Reconsidering azobenzene as a component of small-molecule hypoxia-mediated cancer drugs: A theranostic case study

Peter Verwilst, Jiyou Han, Jiyeong Lee, Sora Mun, Hee Gyoo Kang, Jong Seung Kim

Research output: Contribution to journalArticlepeer-review

90 Citations (Scopus)


An azobenzene scaffold serves as both a fluorescence quencher and nitrogen mustard deactivator in a mitochondrial targeting unit bearing theranostic drug delivery system (DDS). The DDS exhibited a tissue selectivity for tumors with aggressive phenotypes, and the efficient in vitro and in vivo azoreduction under hypoxia conditions resulted in bright fluorescence at the tumor site as well as the in situ activation of the prodrug. In vivo therapeutic experiments demonstrated a significant reduction in tumor growth versus number of controls and ex vivo tissue analysis confirmed tissue normalization with strongly reduced angiogenic markers and suppressed cell proliferation. Mechanistic insight of the DDS's mode of action was gained by gene and protein expression experiments, aided by a proteomic analysis, revealing the circumvention of cellular drug resistance pathways as well as the normalization of Slit-Robo signaling, and the involvement of granzyme-triggered mitochondria-mediated apoptosis. Overall, the combined high sensitivity and synthetic ease as well as excellent therapeutic response suggests a revival of the azobenzene class of hypoxia activated drugs, especially applied to theranostics, is warranted.

Original languageEnglish
Pages (from-to)104-114
Number of pages11
Publication statusPublished - 2017 Jan 1


  • Azobenzene
  • Cancer
  • Drug targeting
  • Hypoxia
  • Theranostics

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials


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