Electrochemical detection of superoxide anion in living systems: Recent trends and clinical implications

Superoxide plays a significant role in maintaining physiological states of living systems, with major roles in eradicating invading microorganisms and in cell signaling. It is regulated intricately by the enzyme superoxide dismutase (SOD), and when not properly regulated it can lead to cascade biological pathways with severe and irreversible damage to biofilms, tissue, and organs, being linked with many neurodegenerative diseases, atherosclerotic and cardiovascular diseases. Therefore, superoxide anion (O₂^•-) detection has a tremendous potential in clinical diagnostics to assess oxidative stress in living cells. This comprehensive review aims to explore, discuss, and analyze recent trends in the electrochemical detection of O₂^•- in living systems, focusing not only on the recognition mechanism for in vitro assays (living cell cultures/tissues) but also on the importance of the electrode design and operational parameters for in vivo measurements (implantable sensors). By analyzing current in vitro/in vivo electrochemical strategies we gather information that is helpful to overcome existing limitations in the dynamic monitoring of O₂^•-, and further improve electrochemical strategies that can be adopted and applied to prevent its negative effect, with an insight into the pathophysiology of neurodegenerative disorders and even cellular malignancies that derive from its accumulation in living systems.