Reducible poly(2-dimethylaminoethyl methacrylate): Synthesis, cytotoxicity, and gene delivery activity

Ye Zi You, Devika Soundara Manickam, Qing Hui Zhou, David Oupický

Research output: Contribution to journalArticlepeer-review

143 Scopus citations

Abstract

Reducible polycations represent promising carriers of therapeutic nucleic acids. Oligomers of 2-dimethylaminoethyl methacrylate (DMAEMA) containing terminal thiol groups were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using difunctional chain transfer agent. Reducible poly(DMAEMA) (rPDMAEMA) was synthesized by oxidation of the terminal thiol groups, forming a polymer with disulfide bonds in the backbone. Physico-chemical properties of DNA polyplexes of rPDMAEMA were evaluated by dynamic and static light scattering methods, revealing lower structural density and DNA content than control PDMAEMA polyplexes. Cytotoxicity and transfection activity of rPDMAEMA-based DNA polyplexes were evaluated in vitro. In comparison with control PDMAEMA, only minimum toxic effects of rPDMAEMA were observed in a panel of cell lines. Transfection activity was tested in B16F10 mouse melanoma and six human pancreatic cancer cell lines. rPDMAEMA polyplexes showed a comparable or better activity than control PDMAEMA polyplexes.

Original languageEnglish (US)
Pages (from-to)217-225
Number of pages9
JournalJournal of Controlled Release
Volume122
Issue number3
DOIs
StatePublished - Oct 8 2007
Externally publishedYes

Keywords

  • Cytotoxicity
  • Gene delivery
  • RAFT polymerization
  • Reducible polycations
  • Transfection

ASJC Scopus subject areas

  • Pharmaceutical Science

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