Acid-labile boronate-bridged dextran-bortezomib conjugate with up-regulated hypoxic tumor suppression

Chem Commun (Camb). 2015 Apr 21;51(31):6812-5. doi: 10.1039/c5cc01371b.

Abstract

An acid-labile dextran-bortezomib conjugate (Dex-BTZ), i.e., a macromolecularized proteasome inhibitor, is synthesized by a boron esterification reaction. The prodrug exhibits intracellular acidity-accelerated BTZ release, and up-regulated inhibition efficacies toward hypoxic tumor in vitro and in vivo through both NF-κB- and ERS-mediated apoptosis signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Boronic Acids / chemistry*
  • Bortezomib / chemistry*
  • Bortezomib / pharmacology*
  • Cell Hypoxia / drug effects
  • Cell Line, Tumor
  • Dextrans / chemistry*
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Esterification
  • Humans
  • Hydrogen-Ion Concentration
  • Mice
  • Signal Transduction / drug effects
  • Up-Regulation / drug effects*

Substances

  • Antineoplastic Agents
  • Boronic Acids
  • Dextrans
  • Drug Carriers
  • Bortezomib