Functionalization of Chitosan via Atom Transfer Radical Polymerization for Gene Delivery

Authors

  • Yuan Ping,

    1. State Key Laboratory of Chemical Resource Engineering, College of Materials Science and Engineering Beijing University of Chemical Technology, 100029 (P. R. China)
    2. Division of Bioengineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, 117574 (Singapore)
    Search for more papers by this author
  • Cheng-De Liu,

    1. Division of Bioengineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, 117574 (Singapore)
    Search for more papers by this author
  • Gu-Ping Tang,

    1. Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou, 310028 (P. R. China)
    Search for more papers by this author
  • Jian-Shu Li,

    1. College of Polymer Science and Engineering, Sichuan University, Chengdu, 610065 (P. R. China)
    Search for more papers by this author
  • Jun Li,

    1. Division of Bioengineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, 117574 (Singapore)
    Search for more papers by this author
  • Wan-Tai Yang,

    1. State Key Laboratory of Chemical Resource Engineering, College of Materials Science and Engineering Beijing University of Chemical Technology, 100029 (P. R. China)
    Search for more papers by this author
  • Fu-Jian Xu

    Corresponding author
    1. State Key Laboratory of Chemical Resource Engineering, College of Materials Science and Engineering Beijing University of Chemical Technology, 100029 (P. R. China)
    • State Key Laboratory of Chemical Resource Engineering, College of Materials Science and Engineering Beijing University of Chemical Technology, 100029 (P. R. China).
    Search for more papers by this author

Errata

This article is corrected by:

  1. Errata: Correction: Functionalization of Chitosan via Atom Transfer Radical Polymerization for Gene Delivery Volume 21, Issue 12, 2174, Article first published online: 16 June 2011

Abstract

It is of crucial importance to modify chitosan-based polysaccharides in the designing of biomedical materials. In this work, atom transfer radical poly­merization (ATRP) was employed to functionalize chitosan in a well-controlled manner. A series of new degradable cationic polymers (termed as PDCS) composed of biocompatible chitosan backbones and poly((2-dimethyl amino)ethyl methacrylate) (P(DMAEMA)) side chains of different length were designed as highly efficient gene vectors via ATRP. These vectors, termed as PDCS, exhibited good ability to condense plasmid DNA (pDNA) into nanoparticles with positive charge at nitrogen/phosphorus (N/P) ratios of 4 or higher. All PDCS vectors could well protect the condensed DNA from enzymatic degradation by DNase I and they displayed high level of transfectivity in both COS7, HEK293 and HepG2 cell lines. Most importantly, in comparison with high-molecular-weight P(DMAEMA) and ‘gold-standard’ PEI (25 kDa), the PDCS vectors showed considerable buffering capacity in the pH range of 7.4 to 5, and were capable of mediating much more efficient gene transfection at low N/P ratios. At their own optimal N/P ratios for trasnsfection, the PDCS/pDNA complexes showed much lower cytotoxicity. All the PDCS vectors were readily to be degradable in the presence of lysozyme at physiological conditions in vitro. These well-defined PDCS polymers have great potentials as efficient gene vectors in future gene therapy.

Ancillary