Premium
Polymeric Photosensitizer Prodrugs for Photodynamic Therapy
Author(s) -
Campo Marino A.,
Gabriel Doris,
Kucera Pavel,
Gurny Robert,
Lange Norbert
Publication year - 2007
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2007.00090.x
Subject(s) - photosensitizer , chemistry , pheophorbide a , prodrug , photodynamic therapy , phototoxicity , combinatorial chemistry , biophysics , quenching (fluorescence) , fluorescence , photochemistry , in vitro , biochemistry , organic chemistry , physics , quantum mechanics , biology
A targeting strategy based on the selective enzyme‐mediated activation of polymeric photosensitizer prodrugs (PPP) within pathological tissue has led to the development of agents with the dual ability to detect and treat cancer. Herein, a detailed study of a simple model system for these prodrugs is described. We prepared “first‐generation” PPP by directly tethering the photosensitizer (PS) pheophorbide a to poly‐( l )‐lysine via epsilon amide links and observed that by increasing the number of PS on a polymer chain, energy transfer between PS units improved leading to better quenching efficiency. Fragmentation of the PPP backbone by trypsin digestion gave rise to a pronounced fluorescence increase and to more efficient generation of reactive oxygen species upon light irradiation. In vitro tests using the T‐24 bladder carcinoma cell line and ex vivo experiments using mouse intestines illustrated the remarkable and selective ability of these PPP to fluoresce and induce phototoxicity upon enzymatic activation. This work elucidated the basic physicochemical parameters, such as water solubility and quenching/activation behavior, required for the future elaboration of more adaptable “second‐generation” PPP, in which the PS is tethered to a proteolytically stable polymer backbone via enzyme‐specific peptide linkers. This polymer architecture offers great flexibility to tailor make the PPP to target any pathological tissue known to over‐express a specific enzyme.