Synthesis and functional evaluation of DNA-assembled polyamidoamine dendrimer clusters for cancer cell-specific targeting

Chem Biol. 2005 Jan;12(1):35-43. doi: 10.1016/j.chembiol.2004.10.016.

Abstract

We sought to produce dendrimers conjugated to different biofunctional moieties (fluorescein [FITC] and folic acid [FA]), and then link them together using complementary DNA oligonucleotides to produce clustered molecules that target cancer cells that overexpress the high-affinity folate receptor. Amine-terminated, generation 5 polyamidoamine (G5 PAMAM) dendrimers are first partially acetylated and then conjugated with FITC or FA, followed by the covalent attachment of complementary, 5'-phosphate-modified 34-base-long oligonucleotides. Hybridization of these oligonucleotide conjugates led to the self-assembly of the FITC- and FA-conjugated dendrimers. In vitro studies of the DNA-linked dendrimer clusters indicated specific binding to KB cells expressing the folate receptor. Confocal microscopy also showed the internalization of the dendrimer cluster. These results demonstrate the ability to design and produce supramolecular arrays of dendrimers using oligonucleotide bridges. This will also allow for further development of DNA-linked dendrimer clusters as imaging agents and therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carrier Proteins / drug effects*
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • DNA, Complementary / chemistry*
  • DNA, Complementary / pharmacokinetics
  • Drug Design
  • Evaluation Studies as Topic
  • Fluorescein / chemistry
  • Fluorescein / pharmacokinetics
  • Folate Receptors, GPI-Anchored
  • Folic Acid / chemistry
  • Folic Acid / pharmacokinetics
  • Humans
  • Models, Biological
  • Molecular Structure
  • Molecular Weight
  • Oligonucleotides / chemistry
  • Oligonucleotides / pharmacokinetics
  • Phosphates / chemistry
  • Polyamines / chemical synthesis*
  • Polyamines / chemistry
  • Polyamines / pharmacokinetics*
  • Receptors, Cell Surface / drug effects*
  • Receptors, Cell Surface / metabolism
  • Structure-Activity Relationship
  • Surface Properties

Substances

  • Carrier Proteins
  • DNA, Complementary
  • Folate Receptors, GPI-Anchored
  • Oligonucleotides
  • Phosphates
  • Polyamines
  • Receptors, Cell Surface
  • Folic Acid
  • Fluorescein