Synthesis of multifunctional PAMAM-aminoglycoside conjugates with enhanced transfection efficiency

Bioconjug Chem. 2013 Nov 20;24(11):1928-36. doi: 10.1021/bc4003635. Epub 2013 Nov 4.

Abstract

The development of multifunctional vectors for efficient and safe gene delivery is one of the major challenges for scientists working in the gene therapy field. In this context, we have designed a novel type of aminoglycoside-rich dendrimers with a defined structure based on polyamidoamine (PAMAM) in order to develop efficient, nontoxic gene delivery vehicles. Three different conjugates, i.e., PAMAM G4-neamine, -paromomycin, and -neomycin, were synthesized and characterized by nuclear magnetic resonance (NMR) and MALDI analysis. The conjugates were found to self-assemble electrostatically with plasmid DNA, and unlike neamine conjugate, each at its optimum showed increased gene delivery potency compared to PAMAM G4 dendrimer in three different cell lines, along with negligible cytotoxicity. These results all disclosed aminoglycosides as suitable functionalities for tailoring safe and efficient multifunctional gene delivery vectors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides / chemistry*
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Dendrimers / chemistry*
  • Genetic Vectors / chemistry*
  • Genetic Vectors / genetics*
  • HeLa Cells
  • Humans
  • Molecular Conformation
  • Nylons / chemistry*
  • Plasmids / chemistry
  • Plasmids / genetics
  • Transfection / methods*
  • Tumor Cells, Cultured

Substances

  • Aminoglycosides
  • Dendrimers
  • Nylons
  • PAMAM-G4