Acta Chimica Sinica ›› 2014, Vol. 72 ›› Issue (5): 569-576.DOI: 10.6023/A14030185 Previous Articles     Next Articles



郝莹, 张洋, 何金林, 尚修娟, 张明祖, 倪沛红   

  1. 苏州大学材料与化学化工学部 江苏省先进功能高分子材料设计及应用重点实验室 苏州 215123
  • 投稿日期:2014-03-15 发布日期:2014-04-17
  • 通讯作者: 倪沛红
  • 基金资助:

    受国家自然科学基金(Nos. 21374066,21074078)、江苏省基础研究计划(自然科学基金)——滚动资助项目(No. BK2011045)、江苏高校优势学科建设项目资助.

Synthesis and Characterization of PEGylated Brush-type Polycation Modified with Galactosamine

Hao Ying, Zhang Yang, He Jinlin, Shang Xiujuan, Zhang Mingzu, Ni Peihong   

  1. College of Chemistry, Chemical Engineering and Materials Science, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, Soochow University, Suzhou 215123
  • Received:2014-03-15 Published:2014-04-17
  • Supported by:

    Projects supported by the National Natural Science Foundation of China (Nos. 21374066 and 21074078), the Natural Science Foundation of Jiangsu Province for Rolling Support (No. BK2011045), the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions.

Gene therapy has been generally regarded as a promising treatment for numerous hard curable diseases, such as cancer, genetic and infectious diseases. Seeking a safe and efficient vector plays the most challenging role in gene therapy. In the past decades, non-viral polycation has attracted much more attentions as a promising gene vector due to their good biocompatibility, high condensation ability, as well as easily-adjustable and controlled structures. In the present work, a series of galactosamine (Gal)-conjugated brush-type cationic copolymer P(PEGMEMA-co-PEGMA-Gal)-b-PDMAEMA were prepared via a combination of two-step atom transfer radical polymerization (ATRP) technique and polymer reaction. Firstly, random copolymerization of poly(ethylene glycol)methyl ether methacrylate (PEGMEMA) and poly(ethylene glycol) methacrylate (PEGMA) was carried out to yield the copolymer P(PEGMEMA-co-PEGMA), which was further used as a macroinitiator to polymerize 2-(N,N-dimethylamino)ethyl methacrylate (DMAEMA), producing the cationic copolymer P(PEGMEMA-co-PEGMA)-b-PDMAEMA. Finally, the brush-type copolymer P(PEGMEMA-co-PEGMA-Gal)-b- PDMAEMA was obtained by the modification of pendent hydroxyl groups with galactosamine using N,N'-carbonyldiimi-dazole (CDI) as the coupling agent. PDMAEMA is a well-known pH-sensitive polycation and has been widely applied for non-viral gene delivery, while the brush-type hydrophilic chains provide the carrier with favorable biocompatibility, prolonged blood circulation time, and reduced non-specific adsorption of proteins. PDMAEMA block would be partially protonated to afford some hydrophobic domains and positive charges at neutral condition, which can bind with DNA via electrostatic interaction to form polycation/DNA polyplex. The Gal moiety on the surface made the polyplex easily recognized by asialoglycoprotein receptors (ASGPRs) over-expressing hepatoma cells and internalized via a receptor-mediated endocytosis process. The chemical structures, molecular weights and molecular weight distributions of P(PEGMEMA-co-PEGMA-Gal)-b-PDMAEMA copolymer were characterized by 1H NMR, FT-IR, and GPC measurements. The DNA binding capacity of this copolymer was investigated by agarose gel electrophoresis and zeta potential measurements, which indicated that DNA migration could be completely retarded when the N/P ratio was higher than 1.5. The DLS analysis demonstrated that the polyplex held an average particle size of about 106 nm. In addition, in vitro cytotoxicity (MTT assay) and transfection assays were also examined, the results showed that the copolymer possessed relatively lower cytotoxicity than branched PEI (25 kDa), and the transfection of polyplex into HepG2 cells was more efficient than that of HeLa cells studied by live cell imaging system owing to specific ligand-receptor interactions between Gal and ASGPRs on the surface of HepG2 cells. This study presents a facile strategy for the preparation of biocompatible polymeric micelles that will act as a promising platform for hepatoma-targeting delivery of genes.

Key words: galactosamine, brush-type copolymer, ATRP, gene delivery