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Exploiting the Cellular Redox‐Control System for Activatable Photodynamic Therapy
Author(s) -
Gharibi Nima,
Kailass Karishma,
Beharry Andrew A.
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800585
Subject(s) - photodynamic therapy , protoporphyrin ix , chemistry , redox , fluorescence , photothermal therapy , cancer cell , biophysics , reactive oxygen species , combinatorial chemistry , cancer , biochemistry , nanotechnology , materials science , medicine , biology , physics , organic chemistry , quantum mechanics
Photodynamic therapy (PDT) has been successfully used to treat a variety of cancers. However, one drawback has been the adverse side effects experienced by patients during therapy, as a result of the destruction of normal tissues upon irradiation. Herein, we describe the design, synthesis and characterisation of a photosensitiser to overcome this issue that, in addition to light, is also dependent on the overactive redox system present in cancer cells for its activation. Our probe consists of the photosensitiser, protoporphyrin IX, and a FRET‐based quencher dye, BHQ‐3, on a scaffold containing a disulfide bond. The close proximity of BHQ‐3 to protoporphyrin IX quenches its ability to fluoresce and produce reactive oxygen species, whereas nonenzymatic or enzymatic reduction can recover its native properties. We further demonstrate its ability to be activated in cancer cells in a thiol‐dependent manner and destroy breast and lung cancer cells upon red‐light irradiation.