Platelet Membrane-Encapsulated Ginkgolide B Biomimetic Nanoparticles for the Treatment of Ischemic Stroke

ACS APPLIED NANO MATERIALS(2023)

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摘要
Stroke is a highly lethal and disabling disease of the central nervous system exacerbated by oxidative stress, inflammation, and ferroptosis. However, the blood-brain barrier makes it extremely difficult for most medications to enter the brain, necessitating extremely high drug concentrations. Thus, we developed platelet-derived nanoparticles to deliver ginkgolide B (GB), a compound that has anti-inflammatory, antioxidative stress, and ferroptosis inhibition properties and assists acute stroke recovery. GB was encapsulated in a platelet membrane (PM) with a particle size of approximately 68.32 +/- 3.7 nm, and the encapsulation efficiency reached 79.43 +/- 6.3%. Experiments showed that PM-derived nanoparticles with GB (PM-GB) increased the activity of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and decreased malondialdehyde(MDA) and reactive oxygen species(ROS) levels in the brain. Additionally, the PM-GB group had higher ferroptosis suppressor protein (GPX4, FSP1) expression, approximately 4-folds, with lower levels of the pro-inflammatory cytokines IL-6, IL-1 ss, and TNF-a, and ferroptosis marker protein (PTGS2) compared with the OGD group. In conclusion, PM-GB reduces ferroptosis and inflammation by inhibiting oxidative stress, which protects neural cells and promotes motor recovery in middle cerebral artery occlusion model rats (MCAO/R).
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关键词
ischemic stroke,nanoparticles,membrane-encapsulated
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