Neutrophil-Membrane Biomimetic Nanoparticles Deliver Imperatorin, Cutting Cerebral Infarct Volume by 33% in Rat Stroke Model

Cerebral Ischemia-Reperfusion Injury (CIRI) remains a leading cause of mortality and long-term disability, with current therapeutic strategies often lacking targeted delivery and comprehensive neuroprotection. Oxidative stress and neuroinflammation are key drivers of neuronal damage post-stroke. Traditional drug delivery faces challenges like the blood-brain barrier (BBB) and poor accumulation in ischemic tissue. Biomimetic nanocarriers, particularly those leveraging cell membranes, offer a promising avenue to enhance drug targeting, improve bioavailability, and exert neuroprotective effects by overcoming these delivery hurdles. This study explores a novel nanoplatform to address these gaps.

Researchers synthesized Hollow Mesoporous Silica Nanoparticles (HMSNs), loaded with imperatorin (IMP), then coated with neutrophil cell membranes (NCM) from DMSO-induced HL-60 cells to form NCM/IMP@HMSNs. Nanomaterial characterization confirmed particle properties. In vitro neuroprotection was assessed via oxygen-glucose deprivation/reoxygenation (OGD/R) models in SH-SY5Y cells. In vivo, a rat middle cerebral artery occlusion/reperfusion (MCAO/R) model evaluated ischemic brain accumulation, neurological deficit scores (mNSS), cerebral infarct volume, and mechanisms, comparing NCM/IMP@HMSNs to an untreated MCAO/R group.

The synthesized NCM/IMP@HMSNs nanoparticles exhibited a uniform particle size of approximately ~143 nm and favorable stability, with an imperatorin encapsulation efficiency of 31.84%. In vitro, IMP significantly increased the viability of OGD/R-injured SH-SY5Y cells compared to the model group. In vivo experiments demonstrated that NCM/IMP@HMSNs efficiently accumulated in ischemic brain tissue. > This nanosystem notably decreased neurological deficit scores (mNSS) and reduced cerebral infarct volume by approximately 33.31% compared with the MCAO/R group. Mechanistically, the NCM/IMP@HMSNs activated the Nrf2/ARE/Keap1 pathway, leading to the upregulation of HO-1 expression. This strengthened antioxidant capacity, alleviated the accumulation of cerebral oxidative stress products, and regulated the activities of antioxidant enzymes SOD, GSH, and CAT, while also modulating LDH levels, indicating reduced cellular damage.