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

A technology of block polymer and synthesis method, applied in the field of preparation of nanoparticles, block polymer and its synthesis, can solve the problems of poor targeting effect, affecting the adhesion of polyplex particles with diseased cells, etc., so as to improve the targeting effect, The effect of improving the efficiency of circulation in the body

Inactive Publication Date: 2014-04-30
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

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1 Synthesis method of 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. A certain amount of PEG, polycaprolactone, and stannous octoate are added to a three-necked flask, and freshly prepared anhydrous toluene is added. The reaction is stirred at 120°C for 24 hours. After completion, add ether for precipitation, then add dichloromethane to dissolve, and then use ether for precipitation, repeat three times to obtain PEG-PCL block polymer.

[0041] Then dissolve PEG-PCL in dichloromethane, add excess oxalyl chloride to the reaction flask, add the PEG-PCL solution dropwise to the reaction flask under the condition of anhydrous and oxygen-free ice bath, and return to Stir at room temperature. After 12 hours, remove the remaining oxalyl chloride under reduced pressure. Then add dichloromethane to dissolv...

Embodiment 2

[0044] Example 2 Preparation of nanoparticles

[0045] Take a certain amount of polycationic polymer (taking PEI as an example) and plasmid DNA. Due to the investigation of nanoparticle structure and charge shielding, the mass ratio 1:5 (pDNA:PEI) is selected to prepare polyplexes samples, and then block high Molecule, fully compounded. See the specific steps Figure 4 , 5 .

Embodiment 3

[0046] Example 3 Characterization of Nanoparticles

[0047] The nanoparticles prepared according to the above preparation method were characterized by fluorescence co-localization. The specific method is as follows. The PEI and FITC are covalently bonded, and the hydrophobic PCL block of the block polymer is labeled with nile red. The prepared fluorescent particles are fixed in the 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. See the observation Image 6 , Red (nile red) and green (FITC) appear and overlap 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 polymer and a method for synthesizing the same and a method for preparing nanoparticles. technical background [0002] siRNA is a 21-25 base pair RNA molecule, found in the mechanism of single-celled organisms to resist virus invasion. Single-cell organisms synthesize a complementary siRNA against the mRNA sequence of the invading virus, and actively bind to the mRNA, thereby blocking virus replication. If this interference strategy corresponding to pathogen genes is used to develop drugs to treat human diseases, it will fundamentally change the current traditional model of new drug discovery and bring about a revolution in drug treatment technology. Because of its unique target specificity, structural design and metabolic safety, siRNA has become the first candidate for the next generation of revolutionary new drugs that the scientific community is generally optimistic about. H...

Claims

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Application Information

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Patent Type & Authority Patents(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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