Macrophage-specific lipid-based nanoparticles improve cardiac magnetic resonance detection and characterization of human atherosclerosis.
Macrophage-specific lipid-based nanoparticles improve cardiac magnetic resonance detection and characterization of human atherosclerosis.
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DOI：
10.1016/j.jcmg.2008.08.009
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发表时间：
2009-05
影响因子：
14
通讯作者：
Fayad, Zahi A.
中科院分区：
文献类型：
--
作者：
Lipinski, Michael J.;Frias, Juan C.;Amirbekian, Vardan;Briley-Saebo, Karen C.;Mani, Venkatesh;Samber, Daniel;Abbate, Antonio;Aguinaldo, Juan Gilberto S.;Massey, Davis;Fuster, Valentin;Vetrovec, George W.;Fayad, Zahi A.
我们试图确定靶向巨噬细胞清道夫受体-B（CD 36）的含钆（Gd）的脂质纳米颗粒（NP）是否能改善人类动脉粥样硬化的磁共振（MR）检测和表征。使用靶向巨噬细胞的基于钆Gd的脂质的NP的MR成像检测动脉粥样硬化的能力可以在动脉粥样硬化血栓形成事件之前早期检测高风险病变。靶向巨噬细胞的含Gd脂质纳米粒改善了鼠动脉粥样硬化的MR检测。产生了含Gd的NP、抗CD 36 NP和Fc-NP。将巨噬细胞与荧光靶向和非靶向NP孵育，以通过共聚焦显微镜和电感耦合等离子体质谱（ICP-MS）定量Gd摄取来确定摄取。尸检时采集人主动脉标本。使用1.5 T扫描仪，在孵育24 h后进行T1、T2和PDW三维扫描沿着造影后扫描。进行T1和聚类分析，并与免疫组织病理学进行比较。纳米颗粒的平均直径为125 nm，14，900个Gd离子，在1.5T和37°C下的弛豫率为37 mM-1 s-1。共聚焦显微镜和ICP-MS显示靶向NP的体外巨噬细胞摄取显著，而非靶向NP的摄取最小。在T1成像上，靶向NPs使CNR增加52.5%，这显著大于Fc-NPs（CNR增加17.2%）和非靶向NPs（CNR增加18.7%）（p=0.001）。共聚焦荧光显微镜显示NP靶向驻留的巨噬细胞，而非靶向的NP和Fc-NP在整个斑块中弥漫存在。靶向的NP在纤维帽中具有更大的信号强度增加（p<0.001），而非靶向的NP和Fc-NP在脂质核心中具有更大的增加（p<0.01）。巨噬细胞特异性（CD 36）NPs结合人巨噬细胞并改善人主动脉粥样硬化的MR检测和表征。因此，巨噬细胞特异性纳米颗粒可以帮助识别高风险的人类斑块之前，动脉粥样硬化血栓事件的发展。
We sought to determine if gadolinium (Gd)-containing lipid-based nanoparticles (NPs) targeting the macrophage scavenger receptor-B (CD36) improve magnetic resonance (MR) detection and characterization of human atherosclerosis. The ability to detect atherosclerosis with MR imaging using gadolinium Gd-containing lipid-based NPs targeting macrophages may enable early detection of high-risk lesions prior to an atherothrombotic event. Gd-containing lipid-based NPs targeting macrophages improved MR detection of murine atherosclerosis. Gd-containing NPs, anti-CD36 NPs and Fc-NPs were created. Macrophages were incubated with fluorescent targeted and non-targeted NPs to determine uptake via confocal microscopy and inductively coupled plasma mass spectroscopy (ICP-MS) quatified Gd uptake. Human aortic specimens were harvested at autopsy. Using a 1.5 T scanner, T1, T2, and PDW 3-dimensional scans were performed along with post-contrast scans after 24 h incubation. T1 and cluster analysis were performed and compared with immunohistopathology. The NPs had a mean diameter of 125 nm, 14,900 Gd-ions, and relaxivity was 37 mM-1s-1 at 1.5T and 37°C. Confocal microscopy and ICP-MS demonstrated significant in vitro macrophage uptake of targeted NPs while non-targeted NPs had minimal uptake. On T1 imaging, targeted NPs increased CNR by 52.5% which was significantly great than Fc-NPs (CNR increased 17.2%) and non-targeted NPs (CNR increased 18.7%) (p=0.001). Confocal fluorescent microscopy showed that NPs target resident macrophages while the untargeted NPs and Fc-NPs are found diffusely throughout the plaque. Targeted NPs had a greater signal intensity increase in the fibrous cap compared with (p<0.001) while non-targeted NPs and Fc-NPs had a greater increase in the lipid core (p<0.01). Macrophage-specific (CD36) NPs bind human macrophages and improved MR detection and characterization of human aortic atherosclerosis. Thus, macrophage-specific NPs could help identify high-risk human plaque prior to the development of an atherothrombotic event.
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DOI：
10.1007/bf00981886
发表时间：
1995-01-01
期刊：
Methods in Cell Science
影响因子：
--
作者：
Bannon, Paul G.;Dean, Roger T.;Dawes, Joan
通讯作者：
Dawes, Joan
影响因子：
37.8
作者：
TOPOL, EJ;NISSEN, SE
通讯作者：
NISSEN, SE
影响因子：
15.9
作者：
Febbraio, M;Podrez, EA;Silverstein, RL
通讯作者：
Silverstein, RL
影响因子：
5.3
作者：
Guy, Ella;Kuchibhotla, Sai;Febbraio, Maria
通讯作者：
Febbraio, Maria
DOI：
10.1016/0735-1097(88)90356-7
发表时间：
1988-07-01
影响因子：
24
作者：
AMBROSE, JA;TANNENBAUM, MA;FUSTER, V
通讯作者：
FUSTER, V