Novel conjugation of tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) with monomethyl auristatin E for efficient antitumor drug delivery

Adv Mater. 2013 Sep 14;25(34):4718-22. doi: 10.1002/adma.201301385. Epub 2013 Jul 12.

Abstract

Monomethyl auristatin E (MMAE) is conjugated with TNF-related apoptosis-inducing ligand (TRAIL) via a linker that is stable in extracellular fluid, while it is cleaved by cathepsin once the conjugate has entered a tumor cell, thus activating the antimitotic mechanism of MMAE. The TRAIL-MMAE conjugate is a conceptually viable therapeutic strategy with improved in vitro antitumor activity, cell circle arrest and specific accumulation in tumor to treat TRAIL-resistant tumors.

Keywords: antitumor agents; biomedical applications; drug delivery; protein modifications; protein-protein interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / toxicity
  • Apoptosis / drug effects
  • Cathepsins / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Drug Carriers / chemistry*
  • Humans
  • MCF-7 Cells
  • Microscopy, Confocal
  • Oligopeptides / chemistry*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / toxicity
  • TNF-Related Apoptosis-Inducing Ligand / chemistry*
  • TNF-Related Apoptosis-Inducing Ligand / genetics
  • TNF-Related Apoptosis-Inducing Ligand / toxicity

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Oligopeptides
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • Cathepsins
  • monomethyl auristatin E