Synergistic effects on gene delivery - co-formulation of small disulfide-linked dendritic polycations with Lipofectamine 2000 (TM)

John G. Hardy, Christine S. Love, Nathan P. Gabrielson, Daniel W. Pack, David K. Smith*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)
212 Downloads (Pure)

Abstract

This paper describes the application of gene delivery vectors based on connecting together two well-defined low-generation poly(L-lysine) (PLL) dendrons using a disulfide-containing linker unit. We report that the transfection ability of these vectors in their own right is relatively low, because the low-generation number limits the endosomal buffering capacity. Importantly, however, we demonstrate that when applied in combination with Lipofectamine 2000 (TM), a vector from the cationic lipid family, these small cationic additives significantly enhance the levels of gene delivery (up to four-fold). Notably, the cationic additives have no effect on the levels of transfection observed with a cationic polymer, such as DEAE dextran. We therefore argue that the synergistic effects observed with Lipofectamine 2000 (TM) arise as a result of combining the delivery advantages of two different classes of vector within a single formulation, with our dendritic additives providing a degree of pH buffering within the endosome. As such, the data we present indicate that small dendritic structures, although previously largely overlooked for gene delivery owing to their inability to transfect in their own right, may actually be useful well-defined additives to well-established vector systems in order to enhance the gene delivery payload.

Original languageEnglish
Pages (from-to)789-793
Number of pages5
JournalOrganic & biomolecular chemistry
Volume7
Issue number4
Early online date12 Jan 2009
DOIs
Publication statusPublished - 2009

Keywords

  • IN-VITRO
  • DNA-BINDING
  • MULTIVALENT DENDRONS
  • PLASMID DNA
  • GLYCOL)-BLOCK-POLY(L-LYSINE) DENDRIMER
  • ANTISENSE OLIGONUCLEOTIDES
  • GOLD NANOPARTICLES
  • NONVIRAL CARRIERS
  • LYSINE DENDRIMERS
  • CATIONIC POLYMER

ASJC Scopus subject areas

  • Chemistry(all)
  • Molecular Medicine
  • Biomaterials

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