Novel cationic polyaspartamide with covalently linked carboxypropyl-trimethyl ammonium chloride as a candidate vector for gene delivery
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- 作者：Mariano Licciardi ; Monica Campisi ; Gennara Cavallaro ; Bianca Carlisi and Gaetano Giammona
- 关键词：Synthetic gene vectors ; Polycation ; Polyplexes ; α ; β ; -poly(N-2-hydroxyethyl)-d ; l-aspartamide (PHEA) ; 3-(carboxypropyl) trimethyl ammonium chloride
- 刊名：European Polymer Journal
- 出版年：2006
- 出版时间：April 2006
- 年：2006
- 卷：42
- 期：4
- 页码：823-834
- 全文大小：268 K
文摘
The non-viral gene vector properties of a protein-like polymer, the α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA) were investigated after its derivatization with 3-(carboxypropyl)trimethyl-ammonium chloride (CPTA) as molecule bearing cationic groups, in order to obtain stable polycations able to condense DNA. PHEA was firstly functionalized with hydrazide pendant groups by reaction with hydrazine monohydrate (HYD), obtaining the polyhydrazide α,β-poly(N-2-hydroxyethyl/carbazate)-d,l-aspartamide (PHEAȁ3;HYD). In this paper we reported that polymer functionalization degree can be easily modulated by varying reaction conditions, so allowing us to produce two PHEA derivatives at different molar percentage of hydrazide groups. Subsequently, condensation reaction of PHEAȁ3;HYD copolymers with CPTA yielded α,β-poly(N-2-hydroxyethyl)-N-carbazate[N 32;-(3-trimethylammonium chloride)propylhydrazide]-d,l-aspartamide (PHEAȁ3;HYDȁ3;CPTA) polycation derivatives. In vitro studies were carried out to evaluate polycations ability to complex DNA and to protect it from nuclease degradation. Obtained results demonstrated the good efficiency of our new PHEA-polycations derivatives, PHEAȁ3;HYDȁ3;CPTA, to complex and condense genomic material even at very low polycation/DNA weight ratio.