Family of enhanced photoacoustic imaging agents for high-sensitivity and multiplexing studies in living mice.-猫眼课题宝

用于活体小鼠高灵敏度和多重研究的增强型光声成像剂系列。

DOI：

10.1021/nn204352r

发表时间：

2012-06-26

期刊：

ACS nano

影响因子：

17.1

通讯作者：

中科院分区：

材料科学1区

文献类型：

作者：

de la Zerda A;Bodapati S;Teed R;May SY;Tabakman SM;Liu Z;Khuri-Yakub BT;Chen X;Dai H;Gambhir SS

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397693/?report=classic

光声成像是一种独特的成像方式，它在很大程度上克服了光学成像的分辨率和深度限制，同时保持相对高的对比度。然而，由于许多疾病不会表现出内源性光声造影，因此开发能够靶向患病组织的外源性光声造影剂是必要的。在这里，我们提出了一个家庭的新的光声造影剂，是基于小的光学染料的单壁碳纳米管（SWNT染料）的结合。我们使用不同的光学染料合成了五种不同的SWNT-染料造影剂，创造了五种“口味”的SWNT-染料纳米颗粒。特别地，与普通SWNT相比，用QSY 21（SWNT-QSY）或吲哚菁绿色（SWNT-ICG）涂覆的SWNT在活体动物中表现出超过100倍的光声对比度，导致亚纳摩尔灵敏度。然后，我们将SWNT-染料缀合物与环Arg-Gly-Asp（RGD）肽缀合，以分子靶向与肿瘤血管生成相关的αvβ3整联蛋白。静脉注射这些肿瘤靶向显像剂给荷瘤小鼠显示，肿瘤中的光声信号显著高于注射非靶向造影剂的小鼠。最后，我们能够在同一位置皮下注射两种颗粒的活动物中光谱分离SWNT-QSY和SWNT-ICG的光声信号，从而为体内研究的多路复用提供了可能性。

Photoacoustic imaging is a unique modality that overcomes to a great extent the resolution and depth limitations of optical imaging while maintaining relatively high-contrast. However, since many diseases will not manifest an endogenous photoacoustic contrast, it is essential to develop exogenous photoacoustic contrast agents that can target diseased tissue(s). Here we present a family of novel photoacoustic contrast agents that are based on the binding of small optical dyes to single walled carbon nanotubes (SWNT-dye). We synthesized five different SWNT-dye contrast agents using different optical dyes, creating five “flavors” of SWNT-dye nanoparticles. In particular, SWNT that were coated with either QSY21 (SWNT-QSY) or Indocyanine Green (SWNT-ICG) exhibited over 100-times higher photoacoustic contrast in living animals compared to plain SWNTs, leading to subnanomolar sensitivities. We then conjugated the SWNT-dye conjugates with cyclic Arg-Gly-Asp (RGD) peptides to molecularly target the αvβ3 integrin, which is associated with tumor angiogenesis. Intravenous administration of these tumor-targeted imaging agents to tumor-bearing mice showed significantly higher photoacoustic signal in the tumor than in mice injected with the untargeted contrast agent. Finally, we were able to spectrally separate the photoacoustic signals of SWNT-QSY and SWNT-ICG in living animals injected subcutaneously with both particles in the same location, opening the possibility for multiplexing in vivo studies.