Neutrophil membrane-derived nanoparticles protect traumatic brain injury via inhibiting calcium overload and scavenging ROS

The secondary injury is more serious after traumatic brain injury (TBI) compared with primary injury. Release of excessive reactive oxygen species (ROS) and Ca²⁺ influx at the damaged site trigger the secondary injury. Herein, a neutrophil-like cell membrane-functionalized nanoparticle was developed to prevent ROS-associated secondary injury. NCM@MP was composed of three parts: (1) Differentiated neutrophil-like cell membrane (NCM) was synthesized, with inflammation-responsive ability to achieve effective targeting and to increase the retention time of Mn₃O₄ and nimodipine (MP) in deep injury brain tissue via C-X-C chemokine receptor type 4, integrin beta 1 and macrophage antigen-1. (2) Nimodipine was used to inhibit Ca²⁺ influx, eliminating the ROS at source. (3) Mn₃O₄ further eradicated the existing ROS. In addition, NCM@MP also exhibited desirable properties for T₁ enhanced imaging and low toxicity which may serve as promising multifunctional nanoplatforms for precise therapies. In our study, NCM@MP obviously alleviated oxidative stress response, reduced neuroinflammation, protected blood-brain barrier integrity, relieved brain edema, promoted the regeneration of neurons, and improved the cognition of TBI mice. This study provides a promising TBI management to relieve the secondary spread of damage.