Block copolymer and synthesis method thereof, and preparation method of nano particles

A technology of block macromolecules and nanoparticles, which is applied in the fields of block macromolecules and their synthesis, and the preparation of nanoparticles, can solve the problems of affecting the adhesion of polyplex particles with diseased cells, poor targeting effect, etc., so as to improve the circulation efficiency in vivo, The effect of improving the targeting effect

Inactive Publication Date: 2012-11-21
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] The first purpose of the present invention is to provide a block polymer to solve the problem that in the prior art, there are too many positive charges on the outer surface of the surface membrane of Polyplex particles, which affects the attachment of Polyplex particles to diseased cells, and the targeting effect is poor technical issues

Method used

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  • Block copolymer and synthesis method thereof, and preparation method of nano particles
  • Block copolymer and synthesis method thereof, and preparation method of nano particles
  • Block copolymer and synthesis method thereof, and preparation method of nano particles

Examples

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Embodiment 1

[0039] The synthetic method of embodiment 1 block polymer PEG-PCL-maltotriose-COOH

[0040] The synthetic route of block polymer PEG-PCL-maltotriose-COOH is as follows figure 1 shown. The whole reaction is carried out in an anhydrous and oxygen-free environment. Take a certain amount of PEG, polycaprolactone, and stannous octoate into a three-necked bottle, add fresh anhydrous toluene, and stir and react at 120°C for 24 hours. After completion, add diethyl ether to precipitate, then add dichloromethane to dissolve, and then diethyl ether to precipitate, repeat three times to obtain PEG-PCL block polymer.

[0041] Then PEG-PCL was dissolved in methylene chloride, excessive oxalyl chloride was added in the reaction flask, and the PEG-PCL solution was added dropwise in the reaction flask under the condition of anhydrous and oxygen-free ice bath, and returned to Stir at room temperature, remove the remaining oxalyl chloride under reduced pressure after 12 hours, then add dichlor...

Embodiment 2

[0044] The preparation of embodiment 2 nanoparticles

[0045] Take a certain amount of polycationic polymer (take PEI as an example) and plasmid DNA, and to investigate the nanoparticle structure and charge shielding, the polyplexes sample is prepared with a mass ratio of 1:5 (pDNA:PEI), and then the block height Molecules, fully compounded. See specific steps Figure 4 , 5 .

Embodiment 3

[0046] Characterization of Example 3 Nanoparticles

[0047] Nanoparticles prepared according to the above preparation method were characterized by fluorescence colocalization. The specific method was as follows: PEI and FITC were covalently bonded, and the hydrophobic PCL block of the block polymer was labeled with nile red at the same time. The prepared fluorescent particles were immobilized in PVA hydrogel and cross-linked and solidified through repeated "freezing-room temperature" cycles to limit the two-dimensional movement of the particles on the horizontal plane. Observation see Image 6 , red (nile red) and green (FITC) appear and coincide at the same position, verifying the formation of nanoparticles.

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Abstract

The present invention relates to the technical field of biology, and in particular to a block copolymer and a synthesis method thereof, and a preparation method of nano particles. The block copolymer provided by invention comprises a first block, a second block and a third block, which are connected successively. The first block and the third block are hydrophilic blocks, and the second block is a hydrophobic block. Compared with prior art, the block copolymer provided by the invention can effectively shield surface charges of cationic particles like polycation gene complex particles, exclude in vivo circulation barriers of cationic particles, and improve in vivo circulation efficiency, and also can be grafted to a target group to realize pathological cell targeting in vivo, and effectively improve the targeting effect.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a block macromolecule, a synthesis method thereof, and a preparation method of nanoparticles. technical background [0002] siRNA is a 21-25 base pair RNA molecule found in the mechanism of single-celled organisms to resist viral invasion. Single-cell organisms synthesize a complementary siRNA to the mRNA sequence of the invading virus, which actively binds to the mRNA, thereby blocking the replication of the virus. If this one-to-one interference strategy corresponding to pathogen genes is used to develop drugs for the treatment of human diseases, it will fundamentally change the current traditional new drug discovery model and bring about a revolution in drug treatment technology. Because of its unique target specificity, structural designability, and metabolic safety, siRNA has become the first candidate for the next generation of revolutionary new drugs that the scientific commu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G63/91C08G63/664A61K48/00A61K47/34A61K47/42A61K9/14
Inventor 金拓袁伟恩吴飞许丹葛雪梅张奇昕
Owner SHANGHAI JIAO TONG UNIV
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