Chemotactic Light-harvesting Dual-Lanthanide Nanomotor for Revascularization and Neuroprotection of Ischemic Stroke

Ischemic stroke (IS) presents a major clinical challenge due to brain damage during ischemia/hypoxia and the exacerbated inflammation resulting from the surge of reactive oxygen species (ROS) after reperfusion. Herein, a lanthanide nanomotor (LNM) therapy is reported, which is based on the understanding of chemotaxis and light capture design, and fully exploits the high concurrent functionality of Ln-MOF in IS combined therapy. The LNM nanoparticles (NPs) consist of a targeting peptide layer targeting platelets and neutrophils, and dual-Ln-MOF (Eu/Ce) nanoparticle core loaded with protein drugs, enabling them to actively target thrombi and ischemic brain regions by binding to platelets and neutrophils, thereby achieving local release of thrombolytic drugs. This process can be monitored in real time through Eu ³⁺ luminescence captured by light. Meanwhile, the Ce ⁴⁺ /Ce ³⁺ can further eliminate ROS to alleviate oxidative stress damage to neurons, thereby achieving the combined treatment strategy of revascularization and neuroprotection for IS. Systematic evidence has been provided in the IS mouse model that LNM NPs effectively accumulate in the brain ischemic area and exert therapeutic effects through thrombolysis and improvement of neurological function, providing new ideas for the medical application of lanthanide-based materials in cardiovascular/neurological fields.