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
Translational and Molecular Imaging Institute, Mount Sinai Medical Center, New York, New York, USA.
JACC Cardiovasc Imaging. 2009 May;2(5):637-47. doi: 10.1016/j.jcmg.2008.08.009.
We sought to determine whether gadolinium (Gd)-containing lipid-based nanoparticles (NPs) targeting the macrophage scavenger receptor-B (CD36) improve cardiac magnetic resonance (CMR) detection and characterization of human atherosclerosis.
Gd-containing lipid-based NPs targeting macrophages have improved MR detection of murine atherosclerosis.
Gadolinium-containing untargeted NPs, anti-CD36 NPs, and nonspecific Fc-NPs were created. Macrophages were incubated with fluorescent targeted and nontargeted NPs to determine uptake via confocal microscopy and inductively coupled plasma mass spectroscopy (ICP-MS) quantified Gd uptake. Human aortic specimens were harvested at autopsy. With a 1.5-T scanner, T1, T2, and PDW 3-dimensional scans were performed along with post-contrast scans after 24 h incubation. The T1 and cluster analyses were performed and compared with immunohistopathology.
The NPs had a mean diameter of 125 nm and 14,900 Gd-ions, and relaxivity was 37 mmol/l(-1)s(-1) at 1.5-T and 37 degrees C. Confocal microscopy and ICP-MS demonstrated significant in vitro macrophage uptake of targeted NPs, whereas non-targeted NPs had minimal uptake. On T1 imaging, targeted NPs increased contrast-to-noise ratio (CNR) by 52.5%, which was significantly greater than Fc-NPs (CNR increased 17.2%) and nontargeted NPs (CNR increased 18.7%) (p = 0.001). Confocal fluorescent microscopy showed that NPs target resident macrophages, whereas 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 non-targeted NPs.
Macrophage-specific (CD36) NPs bind human macrophages and improve CMR detection and characterization of human aortic atherosclerosis. Thus, macrophage-specific NPs could help identify high-risk human plaque before the development of an atherothrombotic event.
我们试图确定靶向巨噬细胞清道夫受体-B（CD36）的含钆（Gd）脂质纳米颗粒（NPs）是否能改善心脏磁共振（CMR）对人类动脉粥样硬化的检测和特征分析。
靶向巨噬细胞的含钆脂质纳米颗粒改善了小鼠动脉粥样硬化的磁共振检测。
制备了含钆非靶向纳米颗粒、抗CD36纳米颗粒和非特异性Fc纳米颗粒。将巨噬细胞与荧光靶向和非靶向纳米颗粒孵育，通过共聚焦显微镜确定摄取情况，并通过电感耦合等离子体质谱（ICP-MS）定量钆摄取。在尸检时采集人类主动脉标本。使用1.5-T扫描仪，在孵育24小时后进行T1、T2和质子密度加权（PDW）三维扫描以及对比剂后扫描。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，含有14900个钆离子，在1.5-T和37℃下弛豫率为37 mmol/l⁻¹s⁻¹。共聚焦显微镜和ICP-MS显示靶向纳米颗粒在体外巨噬细胞摄取方面有显著增加，而非靶向纳米颗粒摄取极少。在T1成像上，靶向纳米颗粒使对比噪声比（CNR）增加了52.5%，显著高于Fc纳米颗粒（CNR增加17.2%）和非靶向纳米颗粒（CNR增加18.7%）（p = 0.001）。共聚焦荧光显微镜显示纳米颗粒靶向驻留巨噬细胞，而非靶向纳米颗粒和Fc纳米颗粒在整个斑块中呈弥漫性分布。与非靶向纳米颗粒相比，靶向纳米颗粒在纤维帽中的信号强度增加更大。
巨噬细胞特异性（CD36）纳米颗粒与人巨噬细胞结合，改善了CMR对人类主动脉粥样硬化的检测和特征分析。因此，巨噬细胞特异性纳米颗粒有助于在动脉粥样硬化血栓形成事件发生前识别高危人类斑块。
