ao9b01410_si_001.pdf (742.89 kB)
Autoinhibitory Feedback Control over Photodynamic Action
journal contribution
posted on 2019-07-17, 18:36 authored by Mediha
Nur Zafer Yurt, Yusuf Cakmak, Gülsüm Tekin, Serdar Karakurt, Sundus Erbas-CakmakIn biology, the activity
of enzymes is usually regulated by feedback
loops, which enables direct communication between enzymes and the
state of the cell. In a similar manner, with the intention to have
automated activity regulation, the therapeutic effect of a photosensitizer
(BOD1) is shown to be reduced through a negative feedback
loop initiated by the photosensitizer. Photodynamic action produces
cytotoxic 1O2 and this reactive oxygen species
reacts with ascorbate, generating H2O2. Peroxide-mediated
oxidation of the photosensitizer auxiliary group leads to the formation
of inactive BOD2 from the parent photosensitizer. BOD1 is shown to accumulate in mitochondria, and cell viability
is shown to decrease significantly with BOD1 compared
to the loop end product, BOD2. Photoinduced enhancement
of fluorescence indicates the formation of inactive BOD2 under cellular conditions, and enhanced fluorescence acts as a reporter
for the activity of the photosensitizer. We present the first example
of PDT autoinactivation, and such a feedback control mechanism would
enable a decrease in post-therapy side effects.