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Application of DMP nanoparticles in mRNA delivery

A nanoparticle, the use of technology, applied in the field of medicine, to achieve the effect of high transfection rate and low cytotoxicity

Active Publication Date: 2021-06-22
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004]DMP nanoparticle, namely DOTAP-mPEG-PCL nanoparticle, is a kind of amphiphilic mPEG-PCL composed of DOTAP cationic phospholipid and amphiphilic diblock copolymer Nanoparticles prepared by mixing diblock copolymers. At present, there is no relevant research on the delivery of mRNA by DMP nanoparticles

Method used

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  • Application of DMP nanoparticles in mRNA delivery
  • Application of DMP nanoparticles in mRNA delivery
  • Application of DMP nanoparticles in mRNA delivery

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1 Preparation of DMP cationic nanoparticles / IL-22BP mRNA gene complex

[0044] 1. Preparation of DMP nanoparticles by thin film rotary evaporation

[0045] Cationic lipid (2,3-dioleoyl-propyl)-trimethylamine (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) (structure as figure 1shown) with methyl polyethylene glycol-polycaprolactone (mPEG-PCL) polymer (structure such as figure 2 Shown) (molecular weight is 4000Da, PEG-PCL=2000Da-2000Da) were mixed at a mass ratio of 1:9, and the mixture was dissolved in dichloromethane, and placed on a rotary evaporator at 60°C for 45 minutes film forming. The formed film was taken out and dissolved in deionized water, then shaken in a water bath at 60°C for 5 minutes to obtain a solution of DMP cationic polymer nanoparticles with a specific concentration, which was stored in a 4°C refrigerator for later use.

[0046] 2. Preparation of DMP nanoparticles by microfluidic method

[0047] The cationic lipid (2,3-dioleoyl-propy...

Embodiment 2

[0052] Example 2 Preparation of DMP cationic nanoparticles / Bim mRNA gene complex

[0053] 1. Preparation of DMP nanoparticles by thin film rotary evaporation

[0054] The cationic lipid (2,3-dioleoyl-propyl)-trimethylamine (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) and methyl polyethylene glycol-polycaprolactone (mPEG-PCL ) high molecular weight polymer (molecular weight is 4000Da, PEG-PCL=2000Da-2000Da) is mixed according to the mass ratio of 1:9, and the mixture is dissolved with dichloromethane, and placed on a rotary evaporator with 60 ℃ rotary evaporation Film formed after 45min. The formed film was taken out and dissolved in deionized water, then shaken in a water bath at 60°C for 5 minutes to obtain a solution of DMP cationic polymer nanoparticles with a specific concentration, which was stored in a 4°C refrigerator for later use.

[0055] 2. Preparation of DMP nanoparticles by microfluidic method

[0056] The cationic lipid (2,3-dioleoyl-propyl)-trimethylamin...

Embodiment 3

[0061] Example 3 Preparation of DMP cationic nanoparticles / IL-15 mRNA gene complex

[0062] 1. Preparation of DMP nanoparticles by thin film rotary evaporation

[0063] The cationic lipid (2,3-dioleoyl-propyl)-trimethylamine (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) and methyl polyethylene glycol-polycaprolactone (mPEG-PCL ) high molecular weight polymer (molecular weight is 4000Da, PEG-PCL=2000Da-2000Da) is mixed according to the mass ratio of 1:9, and the mixture is dissolved with dichloromethane, and placed on a rotary evaporator with 60 ℃ rotary evaporation Film formed after 45min. The formed film was taken out and dissolved in deionized water, then shaken in a water bath at 60°C for 5 minutes to obtain a solution of DMP cationic polymer nanoparticles with a specific concentration, which was stored in a 4°C refrigerator for later use.

[0064] 2. Preparation of DMP nanoparticles by microfluidic method

[0065] The cationic lipid (2,3-dioleoyl-propyl)-trimethylam...

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Abstract

The invention belongs to the field of medicines, and particularly relates to the application of DMP (Dimethyl Phthalate) nanoparticles in mRNA (Messenger Ribonucleic Acid) delivery. Aiming at the problem that an efficient and safe carrier is lacked in mRNA delivery at present, the invention provides application of DMP nanoparticles in mRNA delivery, and provides a new delivery carrier for mRNA delivery. The DMP nanoparticles disclosed by the invention are prepared by mixing DOTAP cationic phospholipid and an amphiphilic double-block copolymer (mPEG-PCL). The DMP nanoparticles provided by the invention have low cytotoxicity and high transfection rate when being used for delivering mRNA, and have a very good prospect. Meanwhile, a compound formed by compounding the DMP nanoparticles and mRNA can effectively inhibit the growth of colon cancer tumor tissues in vivo, and a new strategy is provided for disease treatment.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to the application of DMP nanoparticles in mRNA delivery. Background technique [0002] Treatment for colorectal cancer consists of surgical resection and adjuvant chemotherapy, or a combination of targeted therapy and chemotherapy. In addition, gene therapy is also a potential treatment option, which mainly introduces exogenous nucleic acid into target cells through vectors, changes gene expression, and treats diseases. Messenger RNA is a class of RNA molecules that can be translated into cellular proteins. Many existing studies have found that the introduction of mRNA into cells can treat genetic diseases or act as anti-tumor vaccines. Since mRNA functions in the cytoplasm, the nuclear envelope, which is the main obstacle for pDNA, can be avoided, as well as the risk of insertional mutagenesis. In addition, mRNA has fewer structural elements than plasmids, making delivery le...

Claims

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Application Information

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IPC IPC(8): A61K47/60A61K47/59A61K47/69A61K31/7105A61K48/00A61P35/00A61P1/00A61P11/00A61P15/14
CPCA61K47/60A61K47/593A61K47/6935A61K31/7105A61P35/00A61P1/00A61P11/00A61P15/14
Inventor 门可段醒妹魏于全
Owner SICHUAN UNIV