Xu Li, Li Zhe, Ma Yuan, Lei Lingling, Yue Renye, Cao Hui, Huan Shuangyan, Sun Wei, Song Guosheng
State Key Laboratory for Chemo/ Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, Engineering, Hunan University, Changsha 410082, China.
Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing, Medical University.
Research (Wash D C). 2023 Jul 19;6:0186. doi: 10.34133/research.0186. eCollection 2023.
The majority of atherothrombotic events (e.g., cerebral or myocardial infarction) often occur as a result of plaque rupture or erosion in the carotid, and thereby it is urgent to assess plaque vulnerability and predict adverse cerebrovascular events. However, the monitoring evolution from stable plaque into life-threatening high-risk plaque in the slender carotid artery is a great challenge, due to not enough spatial resolution for imaging the carotid artery based on most of reported fluorescent probes. Herein, copolymerizing with the small molecules of acceptor-donor-acceptor-donor-acceptor (A-D-A'-D-A) and the electron-donating units (D'), the screened second near-infrared (NIR-II) nanoprobe presents high quantum yield and good stability, so that it enables to image slender carotid vessel with enough spatial resolution. Encouragingly, NIR-II nanoprobe can effectively target to intraplaque macrophage, meanwhile distinguishing vulnerable plaque in carotid atherosclerosis in living mice. Moreover, the NIR-II nanoprobe can dynamically monitor the fresh bleeding spots in carotid plaque, indicating the increased risk of plaque instability. Besides, magnetic resonance imaging is integrated with NIR-II fluorescence imaging to provide contrast for subtle structure (e.g., narrow lumen and lipid pool), via incorporating ultrasmall superparamagnetic iron oxide into the NIR-II nanoprobe. Thus, such hybrid NIR-II/magnetic resonance imaging multimodal nanoprobe provides an effective tool for assessing carotid plaque burden, selecting high-risk plaque, and imaging intraplaque hemorrhage, which is promising for reducing cerebral/ myocardial infarction-associated morbidity and mortality.
大多数动脉粥样硬化血栓形成事件(如脑梗死或心肌梗死)通常是由于颈动脉斑块破裂或糜烂所致,因此评估斑块易损性并预测不良脑血管事件迫在眉睫。然而,由于基于大多数已报道的荧光探针,对颈动脉成像的空间分辨率不足,监测细长颈动脉中稳定斑块向危及生命的高危斑块的演变是一项巨大挑战。在此,通过与受体-供体-受体-供体-受体(A-D-A'-D-A)小分子和供电子单元(D')共聚,筛选出的第二代近红外(NIR-II)纳米探针具有高量子产率和良好的稳定性,从而能够以足够的空间分辨率对细长的颈动脉血管进行成像。令人鼓舞的是,NIR-II纳米探针能够有效靶向斑块内巨噬细胞,同时区分活体小鼠颈动脉粥样硬化中的易损斑块。此外,NIR-II纳米探针能够动态监测颈动脉斑块中的新鲜出血点,表明斑块不稳定风险增加。此外,通过将超小超顺磁性氧化铁掺入NIR-II纳米探针中,将磁共振成像与NIR-II荧光成像相结合,为细微结构(如狭窄管腔和脂质池)提供对比。因此,这种NIR-II/磁共振成像多模态纳米探针为评估颈动脉斑块负荷、选择高危斑块以及对斑块内出血进行成像提供了一种有效工具,有望降低脑梗死/心肌梗死相关的发病率和死亡率。