Reactive oxygen species and oxidant microenvironment (ROS)

Reactive oxygen species (ROS) and the oxidant microenvironment refer to a collection of highly reactive oxygen-containing molecules, including superoxide radicals, hydroxyl radicals, and hydrogen peroxide, which characterize the chemical state of a tissue or cellular compartment. Under physiological conditions, ROS act as essential secondary messengers in signal transduction pathways regulating cell growth, differentiation, and the innate immune response (PubMed: 28230001). However, an imbalance between ROS production and the capacity of antioxidant defense mechanisms leads to oxidative stress, a hallmark of various pathologies including cancer, neurodegeneration, and cardiovascular diseases (NIH: PMC4310836). In the context of drug development, the oxidant microenvironment is targeted either through the administration of exogenous antioxidants to mitigate oxidative damage or by utilizing the high ROS levels in diseased tissues to trigger the release of site-specific therapeutic agents from ROS-responsive delivery systems (Nature Reviews Drug Discovery: 10.1038/nrd.2017.243). The primary therapeutic challenge lies in the "antioxidant paradox," where non-selective removal of ROS may impair beneficial signaling or fail to reach the specific intracellular sites of damage, potentially leading to unintended systemic effects.

Other names

Oxidative stressRedox microenvironmentOxygen radicalsPro-oxidantsReactive oxygen species

Direct scavenging of free radicals, enzymatic neutralization of oxidants, or ROS-triggered activation of site-specific prodrugs.