Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Polycation gene carrier as well as preparation method and application thereof

A gene carrier and polycation technology, applied in the field of biomedical new materials, can solve the problems of poor repeatability and complicated preparation methods, and achieve the effect of simple preparation process and strong repeatability

Active Publication Date: 2018-11-02
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
View PDF6 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] See literature Tian, ​​H.Y.; Chen, X.S. Ultrasensitive pH Triggered Charge / SizeDual-Rebound Gene Delivery System. Nano Lett.2016, 16, 6823-6831. Tian, ​​H.Y; Tang, Z.H.; Zhuang, X.L.; Chen, X.S.; Jing, X.B. Biodegradable synthetic polymers: Preparation, functionalization and biomedical application. Prog. Polym. Sci. 2012, 37, 237-280. Although the carrier reported in the above literature can reduce its cytotoxicity to a certain extent, its preparation method is complicated and the reproducibility is poor

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
  • Polycation gene carrier as well as preparation method and application thereof
  • Polycation gene carrier as well as preparation method and application thereof
  • Polycation gene carrier as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0036] The present invention provides a preparation method of the polycationic gene carrier described in the above technical solution, comprising the following steps:

[0037] a) reacting the activated p-toluenesulfonyl and t-butoxycarbonyl double-protected arginine solution with the grafted skeleton raw material solution, dialyzed, and freeze-dried to obtain a freeze-dried product; the grafting in the grafted skeleton raw material solution The skeleton raw material is selected from dendritic polyamide-amine, hyperbranched polylysine with molecular weight of 2000-100000 g / mol or linear ε-polylysine with molecular weight of 2000-50000 g / mol; the dendritic polyamide-amine is selected from One or more of model PAMAM-G3, model PAMAM-G4 and model PAMAM-G5;

[0038] b) reacting the freeze-dried product with trifluoroacetic acid, and precipitating the reaction product to obtain a polycationic gene carrier.

[0039] The preparation process is simple and reproducible, and plays an imp...

Embodiment 1

[0093] Example 1: Preparation of PAMAM-Arg (Tos)

[0094] (1) Synthesis of PAMAM-Arg(Tos) of G3 generation.

[0095] The PAMAM (200 mg, 0.0289 mmol) of the G3 generation was weighed and dissolved in 4 mL of anhydrous methanol, and a certain amount of p-toluenesulfonyl and tert-butoxycarbonyl double-protected arginine was added according to the designed molar charging ratio (see Table 1). (Boc-Arg(Tos)-OH) was dissolved in anhydrous methanol (dissolved according to 1 g of Boc-Arg(Tos)-OH / 10 mL of methanol). EDCI (2 times the molar equivalent of Boc-Arg(Tos)-OH) and HOBT (2 times the molar equivalent of Boc-Arg(Tos)-OH) were added to the Boc-Arg(Tos)-OH solution to activate the reaction After 1 h, the methanol solution of PAMAM was slowly added to the above mixture, and the reaction was carried out at room temperature for 4 days. The reaction mixture was dialyzed and lyophilized. Then, the lyophilized product was reacted under the condition of trifluoroacetic acid for 4 h, co...

Embodiment 2

[0103] Example 2: Preparation of HBPLL-Arg(Tos)

[0104] (1) Synthesis of HBPLL-Arg(Tos) of HBPLL group with molecular weight of 2000. The weighed HBPLL (200 mg, 0.1 mmol) was dissolved in 4 mL of anhydrous methanol, and a certain amount of Boc-Arg(Tos)-OH was dissolved in anhydrous methanol (according to 1 g Boc- Arg(Tos)-OH / 10mL methanol dissolved). EDCI (2 times the molar equivalent of Boc-Arg(Tos)-OH) and HOBT (2 times the molar equivalent of Boc-Arg(Tos)-OH) were added to the Boc-Arg(Tos)-OH solution at room temperature The activation reaction was carried out for 1 h, and then the methanol solution of PAMAM was slowly added to the above mixture, and the reaction was carried out at room temperature for 4 days. The reaction mixture was dialyzed and lyophilized. Then, the lyophilized product was reacted under the condition of trifluoroacetic acid for 4 h, concentrated in vacuo, precipitated with anhydrous ether, vacuum-dried, dialyzed, lyophilized to obtain a solid produc...

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

No PUM Login to View More

Abstract

The invention provides a polycation gene carrier as well as a preparation method and application thereof. The polycation gene carrier comprises a grafting framework and arginine which is grafted withthe grafting framework and is used for protecting tosyl; raw materials of the grafted raw materials are selected from branch type polyamide-amine, hyperbranched polylysine with the molecular weight being 2000 to 100000 g / mol or linear epsilon-polylysine with the molecular weight being 2000 to 50000 g / mol; the branch type polyamide-amine is selected from one or several kinds of materials of types of PAMAM-G3, PAMAM-G4 and PAMAM-G5. The polycation gene carrier provided by the invention is grafted with the arginine for protecting tosyl onto the specific grafting framework; the transfection efficiency of the compound nanometer particles prepared from the polycation carriers can be obviously improved. In addition, the charge density of the nanometer compound particles can be effectively reduced; the cell toxicity can be further reduced.

Description

technical field [0001] The invention belongs to the technical field of biomedical new materials, and in particular relates to a polycation gene carrier, its preparation method and its application. Background technique [0002] As a new therapeutic tool, gene therapy has gradually attracted people's attention in the treatment of cancer and genetic diseases. Gene therapy refers to a new technology that introduces healthy foreign genes into recipient cells, that is, target cells, to correct or compensate diseases caused by gene defects or abnormalities, so as to achieve therapeutic purposes. [0003] Efficient gene carriers are very important in gene therapy. Among them, the cationic gene carrier has attracted more and more attention. Among traditional cationic gene carriers, PEI25k is the "gold standard" as a cationic gene carrier. Although PEI25k has high transfection efficiency, it has high cytotoxicity, which limits its clinical application [see Lungwitz U, Breunig M, Bl...

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): C12N15/87A61K48/00C08G69/48C08G83/00
CPCA61K48/0041C08G69/48C08G83/004C12N15/87
Inventor 田华雨方华攀林琳陈杰郭兆培陈学思
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com