Biomimetic Nanoplatform Based on the Neutrophil Membrane for Targeted Therapy of Spinal Cord Injury

Spinal cord injury (SCI) triggers a cascade of secondary damage, including oxidative stress and neuroinflammation, for which effective treatments remain limited. To address this, we developed a biomimetic nanoplatform, NEU@MPBNPs-HED, consisting of mesoporous Prussian blue nanoparticles (MPBNPs) loaded with hederagenin (HED) and cloaked with neutrophil membranes (NEUm) to enhance lesion targeting and immune evasion.

The physicochemical properties, drug release characteristics, and cellular uptake of NEU@MPBNPs-HED were characterized. Therapeutic efficacy was evaluated in vitro using oxygen-glucose deprivation/reoxygenation (OGD/R) models of neuronal injury and in vivo in a murine spinal cord contusion model. Key outcomes included neuronal survival, oxidative stress, apoptosis, motor recovery, and biodistribution.

In vitro, NEU@MPBNPs-HED significantly improved HT22 neuronal viability by 48.6%, reduced intracellular reactive oxygen species (ROS) by 52.4%, and preserved mitochondrial membrane potential compared with free HED or non-biomimetic controls. Apoptosis was suppressed through modulation of Bax, Bcl-2, and cytochrome C. In vivo, NEU@MPBNPs-HED enhanced Basso Mouse Scale (BMS) scores, improved motor evoked potentials, promoted axonal regeneration (NF200↑), and reduced glial scarring (GFAP↓). Moreover, the oxidative stress marker (MDA), inflammatory indicators (TNF-α, and Ly6G+ cells, and Arg1) were reduced. Biodistribution studies confirmed selective accumulation at the injury site, and histological analyses revealed no systemic toxicity.

The NEU@MPBNPs-HED nanoplatform effectively targeted spinal cord lesions, attenuated oxidative and inflammatory damage, and promoted neurological recovery. These findings highlight the translational potential of biomimetic nanotherapies for treating traumatic central nervous system disorders.