SR-A-Targeted Phase Transition Nanoparticles for the Detection and Treatment of Atherosclerotic Vulnerable Plaques
SR-A-Targeted Phase Transition Nanoparticles for the Detection and Treatment of Atherosclerotic Vulnerable Plaques
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用于检测和治疗动脉粥样硬化易损斑块的 SR-A 靶向相变纳米颗粒
DOI：
10.1021/acsami.8b18190
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发表时间：
2019
影响因子：
9.5
通讯作者：
Dajing Guo
中科院分区：
文献类型：
--
作者：
Man Ye;Jun Zhou;Yixin Zhong;Jie Xu;Jingxin Hou;Xingyue Wang;Zhigang Wang;Dajing Guo
动脉粥样硬化是猝死和心肌梗死的主要原因，由不稳定斑块引起。因此，早期发现不稳定斑块并进行相应的治疗，可改善预后，降低死亡率。在这项研究中，我们描述了一种方案，用于制备纳米颗粒（NP）相转变材料全氟己烷（PFH）和硫酸葡聚糖（DS）靶向A类清道夫受体（SR-A）的诊断和治疗动脉粥样硬化易损斑块。结果表明，成功制备了Fe-PFH-聚乳酸-羟基乙酸共聚物（PLGA）/壳聚糖（CS）-DS纳米粒，该纳米粒在低强度聚焦超声（LIFU）照射下能够发生相变，实现超声成像;高载流率的Fe 3 O 4对磁共振成像（MRI）具有良好的负增强效果。NPs对活化的巨噬细胞具有高的结合亲和力，并且可以被巨噬细胞内吞，并且在体外通过声滴蒸发（ADV）效应在LIFU照射下显著诱导细胞凋亡。此外，在高胆固醇诱导的载脂蛋白E（ApoE）敲除（KO）（apoE -/-）小鼠的离体动脉粥样硬化斑块模型中，NPs选择性地积聚在主动脉区域活化的巨噬细胞上表达的SR-A位点。这一结果也通过体内MRI证实，其中NP可以靶向主动脉斑块并降低T2* 信号。在体内，LIFU诱导的相变可导致斑块上巨噬细胞凋亡。综上所述，Fe-PFH-PLGA/CS-DS纳米粒可用作多模式和多功能探针，并有望实现易损斑块的特异性诊断和靶向治疗。
Atherosclerosis is a major cause of sudden death and myocardial infarction, instigated by unstable plaques. Thus, the early detection of unstable plaques and corresponding treatment can improve the prognosis and reduce mortality. In this study, we describe a protocol for the preparation of nanoparticles (NPs) combined with the phase transitional material perfluorohexane (PFH) and with dextran sulfate (DS) targeting class A scavenger receptors (SR-A) for the diagnosis and treatment of atherosclerotic vulnerable plaques. The results showed that the Fe-PFH-poly (lactic-co-glycolic acid) (PLGA)/chitosan (CS)-DS NPs were fabricated successfully, with the ability to undergo phase transition by low intensity focused ultrasound (LIFU) irradiation to achieve ultrasound (US) imaging; a high carrier rate of Fe3O4 had a good negative enhancement effect on magnetic resonance imaging (MRI). The NPs had a high binding affinity for activated macrophages and could be endocytosed by the macrophages and notably induced apoptosis under LIFU irradiation by an acoustic droplet vaporization (ADV) effect in vitro. Furthermore, in an ex vivo atherosclerotic plaque model of apolipoprotein E (ApoE) knockout (KO) (apoE -/-) mice induced by high cholesterol, the NPs selectively accumulated at the sites of SR-A expressed on the activated macrophages of the aortic region. This result was also confirmed by MRI in vivo, where the NPs could be targeted to the aortic plaque and reduced the T2* signal. The LIFU-induced phase transition could lead to the apoptosis of macrophages on plaques in vivo. In summary, Fe-PFH-PLGA/CS-DS NPs may be applied as multimodal and multifunctional probes and are expected to enable the specific diagnosis and targeted therapy of vulnerable plaques.