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Hydrophobic-group-modified polyethyleneimine derivative and application thereof

A polyethylenimine, hydrophobic group technology, applied in the use of vectors to introduce foreign genetic material, recombinant DNA technology, etc., can solve problems such as low transfection efficiency, and achieve high transfection efficiency, low cytotoxicity, and efficient delivery. Effect

Inactive Publication Date: 2012-12-05
SUZHOU UNIV
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  • 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

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  • 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...

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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

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08G73/04C12N15/63
Inventor 钟志远刘兆忠郑蒙孟凤华
Owner SUZHOU UNIV
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