The effect and role of carbon atoms in Poly(β-amino ester)s for DNA binding and gene delivery

Corey J. Bishop, Tiia Maaria Ketola, Stephany Y. Tzeng, Joel C. Sunshine, Arto Urtti, Helge Lemmetyinen, Elina Vuorimaa-Laukkanen, Marjo Yliperttula, Jordan J. Green

Research output: Contribution to journalArticle

Abstract

Polymeric vectors for gene delivery are a promising alternative for clinical applications, as they are generally safer than viral counterparts. Our objective was to further our mechanistic understanding of polymer structure-function relationships to allow the rational design of new biomaterials. Utilizing poly(β-amino ester)s (PBAEs), we investigated polymer-DNA binding by systematically varying the polymer molecular weight, adding single carbons to the backbone and side chain of the monomers that constitute the polymers, and varying the type of polymer end group. We then sought to correlate how PBAE binding affects the polyplex diameter and ζ potential, the transfection efficacy, and its associated cytotoxicity in human breast and brain cancer cells in vitro. Among other trends, we observed in both cell lines that the PBAE-DNA binding constant is biphasic with the transfection efficacy and that the optimal values of the binding constant with respect to the transfection efficacy are in the range (1-6) × 104 M -1. A binding constant in this range is necessary but not sufficient for effective transfection.

Original languageEnglish (US)
Pages (from-to)6951-6957
Number of pages7
JournalJournal of the American Chemical Society
Volume135
Issue number18
DOIs
StatePublished - May 8 2013

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint Dive into the research topics of 'The effect and role of carbon atoms in Poly(β-amino ester)s for DNA binding and gene delivery'. Together they form a unique fingerprint.

  • Cite this

    Bishop, C. J., Ketola, T. M., Tzeng, S. Y., Sunshine, J. C., Urtti, A., Lemmetyinen, H., Vuorimaa-Laukkanen, E., Yliperttula, M., & Green, J. J. (2013). The effect and role of carbon atoms in Poly(β-amino ester)s for DNA binding and gene delivery. Journal of the American Chemical Society, 135(18), 6951-6957. https://doi.org/10.1021/ja4002376