Proteases in cancer drug delivery

Jennifer Vandooren, Ghislain Opdenakker, Paul M. Loadman, Dylan R Edwards

Research output: Contribution to journalArticle

65 Citations (Scopus)
12 Downloads (Pure)

Abstract

Whereas protease inhibitors have been developed successfully against hypertension and viral infections, they have failed thus far as cancer drugs. With advances in cancer profiling we now better understand that the tumor "degradome" (i.e. the repertoire of proteases and their natural inhibitors and interaction partners) forms a complex network in which specific nodes determine the global outcome of manipulation of the protease web. However, knowing which proteases are active in the tumor micro-environment, we may tackle cancers with the use of Protease-Activated Prodrugs (PAPs). Here we exemplify this concept for metallo-, cysteine and serine proteases. PAPs not only exist as small molecular adducts, containing a cleavable substrate sequence and a latent prodrug, they are presently also manufactured as various types of nanoparticles. Although the emphasis of this review is on PAPs for treatment, it is clear that protease activatable probes and nanoparticles are also powerful tools for imaging purposes, including tumor diagnosis and staging, as well as visualization of tumor imaging during microsurgical resections.

Original languageEnglish
Pages (from-to)144-155
Number of pages12
JournalAdvanced Drug Delivery Reviews
Volume97
Early online date3 Jan 2016
DOIs
Publication statusPublished - 1 Feb 2016

Keywords

  • Prodrug
  • Metalloproteinase
  • Urokinase
  • Legumain
  • Cathepsin
  • Nanoparticles

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