reactive oxygen species

Overview

Reactive oxygen species (ROS) are chemically reactive oxygen-containing molecules generated endogenously during normal cellular metabolism, especially in mitochondria, and also produced by enzymes such as NADPH oxidases. Major ROS include superoxide, hydrogen peroxide, and hydroxyl radicals. At physiological levels, ROS participate in redox signaling, host defense, and regulation of processes such as proliferation, differentiation, and immune responses. When ROS production exceeds antioxidant capacity, oxidative stress develops, which can damage lipids, proteins, and nucleic acids and contribute to inflammation, mitochondrial dysfunction, ferroptosis, apoptosis, senescence, and tissue injury.

In biomedical research, ROS are studied both as pathogenic mediators and as therapeutic effectors. Excess ROS are implicated in diabetes, diabetic nephropathy, osteoarthritis, acute lung injury, Parkinson’s disease, Alzheimer’s disease, ischemia-reperfusion injury, fibrosis, and cancer progression. Conversely, controlled ROS generation is exploited in photodynamic therapy, sonodynamic therapy, chemodynamic therapy, and some antibacterial strategies. Many recent studies also focus on ROS-responsive or ROS-scavenging nanomaterials, hydrogels, and prodrugs designed to modulate the oxidative microenvironment, often in combination with pathways such as Nrf2/HO-1, NF-κB, NLRP3 inflammasome signaling, PI3K/AKT/mTOR, and ferroptosis-related axes including GPX4 and glutathione metabolism.

Focus of Latest Publications

Recent investigations have positioned reactive oxygen species as a versatile target for managing multiple disease pathologies, spanning malignancies, chronic inflammatory conditions, tissue injuries, and neurodegenerative disorders. Studies have employed two complementary therapeutic strategies: controlled ROS generation to induce cancer cell death and excessive ROS scavenging to mitigate oxidative damage in non-malignant tissues. In oncology, ferroptosis emerges as a central mechanism, with compounds such as cryptotanshinone triggering ROS accumulation and iron-dependent lipid peroxidation in glioma cells, while photodynamic therapy systems utilize photosensitizers to generate cytotoxic ROS upon light activation for targeting tumors and bacterial biofilms. Conversely, in wound healing and tissue regeneration contexts—including diabetic wound infection, periodontal disease, oral ulcers, and acute kidney injury—nanomaterial-based platforms employ GSH-scavenging, catalytic ROS elimination, and antioxidant delivery to suppress oxidative stress and restore tissue integrity.

Advanced nanoplatform designs have achieved spatiotemporal control over ROS dynamics through organelle-targeted delivery and stimulus-responsive mechanisms. Mitochondria-targeted photosensitizers and nanozymes exhibit superior efficacy compared to cytoplasmic counterparts, leveraging the organelle's role in both ROS production and energy metabolism. ROS-responsive drug delivery systems, particularly those incorporating thioketal and diselenide linkers, enable conditional drug release in tumor microenvironments or inflammatory sites characterized by elevated ROS. Mechanotherapeutic frameworks integrate ROS signaling with mechanical stress adaptation, linking ferroptosis susceptibility to autophagy regulation and mitochondrial quality control. In neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease, multifunctional nanoparticles simultaneously suppress ROS generation, chelate metal ions that catalyze Fenton chemistry, inhibit amyloid aggregation, and restore mitochondrial function.

Combined therapeutic modalities that synergize ROS manipulation with immunotherapy have demonstrated enhanced anti-tumor efficacy. Nanoparticles engineered to amplify Intracellular ROS while suppressing the antioxidant glutathione system trigger ferroptosis alongside immunogenic cell death, activating cGAS-STING and dendritic cell maturation to reprogram "cold" tumor microenvironments toward immune responsiveness. Dual-action platforms that simultaneously alleviate acute inflammation through ROS scavenging and promote tissue regeneration through pro-angiogenic or osteogenic signaling address self-perpetuating pathological cycles in chronic wounds and ischemic-reperfusion injuries. These studies collectively establish ROS not merely as a destructive byproduct but as a precisely modulable signaling axis whose targeting—whether through amplification or neutralization—offers broad therapeutic potential across diverse disease contexts.