Lewis John D, Destito Giuseppe, Zijlstra Andries, Gonzalez Maria J, Quigley James P, Manchester Marianne, Stuhlmann Heidi
Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nat Med. 2006 Mar;12(3):354-60. doi: 10.1038/nm1368. Epub 2006 Feb 26.
A significant impediment to the widespread use of noninvasive in vivo vascular imaging techniques is the current lack of suitable intravital imaging probes. We describe here a new strategy to use viral nanoparticles as a platform for the multivalent display of fluorescent dyes to image tissues deep inside living organisms. The bioavailable cowpea mosaic virus (CPMV) can be fluorescently labeled to high densities with no measurable quenching, resulting in exceptionally bright particles with in vivo dispersion properties that allow high-resolution intravital imaging of vascular endothelium for periods of at least 72 h. We show that CPMV nanoparticles can be used to visualize the vasculature and blood flow in living mouse and chick embryos to a depth of up to 500 microm. Furthermore, we show that the intravital visualization of human fibrosarcoma-mediated tumor angiogenesis using fluorescent CPMV provides a means to identify arterial and venous vessels and to monitor the neovascularization of the tumor microenvironment.
非侵入性体内血管成像技术广泛应用的一个重大障碍是目前缺乏合适的活体成像探针。我们在此描述一种新策略，即利用病毒纳米颗粒作为多价展示荧光染料的平台，以对活生物体内部深处的组织进行成像。可生物利用的豇豆花叶病毒（CPMV）能够以高密度进行荧光标记且无明显淬灭现象，从而产生具有体内分散特性的异常明亮的颗粒，能够对血管内皮进行至少72小时的高分辨率活体成像。我们证明CPMV纳米颗粒可用于可视化活的小鼠和鸡胚胎中的脉管系统和血流，深度可达500微米。此外，我们还证明，使用荧光CPMV对人纤维肉瘤介导的肿瘤血管生成进行活体可视化，为识别动脉和静脉血管以及监测肿瘤微环境的新生血管形成提供了一种方法。
