Biodegradable poly(amine-co-ester) terpolymers for targeted gene delivery

Jiangbing Zhou, Jie Liu, Christopher J. Cheng, Toral R. Patel, Caroline E. Weller, Joseph M. Piepmeier, Zhaozhong Jiang, W. Mark Saltzman

Research output: Contribution to journalArticle

267 Scopus citations

Abstract

Many synthetic polycationic vectors for non-viral gene delivery show high efficiency in vitro, but their usually excessive charge density makes them toxic for in vivo applications. Here we describe the synthesis of a series of high molecular weight terpolymers with low charge density, and show that they exhibit efficient gene delivery, some surpassing the efficiency of the commercial transfection reagents Polyethylenimine and Lipofectamine 2000. The terpolymers were synthesized via enzyme-catalyzed copolymerization of lactone with dialkyl diester and amino diol, and their hydrophobicity adjusted by varying the lactone content and by selecting a lactone comonomer of specific ring size. Targeted delivery of the pro-apoptotic TRAIL gene to tumour xenografts by one of the terpolymers results in significant inhibition of tumour growth, with minimal toxicity both invitro and in vivo. Our findings suggest that the gene delivery ability of the terpolymers stems from their high molecular weight and increased hydrophobicity, which compensates for their low charge density.

Original languageEnglish (US)
Pages (from-to)82-90
Number of pages9
JournalNature Materials
Volume11
Issue number1
DOIs
StatePublished - Jan 2012

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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    Zhou, J., Liu, J., Cheng, C. J., Patel, T. R., Weller, C. E., Piepmeier, J. M., Jiang, Z., & Saltzman, W. M. (2012). Biodegradable poly(amine-co-ester) terpolymers for targeted gene delivery. Nature Materials, 11(1), 82-90. https://doi.org/10.1038/nmat3187