UV photoresponsive hyperbranched poly(belta-amino esters) with efficient gene delivery capability, and preparation method and application thereof

A light-responsive, hyperbranched polymerization technology, which can be used in medical preparations with inactive ingredients, other methods of inserting foreign genetic materials, and pharmaceutical formulations. It can solve problems such as high cytotoxicity, improve transfection efficiency, promote interaction, enhancing the effect of electrostatic interactions

Active Publication Date: 2020-02-04
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Existing gene carriers are limited by their structure and require a high mass ratio to effectively condense nucleic acids, which may result in high cytotoxicity

Method used

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  • UV photoresponsive hyperbranched poly(belta-amino esters) with efficient gene delivery capability, and preparation method and application thereof
  • UV photoresponsive hyperbranched poly(belta-amino esters) with efficient gene delivery capability, and preparation method and application thereof
  • UV photoresponsive hyperbranched poly(belta-amino esters) with efficient gene delivery capability, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] The method for preparing UV photoresponsive hyperbranched poly-β-amino ester is as follows:

[0068] Add 2,6-dimethylnitrobenzene (15g, 0.15mol) to 95 o C NaOH solution was stirred evenly, then potassium permanganate (66 g, 0.418 mol) was added, and then refluxed for 24 h; then the mixture was cooled to room temperature, filtered, and the filtrate was adjusted to pH 1 with hydrochloric acid to obtain the white solid product 2- Nitro-1,3-phthalic acid.

[0069] Under the condition of ice bath, 1.0 mol borane (in tetrahydrofuran complex, 400mL) was added into 2-nitro-1, 3-benzenedicarboxylic acid (16.0 g, 76 mmol) and dissolved in The mixture was obtained in a solution of tetrahydrofuran in water; the mixture was heated to room temperature and stirred for 48h; then methanol (40mL) was added dropwise, filtered and dried under vacuum, then the dry matter was dissolved in ethyl acetate and washed with saturated NaCl solution (4 × 100 mL), and the organic phase was dried wi...

Embodiment 2

[0072] 2-Nitro-1,3-diacrylate m-xylylene (174.6 mg, 0.6 mmol), trimethylolpropane triacrylate (74 mg, 0.25 mmol) and 4-amino-1-butanol ( 89 mg, 1 mmol) were mixed, and reacted at 60°C for 8 h without solvent; then added (3-aminopropyl)-4-methylpiperazine (157 mg, 1 mmol) in dichloromethane mL), reacted at room temperature for 12 hours; then settled three times with glacial ether, and removed the solvent under vacuum to obtain a yellow viscous oil, that is, UV photoresponsive hyperbranched poly-β-amino ester (BPAE-NB), with a total yield of 72%. . Deuterated chloroform for NMR, with figure 2 Its nuclear magnetic spectrum, x is 9-11, y is 8-10, z is 7-9. The chemical structural formula of BPAE-NB is as follows:

[0073]

[0074] The polymer was treated with UV light (365 nm, 20 mW / cm2, 5 min) and the molecular weight of the polymer before and after treatment was determined by GPC.

Embodiment 3

[0084] Example 3 Preparation, characterization and performance of DNA-loaded nanomedicine

[0085] Prepare the poly-β-amino ester (BPAE-NB) of Example 2 with an acetate buffer solution (pH = 5.2) at a concentration of 1 mg / mL and DNA (plasmid DNA, a plasmid containing luciferase expression extracted from Escherichia coli, a conventional product ) DEPC aqueous solution at a concentration of 0.1 mg / mL; then DNA and poly-β-amino ester were mixed in different weight ratios (1 / 0.5, 1 / 1, 1 / 5, 1 / 10 and 1 / 15), and the mixture was vortexed 10 sec, followed by incubation at 37°C for 30 min to form poly-β-amino ester / DNA complexes. Load the sample into the sample well by 1% agarose gel electrophoresis, run at 100 V for 40 min, stain with ethidium bromide, and image with a gel imaging system to measure the encapsulation efficiency of DNA.

[0086] DNA and poly-β-amino ester were mixed in different weight ratios (1 / 0.2, 1 / 0.5, 1 / 1, 1 / 2 and 1 / 5), the mixture was vortexed for 10 seconds, an...

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Abstract

The invention provides UV photoresponsive hyperbranched poly(belta-amino esters) with the efficient gene delivery capability, and a preparation method and application thereof. The polymer is polymerized by an 'A2+B3+C2' Michael addition method, and thus the polymer is provided with a hyperbranched structure. Compared with a linear structure, the branched structure can enhance the interaction between the polymer and nucleic acid molecules, significantly improves the gene condensation capability, and meanwhile can increase cell uptake by enhancing the interaction with a cell membrane. A main chain of the polymer is provided with a UV responsive group, and under UV light irradiation, the poly(belta-amino esters) can be rapidly degraded after cell endocytosis to release an entrapment gene; andefficient gene transfection is realized, and material toxicity is lowered. The properties of the poly(belta-amino esters) enable the poly(belta-amino esters) to have great development prospects in the field of biomedical materials, especially the field of gene delivery.

Description

technical field [0001] The invention relates to the field of gene loading and delivery, in particular to a UV light-responsive hyperbranched poly-β-amino ester with high-efficiency gene delivery capability and its preparation method and application, and is applied to the transfection of DNA and siRNA. Background technique [0002] Gene carrier materials are important tools for loading genes, delivering them into target cells and successfully expressing them. Gene carrier materials can be divided into two categories: viral vectors and non-viral vectors. Viral vectors have the advantages of high transfection efficiency, but their own shortcomings such as high immunogenicity, high risk of carcinogenesis, and low gene loading seriously restrict their application and development. Based on this, non-viral vectors have gradually gained attention and development. Commonly used non-viral vectors include liposomes, nanoparticles, cationic polymers, and polysaccharides. Due to the l...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G73/02A61K47/34C12N15/87
CPCC08G73/0213C08G73/0206A61K47/34C12N15/87A61K31/7105C08G83/005A61K47/42
Inventor 殷黎晨曹德盛段善洲
Owner SUZHOU UNIV
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