Cation polymer capable of removing positive charges through oxidative response, a preparation method and application

Patent metadata

Field	Value
Publication number	US-10640592-B2
Application number	US-201515768470-A
Country	US
Kind code	B2
Filing date	Oct 13, 2015
Priority date	Oct 13, 2015
Publication date	May 5, 2020
Grant date	May 5, 2020

Abstract

Disclosed are the cation polymers capable of removing their positive charges in oxidative conditions, preparation methods, and applications as gene delivery carriers. The oxidation-responsive unit is the p-(boronic acid or ester)benzylammonium, which upon oxidation eliminates p-hydroxymethlphenol and thus converts in a tertiary amine. Compared with the prior art, different from a common quaternary amination carrier, the synthesized charge reversal type gene delivery carrier for oxidative response of the present invention has a large quantity of positive charges and can well coat a DNA, but the positive charges can be removed under the condition of intracellular oxidation when the charge reversal type gene delivery carrier enters a cell, a charge reverse is triggered, the positive charges turn to negative charges, and the DNA is quickly released for transfection. The carrier is efficient, low in toxicity, and good in application prospect.

First claim

What is claimed is:

1. A cationic polymer capable of removing positive charges through oxidative response, comprising the following moiety:

wherein:
R 1 and R 2 are independently selected from the group consisting of C 1-6 alkyl or aryl;
R 3 and R 4 are independently selected from the group consisting of hydrogen, C 1-6 alkyl or acyl; and
m is a positive integer from 1 to 4;
wherein the cationic polymer is obtained from reactions between polyacrylate, polymethacrylate or other primary or secondary amino-containing polymers and a compound containing benzylboronic acid or ester; and
wherein the primary or secondary amino-containing polymers comprise poly[2-(N,N-disubstituted-amino)ethyl acrylate], polyethyleneimine (PEI) and poly(amidoamine) dendrimers (PAMAM).

2. The cationic polymer of claim 1 , wherein R 3 and R 4 are selected from hydrogen, acetyl or formyl, and R 1 and R 2 are methyl or ethyl.

3. The cationic polymer of claim 1 , wherein the polymer is used for the delivery of deoxyribonucleic acids and oligonucleotides.

4. The cationic polymer of claim 1 , wherein the polymer is used for the delivery of taxol.

5. The polymer of claim 1 , wherein the polymer comprises an anion, which is bromide or chloride ion.

Assignees

• Univ Zhejiang

Inventors

• Shen Youqing
• Liu Xin
• Tang Jianbin
• Liu Xiangrui

Classifications

• C08G73/0206

  Polyalkylene(poly)amines · CPC title

• A61K48/0041

  the non-active part being polymeric · CPC title

• A61K47/59 Primary

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes · CPC title

• C12N15/88

  using microencapsulation, e.g. using {amphiphile} liposome vesicle · CPC title

• C08F120/34

  Esters containing nitrogen {, e.g. N,N-dimethylaminoethyl (meth)acrylate} · CPC title