Autoinhibitory Feedback Control over Photodynamic Action Mediha Nur Zafer Yurt Yusuf Cakmak Gülsüm Tekin Serdar Karakurt Sundus Erbas-Cakmak 10.1021/acsomega.9b01410.s001 https://acs.figshare.com/articles/journal_contribution/Autoinhibitory_Feedback_Control_over_Photodynamic_Action/8947079 In 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 (<b>BOD1</b>) is shown to be reduced through a negative feedback loop initiated by the photosensitizer. Photodynamic action produces cytotoxic <sup>1</sup>O<sub>2</sub> and this reactive oxygen species reacts with ascorbate, generating H<sub>2</sub>O<sub>2</sub>. Peroxide-mediated oxidation of the photosensitizer auxiliary group leads to the formation of inactive <b>BOD2</b> from the parent photosensitizer. <b>BOD1</b> is shown to accumulate in mitochondria, and cell viability is shown to decrease significantly with <b>BOD1</b> compared to the loop end product, <b>BOD2</b>. Photoinduced enhancement of fluorescence indicates the formation of inactive <b>BOD2</b> 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. 2019-07-17 18:36:57 feedback control mechanism photosensitizer cytotoxic 1 O 2 loop end product PDT Autoinhibitory Feedback Control BOD 2 BOD 1 post-therapy side effects H 2 O 2 reactive oxygen species