Imaging of doxorubicin release from theranostic macromolecular prodrugs via fluorescence resonance energy transfer

J Control Release. 2014 Nov 28:194:189-96. doi: 10.1016/j.jconrel.2014.08.018. Epub 2014 Aug 28.

Abstract

Herein we present a FRET-based theranostic macromolecular prodrug (TMP) composed of (a) dendritic polyglycerol (PG) as polymeric nanocarrier, (b) doxorubicin (Dox) linked via a pH-sensitive hydrazone to (c) a tri-functional linker, and (d) an indodicarbocyanine dye (IDCC) attached in close proximity to Dox. The drug fluorescence is quenched via intramolecular FRET until the pH-sensitive hydrazone bond between the TMP and Dox is cleaved at acidic pH. By measuring its fluorescence, we characterized the TMP cleavage kinetics at different pH values in vitro. The intracellular release of Dox from the carrier was monitored in real time in intact cancer cells, giving more insight into the mode of action of a polymer drug conjugate.

Keywords: Drug delivery; FRET imaging; Intracellular release; Polymer therapeutic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / chemistry*
  • Diagnostic Imaging
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry*
  • Drug Carriers / chemistry
  • Fluorescence Resonance Energy Transfer / methods*
  • Fluorescent Dyes
  • Glycerol / chemistry
  • HeLa Cells
  • Humans
  • Hydrazones / chemistry
  • Hydrogen-Ion Concentration
  • Kinetics
  • Nanoparticles
  • Polymers / chemistry
  • Prodrugs / administration & dosage*
  • Prodrugs / chemistry*

Substances

  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Fluorescent Dyes
  • Hydrazones
  • Polymers
  • Prodrugs
  • polyglycerol
  • Doxorubicin
  • Glycerol