Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 05 31 1 7 Mehrshad Ebrahim pour Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran Abdullah Moridikia Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran Ebrahim Salimi-Sabour Department of Pharmacognosy and Traditional Pharmacy, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran 2025 12 26 2026 02 06 Sepsis-induced immunothrombosis is driven in part by dysregulated neutrophil extracellular traps (NETs), yet existing therapies fail to adequately address the oxidative checkpoints that initiate this cascade. This mechanistic Perspective proposes a paradigm shift toward dual-functional inorganic nanomedicine aimed at modulating both inflammation and coagulation. We discuss emerging evidence supporting a “prevention-plus-clearance” strategy employing PEGylated cerium oxide nanoparticles (nanoceria) surface-grafted with DNase I. The inorganic core functions as a prolonged superoxide dismutase–like redox buffer through the regenerative Ce³⁺/Ce⁴⁺ cycle, thereby attenuating reactive oxygen species (ROS)-dominant NETosis pathways rather than universally blocking NET formation. In parallel, the surface-immobilized DNase I facilitates enzymatic degradation of extracellular chromatin scaffolds. We hypothesize that this bio-inorganic combination may address the biphasic nature of sepsis pathogenesis by limiting NET initiation while promoting microvascular de-obstruction. Finally, we outline a translational roadmap required to validate this “circuit-breaker” strategy in vivo, positioning the cerium–NETosis axis as a promising frontier in the management of sepsis-associated coagulopathy. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4724 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4724/2351