Bioelectronic Approaches for On-Demand Generation of Reactive Oxygen Species

Abstract: Reactive oxygen species (ROS) are an integral part of our lives. They perform essential functions in our biology and are, due to their high oxidative power, key molecules in advanced oxidation processes in industrial applications such as treatment of wastewater. Likewise, they play a crucial role as active intermediates in chemodynamic or photodynamic therapy of cancer. ROS, such as hydrogen peroxide (H2O2) or hydroxyl radicals (OH·), are derived from molecular oxygen (O2), and represent relatively more reactive oxidants with respect to parent O2.At the cellular level, ROS are produced primarily in mitochondria and among others take part in cell signaling and maintaining redox homeostasis. However, when exceeding a certain threshold, ROS can lead to oxidative stress and consequently to cardiovascular and neurodegenerative diseases, as well as cell death. Yet, the ability of modulating the generation of ROS externally gives the possibility to treat certain diseases as well. Advanced oxidation processes such as photoinduced generation of ROS and Fenton-like processes consisting of reactions of H2O2 with transition metal ions are particularly potent and tunable approaches of ROS generation.The aim of this thesis is to expand the range of applications for advanced oxidation processes, and it includes device and electrode fabrication and characterization for local ROS generation and delivery.In paper 1, we exploited naturally-sourced lignins, which share critical structural features with known photocatalysts, to photochemically reduce O2 to H2O2 with simultaneous degradation of the biopolymer, when irradiated with UV light. By adding electron donors, the autoxidation of the lignins was reduced and H2O2 generation partially increased. By showing the possibility to destructively photooxidize lignins to produce H2O2 we contribute to new developments of valorization of lignins and engineering solutions.In paper 2, we created an electro-Fenton device which electrochemically generates H2O2 and simultaneously dissolves chromium. Chromium ions and H2O2 are cytotoxic in their own right, but also can react with each other to form highly oxidizing hydroxyl radicals. We demonstrated the ability of these electrochemically-generated species to induce cell death in a metastatic human skin cancer cell line. In paper 3 we spun the concept of paper 2 further and demonstrated biphasic electro-Fenton reaction on a single stainless steel electrode and showed the generation of hydroxyl radicals with autoluminescense measurements in situ. In paper 4, we investigated the anodic contributions of electrodes in physiological conditions in regards of ROS formation to shed light onto possible electrochemically induced processes contributing to the disintegration of cells by current treatment. Studying the application of oxygen reduction reaction, electro-fenton processes, and oxidation processes in physiological environment leads to a better understanding of electrochemical processes and could further simplified, cheap and locally applied direct current tissue ablation in anti-tumor treatment with decreased systemic side effects.In summary this thesis elaborates various novel methods of on-demand ROS generation. Paper 1 is a photoinduced process, while papers 2-4 introduce various methods of electrochemical ROS generation via combinations of cathodic (oxygen reduction reactions) and anodic (metal corrosion, direct water oxidation) processes.

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