Metal Armor-Decorated Neutrophil Micromotors with Self-Propelled and Targeting Function for Brain Injury Precise Therapy

Radiation-induced brain injury (RIBI) is a common brain injury following radiotherapy to the head and neck region, which is often accompanied by severe cognitive dysfunction, seriously affecting the quality of life of patients. Studies have established that excessive free radicals produced by radiation are mainly responsible for RIBI. However, there are currently no clinically effective drugs for RIBI treatment. Although nanocatalyst-mediated catalytic therapy is a powerful tool for the treatment of oxidative damage, it is limited by poor targeting and the blood-brain barrier (BBB). Herein, we develop metal armor-decorated neutrophil micromotors (Neumotor) to achieve brain targeting and penetration, which are composed of cryo-shocked neutrophils (CS-Neu) retaining cell membrane integrity and possessing high expression of cell adhesion molecules and chemokine receptors due to a pretreatment strategy, surface thioketal-linked platinum nanoclusters (PtNCs) with catalytic activity. Notably, Neumotor preserves the inflammation-targeting capability of neutrophils and additionally exhibits multienzyme-mimicking activity, reactive oxygen species-responsive release of PtNCs, and self-propulsive functions. Thus, the Neumotor effectively achieves brain targeting and penetration, neutralizes irradiation-caused excess free radicals, mitigates inflammatory damage, BBB disruption, and neuronal injury, ultimately ameliorating cognitive, memory, and spatial perception deficits in RIBI mice. This study not only presents a distinct application for neutrophils but also proposes a feasible catalytic therapy strategy for RIBI.