High level of detrimental factors including
reactive oxygen species (ROS) and inflammatory
cytokines accumulated in the
infarct core and their erosion to salvageable penumbra are key pathological cascades of
ischemia-reperfusion injury in
stroke. Few
neuroprotectants can remodel the hostile microenvironment of the
infarct core for the failure to interfere with dead or biofunctionally inactive dying cells. Even
ischemia-reperfusion injury is temporarily attenuated in the penumbra by medications; insults of detrimental factors from the core still erode the penumbra continuously along with
drug metabolism and clearance. Herein, a strategy named "nanobuffer" is proposed to neutralize detrimental factors and
buffer destructive erosion to the penumbra. Inspired by neutrophils' tropism to the
infarct core and affinity to inflammatory
cytokines,
poly(lactic-co-glycolic acid) (PLGA) nanoparticles are coated with neutrophil membrane to target the
infarct core and absorb inflammatory
cytokines; α-
lipoic acid is decorated on the surface and
cannabidiol is loaded for ROS scavenging and neuroprotection, respectively, to construct the basic unit of the nanobuffer. Such a nanobuffer exerts a comprehensive effect on the
infarct area via detrimental factor neutralization and
cannabidiol-induced neuroprotection. Besides, the nanobuffer can possibly be enhanced by dynamic ROP (ring-opening-polymerization)-induced membrane cross-fusion among closely adjacent units in vivo. Systematic evaluations show significant decrease of detrimental factors in the core and the penumbra, reduced
infarct volume, and improved neurological recovery compared to the untreated group of
stroke rats.