Molecularly imprinted nanoparticles hitchhiking on neutrophils for precise treatment of ischemic stroke

Ischemic stroke (IS), the most prevalent type of stroke worldwide, is associated with a variety of complex processes, including oxidative stress, apoptosis, and ferroptosis. Recent findings indicate that inhibiting iron overload as a key regulatory mechanism of ferroptosis profoundly influences the pathogenesis and treatment of IS. In addition, enhanced blood-brain barrier (BBB) penetration and precise targeting of the ischaemic site contribute to improved therapeutic outcomes in IS. In this study, we developed FeSO₄ templated-molecularly imprinted nanoparticles (MINPs) with high-affinity recognition of ferrous ions (Fe²⁺). MINPs exhibited physicochemical properties that perfectly match the polarity and condensed structure of Fe²⁺, resulting in the effective and specific clearance of Fe²⁺ through efficient and selective adsorption both in vivo and in vitro. Moreover, MINPs hitchhiked circulating neutrophils, thereby facilitating their penetration through BBB and enhancing targeted delivery to the ischemic brain. Our results, supported by transcriptomic analysis, further elucidated the molecular mechanisms by which MINPs significantly inhibit ferroptosis while concurrently regulating apoptosis and inflammation, thereby conferring marked neuroprotection against IS.