A complete biodistribution study in naı¨ve (n ¼ 59) and ischemic (n ¼ 51) mice receiving intravenous or intraarterial nanocapsules, with two different magnet devices and imaged from 30 min to 48 h, showed an extraor-dinary advantage of the intraarterial route for brain delivery with a specific improvement in cortical targeting when using a magnetic device in both control and ischemic conditions. Safety was evaluated in ischemic mice (n ¼ 69) showing no signs of systemic toxicity nor increasing mortality, infarct lesions or hemorrhages. In conclusion, the challenging brain delivery of therapeutic nanomaterials could be efficiently and safely overcome with a controlled endovascular admin-istration and magnetic targeting, which could be considered in the context of endovascular interventions for the delivery of multiple treatments for stroke.