The increasing use of mechanical thrombectomy in stroke management has opened the window to local intraarterial brain delivery of therapeutic agents. In this context, the use of nanomedicine could further improve the delivery of new treatments for specific brain targeting, tracking and guidance. In this study we take advantage of this new endovascular approach to deliver biocompatible poly(D-L-lactic-co-glycolic acid) (PLGA) nanocapsules functionalized with superparamagnetic iron oxide nanoparticles and Cy7.5 for magnetic targeting, magnetic resonance and fluorescent molecular imaging. A complete biodistribution study in naïve (n = 59) and ischemic (n = 51) mice receiving intravenous or intraarterial nanocapsules, with two different magnet devices and imaged from 30 min to 48 h, showed an extraordinary 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 = 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 administration and magnetic targeting, which could be considered in the context of endovascular interventions for the delivery of multiple treatments for stroke.

在中风治疗中越来越多地使用机械血栓切除术为局部动脉内脑内递送治疗剂打开了窗口。在这种情况下，纳米药物的使用可以进一步改善针对特定大脑靶向、跟踪和指导的新疗法的交付。在这项研究中，我们利用这种新的血管内方法来提供具有超顺磁性氧化铁纳米颗粒和 Cy7.5 功能化的生物相容性聚 (DL-乳酸-共-乙醇酸) (PLGA) 纳米胶囊，用于磁靶向、磁共振和荧光分子成像。在接受静脉内或动脉内纳米胶囊的幼稚 (n = 59) 和缺血性 (n = 51) 小鼠中进行完整的生物分布研究，使用两种不同的磁体装置并在 30 分钟至 48 小时内成像，当在控制和缺血条件下使用磁性装置时，显示了动脉内途径用于脑递送的非凡优势，并在皮质靶向方面有特定的改善。在缺血性小鼠 (n = 69) 中评估了安全性，没有显示出全身毒性迹象，也没有增加死亡率、梗塞病变或出血。总之，通过控制血管内给药和磁靶向可以有效和安全地克服治疗性纳米材料的挑战性脑递送，这可以在血管内干预的背景下考虑，以提供多种中风治疗。在缺血性小鼠 (n = 69) 中评估了安全性，没有显示出全身毒性迹象，也没有增加死亡率、梗塞病变或出血。总之，通过控制血管内给药和磁靶向可以有效和安全地克服治疗性纳米材料的挑战性脑递送，这可以在血管内干预的背景下考虑，以提供多种中风治疗。在缺血性小鼠 (n = 69) 中评估了安全性，没有显示出全身毒性迹象，也没有增加死亡率、梗塞病变或出血。总之，通过控制血管内给药和磁靶向可以有效和安全地克服治疗性纳米材料的挑战性脑递送，这可以在血管内干预的背景下考虑，以提供多种中风治疗。