Dual-targeting Theranostic System with Mimicking Apoptosis to Promote Myocardial Infarction Repair via Modulation of Macrophages.
Dual-targeting Theranostic System with Mimicking Apoptosis to Promote Myocardial Infarction Repair via Modulation of Macrophages.
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模拟细胞凋亡的双靶点治疗诊断系统通过调节巨噬细胞促进心肌梗死修复
DOI：
10.7150/thno.21040
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发表时间：
2017
期刊：
影响因子：
12.4
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Chen J;Yang J;Liu R;Qiao C;Lu Z;Shi Y;Fan Z;Zhang Z;Zhang X
目前心肌梗死（MI）的治疗效果不理想，主要是由于炎症反应不受控制和早期诊断延迟。针对这些问题，首先，磷脂酰丝氨酸（PS）通过与巨噬细胞表面的PS受体（PSR）结合来调节巨噬细胞（MΦ）的表型，并解决早期炎症。其次，采用高灵敏度的磁性氧化铁纳米立方体（MION），通过磁共振成像（MRI）实现早期可视化。然而，MION作为造影剂的主要缺点是其疏水性和递送不足。因此，两性离子可生物降解共聚物聚（丙交酯）-聚羧基甜菜碱（PLA-PCB，PP），伴随着PS，用于提供一个良好的胶体稳定性和长的血液循环的纳米立方体。鉴于上述情况，构建了治疗诊断纳米系统（PP/PS@ MION）用于MI的早期治疗。通过外磁场诱导靶向和PS靶向，纳米系统增强了梗死区的积聚，并加速了早期炎症反应的消退。此外，系统中的纳米立方体通过PCB的质子化促进从内体/溶酶体逃逸，这有助于准确的MRI。该纳米系统在MI模型大鼠中表现出良好的抗炎作用和成像能力。因此，这种治疗诊断纳米系统可以实现准确的可视化，并显著提高MI早期的治疗效果。
Currently unsatisfactory treatment of myocardial infarction (MI) is due to the unbridled inflammation and the delayed diagnosis at the early stage. To address these problems, firstly, phosphatidylserine (PS) was used to modulate the phenotypes of macrophages (MΦ) and resolve the early inflammation via binding to PS receptors (PSR) on macrophage surface. Secondly, highly-sensitive magnetic iron oxide nanocubes (MIONs) were adopted to realize the early visualization via magnetic resonance imaging (MRI). However, the major drawback for MIONs as contrast agents was their hydrophobic properties and insufficient delivery. Hence, zwitterionic biodegradable copolymer poly(lactide)-polycarboxybetaine (PLA-PCB, PP), companied with PS, was used to provide a good colloidal stability and long blood circulation for the nanocubes. Given the above, a theranostic nanosystem (PP/PS@MIONs) was constructed for early treatment of MI. With external magnetic field-induced targeting and PS targeting, the nanosystem enhanced the accumulation in infarcted area, and accelerated the resolution of early inflammatory responses. Moreover, the nanocubes in system were promoted to escape from endosomes/lysosomes via protonation of PCB, which contributes to accurate MRI. This nanosystem showed good inflammation-resolving effects and imaging ability in MI model rats. Therefore, this theranostic nanosystem can realize accurate visualization and significantly improve the treatment efficacy of MI at early stage.
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影响因子：
2.6
作者：
Finn, J. P.;Nguyen, K. -L.;Han, F.;Zhou, Z.;Salusky, I.;Ayad, I.;Hu, P.
通讯作者：
Hu, P.
影响因子：
3.5
作者：
Florian, Anca;Ludwig, Anna;Yilmaz, Ali
通讯作者：
Yilmaz, Ali
DOI：
10.2353/ajpath.2010.090759
发表时间：
2010-05
期刊：
The American journal of pathology
影响因子：
--
作者：
Dobaczewski M;Xia Y;Bujak M;Gonzalez-Quesada C;Frangogiannis NG
通讯作者：
Frangogiannis NG
影响因子：
7.5
作者：
Alam, Shirjel R.;Shah, Anoop S. V.;Semple, Scott I. K.
通讯作者：
Semple, Scott I. K.
影响因子：
4.6
作者：
Kleinbongard, Petra;Schulz, Rainer;Heusch, Gerd
通讯作者：
Heusch, Gerd