title: On the cutting edge: protease-sensitive prodrugs for the delivery of photoactive compounds.
abstract: Most invasive diseases such as cancer or rheumatoid arthritis are characterized by the upregulation of diverse proteases. Since the early 1970s this phenomenon has been exploited for the selective delivery of a variety of drugs. However, only recently have we and others tried to translate this concept into photomedicine. After a short overview of proteases and the proteolytic imbalance in cancer, we will discuss strategies, their potential and limitations to exploit upregulation of proteases for the selective delivery of in vivo fluorescence reporters and photosensitizers. These strategies can be roughly divided into horizontal, i.e. peptide-based, and vertical, i.e. macromolecular approaches. In the former, a short peptide-based substrate is directly tagged to the photoactive compound or used as a linker between the photoactive compound and a substance that alters its photoactivity. In the latter, the protease sensitive sequence serves as linker between a polymeric carrier and the photoactive payload. Such a macromolecular approach may further benefit from passive targeting through the enhanced penetration and retention effect.
authors.affiliation: School of Pharmaceutical Sciences, University of Lausanne, University of Geneva, Geneva, Switzerland.
authors.forename: Doris
authors.initials: D
authors.lastname: Gabriel
authors.forename: Maria Fernanda
authors.initials: MF
authors.lastname: Zuluaga
authors.forename: Norbert
authors.initials: N
authors.lastname: Lange
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000378:metabolism; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000627:therapeutic use; D011108:Polymers / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy
chemical_list: D017319:Photosensitizing Agents; D011108:Polymers; D011355:Prodrugs; D010447:Peptide Hydrolases