice n-hexane, and a light brown solid was obtained by filtration, which was dried in vacuum for 2 days. Yield: 60%.

[0048] The NMR characterization of TMB-THME-PC is shown in the appendix figure 2 B: 1 H NMR (400 MHz, CDCl 3 ): d 8.30 (d, 2H), d 7.42 (d, 2H), d 6.10 (s, 2H), d 6.00 (s, 1H), d 4.77 (s, 2H), d 4.05 (d, 2H), d 3.83 (s, 6H), d 3.79 (s, 3H), d 3.68 (d, 2H), d 0.9...

Embodiment 3

[0049] Embodiment three: modified 10 kDa PEI (PEI (10 kDa)- g -(TMB-THME) n )Synthesis

[0050] 10 kDa PEI (0.3 g, 6.97 mmol) was dissolved in 6 mL of dichloromethane, TMB-THME-PC (0.497 g, 1.1 mmol) was dissolved in CH 2 Cl 2 , under the protection of nitrogen, TMB-THME-PC was added dropwise to 10 kDa PEI in dichloromethane solution, after the addition was complete, the reaction was carried out at room temperature for 24 hours. After the reaction, the reaction solution was first precipitated three times in glacial ether, and then the product was dissolved in secondary water, dialyzed with MWCO 3500 dialysis bag to remove p-nitrophenol, and freeze-dried for 2 days to obtain a yellowish solid. Get PEI (10 kDa)- g -(TMB-THME) 9 , yield 73%.

[0051] where PEI (10 kDa)- g -(TMB-THME) 9 The NMR characterization is as follows image 3 : 1 H NMR (400 MHz, CDCl 3 ): d 6.07 (s, 2H), d 5.93 (s, 1H), d 4.50 (s, 2H), d 3.97 (s, 2H), d 3.81 (s, 6H), d 3.75 (s, 3H), d 3.57 (s, 2H...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
number average molecular weightaaaaaaaaaa
number average molecular weightaaaaaaaaaa
particle diameteraaaaaaaaaa
Login to view more

Abstract

The invention belongs to the field of polymer modification, and particularly relates to an acid-sensitive hydrophobic modified polyethyleneimine and application thereof as a gene vector. The derivative contains an acid-sensitive acetal functional group; and specifically, the derivative is an acetal-molecular trimethoxy benzylacetal-trihydroxy ethylacetal (TMB-THME) modified polyethyleneimine derivative, named polyethyleneimine-(trimethoxy benzylacetal-trihydroxy ethane). The polyethyleneimine-(trimethoxy benzylacetal-trihydroxy ethane) provided by the invention enhances the DNA (deoxyribonucleic acid) compounding capability of PEI (polyetherimide) and the interaction with cells, can convert a hydrophobic group into a hydrophilic group in an endosome, and implements the dissociation of theDNA compound and the intracellular release of the DNA; and the cytotoxicity is low.

Description

technical field [0001] The invention belongs to the field of polymer modification, and in particular relates to an acid-sensitive hydrophobically modified polyethyleneimine and its application as a gene carrier. Background technique [0002] Gene therapy has broad application prospects for the treatment of many human diseases such as cancer, cardiovascular disease, infectious disease, genetic disease and so on. For successful gene therapy, the therapeutic gene must be targeted to the lesion site. Viral vectors are currently the most effective gene carriers. However, viral vectors have some inherent disadvantages, such as immunogenicity, poor targeting, limited DNA loading, and complex production and use procedures. In recent years, non-viral gene vectors, especially polycationic vectors, have attracted extensive attention of researchers because they have many advantages compared with viral vectors. For example, the structure and properties of the vector can be controlled,...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C08G73/04C12N15/63
Inventor 钟志远刘兆忠郑蒙孟凤华
Owner SUZHOU UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap