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An Activatable Photosensitizer Targeting Human NAD(P)H: Quinone Oxidoreductase 1
Author(s) -
Digby Elyse M.,
Sadovski Oleg,
Beharry Andrew A.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201904607
Subject(s) - photosensitizer , chemistry , quinone , cytotoxicity , photodynamic therapy , nad+ kinase , cytotoxic t cell , singlet oxygen , photochemistry , oxidoreductase , prodrug , enzyme , cancer research , biophysics , stereochemistry , biochemistry , in vitro , oxygen , biology , organic chemistry
Human NAD(P)H: Quinone Oxidoreductase 1 (hNQO1) is an attractive enzyme for cancer therapeutics due to its significant overexpression in tumors compared to healthy tissues. Its unique catalytic mechanism involving the two‐electron reduction of quinone‐based compounds has made it a useful target to exploit in the design of hNQO1 fluorescent chemosensors and hNQO1‐activatable‐prodrugs. In this work, hNQO1 is exploited for an optical therapeutic. The probe uses the photosensitizer, phenalenone, which is initially quenched via photo‐induced electron transfer by the attached quinone. Native phenalenone is liberated in the presence of hNQO1 resulting in the production of cytotoxic singlet oxygen upon irradiation. hNQO1‐mediated activation in A549 lung cancer cells containing high levels of hNQO1 induces a dose‐dependent photo‐cytotoxic response after irradiation. In contrast, no photo‐cytotoxicity was observed in the normal lung cell line, MRC9. By targeting hNQO1, this scaffold can be used to enhance the cancer selectivity of photodynamic therapy.