Proteases in cancer drug delivery
Vandooren, J. Opdenakker, G. Edwards, D.R.
Vandooren, J.
Opdenakker, G.
Edwards, D.R.
Publication Date
2016-02-01
End of Embargo
Supervisor
Rights
Peer-Reviewed
Yes
Open Access status
closedAccess
Accepted for publication
2015-12-24
Institution
Department
Awarded
Embargo end date
Collections
Additional title
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.
Version
No full-text in the repository
Citation
Vandooren J, Opdenakker G, Loadman PM and Edwards DR (2016) Proteases in cancer drug delivery. Advanced Drug Delivery Reviews. 97: 144-155.
Link to publisher’s version
Link to published version
Link to Version of Record
Type
Article