Neutrophil membrane-camouflaged ruthenium single-atom nanozymes precisely eliminate neutrophil extracellular traps to reprogram redox-immune microenvironment in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) causes severe secondary brain injury driven by excessive reactive oxygen species (ROS) deposition, neutrophil extracellular traps (NETs) formation, and persistent neuroinflammation. The pathological peptidylarginine deiminase 4 (PAD4)-mediated NETosis and aberrant crosstalk between pro-inflammatory neutrophils and M1-polarized microglia collectively therapeutic strategies remain lacking. Herein, we fabricate a bone marrow-derived neutrophils membrane-camouflaged ruthenium single-atom nanozyme (Ru-SAN) loaded with the PAD4 inhibitor GSK484 (Ru-SAN/G@M) for precise ICH treatment. Taking advantage of neutrophil-derived inflammatory homing properties, Ru-SAN/G@M efficiently crosses the blood brain barrier and specifically accumulates at neuroinflammatory lesions. The Ru single-atom sites exert excellent antioxidant enzyme-mimetic activity to eliminate excess ROS, while encapsulated GSK484 inhibits PAD4 activation and blocks pathological NET formation. This dual modulation disrupts detrimental neutrophil-microglia inflammatory communication, reverses microglial M1 polarization toward the protective M2 phenotype, and alleviates neuronal apoptosis and secondary brain damage. This study develops an integrated catalytic and pharmacological strategy to remodel the redox-immune microenvironment, providing a promising therapeutic paradigm for ICH and other ROS-related neuroinflammatory disorders.