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Autoinhibitory Feedback Control over Photodynamic Action.

Mediha Nur Zafer Yurt1,1, Yusuf Cakmak1,1,1, Gülsüm Tekin2

  • 1Institute of Science, Biotechnology Graduate Program, Research and Development Center for Diagnostic Kits, Department of Bioengineering, and Department of Molecular Biology and Genetics, Konya Food and Agriculture University, Konya 42080, Turkey.

ACS Omega
|August 29, 2019
PubMed
Summary

Researchers developed a novel photosensitizer (BOD1) that self-inactivates via a feedback loop, reducing side effects. This photodynamic therapy autoinactivation mechanism uses reactive oxygen species to create an inactive form (BOD2).

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Area of Science:

  • Biochemistry
  • Photodynamic Therapy (PDT)
  • Cell Biology

Background:

  • Enzyme activity in biology is typically regulated by feedback loops for cellular communication.
  • Photosensitizers are used in photodynamic therapy, but their activity can lead to side effects.

Purpose of the Study:

  • To investigate the potential for automated activity regulation of a photosensitizer (BOD1) using a negative feedback loop.
  • To demonstrate the first example of photodynamic therapy autoinactivation.

Main Methods:

  • Investigated the reaction of cytotoxic 1O2 produced by BOD1 photodynamic action with ascorbate to generate H2O2.
  • Analyzed the peroxide-mediated oxidation of BOD1's auxiliary group, forming the inactive BOD2.
  • Utilized fluorescence enhancement as a reporter for BOD2 formation under cellular conditions.

Main Results:

  • BOD1 accumulates in mitochondria, leading to a significant decrease in cell viability.
  • The inactive product, BOD2, shows reduced cytotoxicity compared to BOD1.
  • Photoinduced fluorescence enhancement confirms the formation of inactive BOD2 within cells.

Conclusions:

  • The study presents the first example of photodynamic therapy autoinactivation mediated by a negative feedback loop.
  • This feedback mechanism effectively reduces the therapeutic effect of the photosensitizer, potentially decreasing post-therapy side effects.
  • Enhanced fluorescence serves as a reliable indicator of photosensitizer activity and feedback loop progression.