Design, synthesis, and biological functionality of a dendrimer-based modular drug delivery platform

Bioconjug Chem. 2011 Apr 20;22(4):679-89. doi: 10.1021/bc100360v. Epub 2011 Mar 22.

Abstract

A modular dendrimer-based drug delivery platform was designed to improve upon existing limitations in single dendrimer systems. Using this modular strategy, a biologically active platform containing receptor mediated targeting and fluorescence imaging modules was synthesized by coupling a folic acid (FA) conjugated dendrimer with a fluorescein isothiocyanate (FITC) conjugated dendrimer. The two different dendrimer modules were coupled via the 1,3-dipolar cycloaddition reaction ("click" chemistry) between an alkyne moiety on the surface of the first dendrimer and an azide moiety on the second dendrimer. Two simplified model systems were also synthesized to develop appropriate "click" reaction conditions and aid in spectroscopic assignments. Conjugates were characterized by (1)H NMR spectroscopy and NOESY. The FA-FITC modular platform was evaluated in vitro with a human epithelial cancer cell line (KB) and found to specifically target the overexpressed folic acid receptor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Click Chemistry
  • Dendrimers / chemical synthesis
  • Dendrimers / chemistry
  • Dendrimers / metabolism*
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism*
  • Drug Delivery Systems*
  • Drug Design*
  • Fluorescent Dyes / chemistry
  • Folate Receptors, GPI-Anchored / analysis*
  • Folate Receptors, GPI-Anchored / biosynthesis
  • Folic Acid / chemistry
  • Folic Acid / metabolism*
  • Humans
  • Isothiocyanates / chemistry
  • KB Cells
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Structure
  • Surface Properties
  • Tumor Cells, Cultured

Substances

  • Dendrimers
  • Drug Carriers
  • Fluorescent Dyes
  • Folate Receptors, GPI-Anchored
  • Isothiocyanates
  • isothiocyanic acid
  • Folic Acid