Autoinhibitory Feedback Control over Photodynamic Action.

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 () is shown to be reduced through a negative feedback loop initiated by the photosensitizer. Photodynamic action produces cytotoxic O and this reactive oxygen species reacts with ascorbate, generating HO. Peroxide-mediated oxidation of the photosensitizer auxiliary group leads to the formation of inactive from the parent photosensitizer. is shown to accumulate in mitochondria, and cell viability is shown to decrease significantly with compared to the loop end product, . Photoinduced enhancement of fluorescence indicates the formation of inactive 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.