血小板膜磁性纳米载体作为MR影像传感器用于缺血性脑卒中血管损伤网络的描绘及靶向预保护

Platelet magnetic nanocarriers as MRI sensors to delineate vascular injury network and targeted pre-protection in ischemic stroke

缺血性脑卒中病灶的准确定位和受损血管网络的描绘是制定与实施有效治疗策略的关键.在本研究中,我们基于血小板膜,开发了装载L-精氨酸和γ-Fe_(2)O_(3)磁性纳米颗粒的仿生纳米载体(PAMNs),并实现了包括T_(2)^(*)加权成像(T_(2)^(*)WI)和弥散加权成像(DWI)的多参数磁共振成像(MRI)下急性缺血性脑卒中血管网络受损严重程度的评估.结果表明,PAMNs可特异性靶向不同类型的受损血管,并且随着PAMNs在病灶区域的累积,T_(2)^(*)加权成像可有效描绘出受损区域的血管损伤网络,尤其可以区分梗死核心与半暗带.此外,PAMNs中L-精氨酸的释放可诱导闭塞血管扩张,因此,我们进一步利用弥散加权成像来评估其预保护作用,发现PAMNs可有效抑制缺血病灶的扩大.因此,基于PAMNs的靶向与MRI影像增强功能,可实现缺血性脑卒中早期病灶的靶向定位、血管网络受损严重程度评估、实时监测和预保护,在缺血性脑卒中诊疗中具有巨大的应用潜力.

Accurate mapping the damaged vascular network is key to subsquent effective therapeutic strategy implementation in ischemic stroke.In this study,magnetic resonance imaging(MRI)based on a platelet membrane biomimetic magnetic nanocarrier,loaded with L-arginine andγ-Fe_(2)O_(3)magnetic nanoparticles(PAMNs),has been developed for delineating the vascular injury network in acute ischemic stroke.Due to the loading ofγ-Fe_(2)O_(3)nanoparticles,multi-parameter MRI including T_(2)^(*)-weighted imaging(T_(2)^(*)WI)and diffusion-weighted imaging(DWI)have been used to localize the stroke lesion and evaluate the severity of damaged vasuclar network,respectively.Results demonstrated that the PAMNs can specifically target to different types of damaged blood vasculature.Based on the PAMNs accumulation in the stroke lesion,T_(2)^(*)imaging delineated the damaged vascular injury network,espcially for penumbra.Furthermore,with the L-arginine release in the lesion,the DWI of MRI was applied to evaluate the pre-protection effect.This showed great potential for accurate positioning and real-time monitoring of stroke ischemic lesions.Therefore,the PAMNs-based MRI technique is feasible for vascular obstruction/thrombus location,severity assessment,and real-time monitoring of lesion development in ischemic lesions in the early stage of stroke.