Activated biomimetic nanoprobe for precision MRI of cerebral ischemia

Ischemic stroke requires rapid and accurate imaging for timely intervention. However, conventional MRI contrast agents are limited by insufficient blood-brain barrier (BBB) penetration and nonspecific background signals. Here, we report a macrophage membrane-camouflaged, pH-responsive MnO nanoplatform (MnO@MM NPs) that integrates inflammation- targeted brain accumulation with acidic microenvironment-triggered T₁ signal activation. The MnO@MM NPs exhibited well-defined physicochemical properties and favorable biocompatibility. Owing to the biomimetic membrane coating, the nanoparticles showed enhanced BBB transport and increased accumulation in ischemic brain regions without altering systemic biodistribution. Under mildly acidic conditions, MnO@MM NPs enabled controlled Mn^2 + release, resulting in significantly enhanced longitudinal relaxivity and an "off-on" T₁ MRI activation behavior. In a transient middle cerebral artery occlusion model, MnO@MM NPs achieved rapid and spatially extensive contrast enhancement within ischemic regions while remaining largely inactive in normal brain tissue. Compared with the control group, MnO@MM NPs exhibited accelerated signal activation and broader lesion coverage, reflecting improved lesion accessibility and more efficient coupling between nanoparticle delivery and microenvironment-responsive activation. Collectively, this current study establishes a biomimetic and activatable MRI nanoplatform that enables spatiotemporally coordinated imaging of cerebral ischemia, providing a promising strategy for the development of precision neuroimaging probes for early-stage stroke.