A biomimic anti-neuroinflammatory nanoplatform for active neutrophil extracellular traps targeting and spinal cord injury therapy

Traumatic spinal cord injury (SCI) always leads to severe neurological deficits and permanent damage. Neuroinflammation is a vital process of SCI and have become a promising target for SCI treatment. However, the neuroinflammation-targeted therapy would hinder the functional recovery of spinal cord and lead to the treatment failure. Herein, a biomimic anti-neuroinflammatory nanoplatform (DHCNPs) was developed for active neutrophil extracellular traps (NETs) targeting and SCI treatment. The curcumin-loaded liposome with the anti-inflammatory property acted as the core of the DHCNPs. Platelet membrane and neutrophil membrane were fused to form the biomimic hybrid membrane of the DHCNPs for hijacking neutrophils and neutralizing the elevated neutrophil-related proinflammatory cytokines, respectively. DNAse I modification on the hybrid membrane could achieve NETs degradation, blood spinal cord barrier, and neuron repair. Further studies proved that the DHCNPs could reprogram the multifaceted neuroinflammation and reverse the SCI process via nuclear factor kappa-B (NF-κB) pathway. We believe that the current study provides a new perspective for neuroinflammation inhibition and may shed new light on the treatment of SCI. Broad-spectrum anti-inflammatory nanotherapeutics (DHCNPs) are fabricated for combination therapy of spinal cord injury. DHCNPs have the ability to regulate the intricate neuroinflammatory microenvironment by neutralizing proinflammatory cytokines, selectively cleaving neutrophil extracellular traps to promote revascularization and neurorestoration, while also alleviating oxidative stress. [Display omitted] •DHCNPs, a biomimetic anti-neuroinflammatory nanoplatform, effectively targets NETs and treats spinal cord injury (SCI).•DHCNPs integrate a hybrid membrane from platelet and neutrophil, enabling neutrophil hijacking and cytokine neutralization.•DHCNPs degrade NETs, repair blood-spinal cord barrier, and reprogram neuroinflammatory response for SCI treatment.