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Lifetime-engineered NIR-II nanoparticles unlock multiplexed in vivo imaging
Nature Nanotechnology ( IF 38.3 ) Pub Date : 2018-08-06 , DOI: 10.1038/s41565-018-0221-0
Yong Fan , Peiyuan Wang , Yiqing Lu , Rui Wang , Lei Zhou , Xianlin Zheng , Xiaomin Li , James A. Piper , Fan Zhang

Deep tissue imaging in the second near-infrared (NIR-II) window holds great promise for physiological studies and biomedical applications1,2,3,4,5,6. However, inhomogeneous signal attenuation in biological matter7,8 hampers the application of multiple-wavelength NIR-II probes to multiplexed imaging. Here, we present lanthanide-doped NIR-II nanoparticles with engineered luminescence lifetimes for in vivo quantitative imaging using time-domain multiplexing. To achieve this, we have devised a systematic approach based on controlled energy relay that creates a tunable lifetime range spanning three orders of magnitude with a single emission band. We consistently resolve selected lifetimes from the NIR-II nanoparticle probes at depths of up to 8 mm in biological tissues, where the signal-to-noise ratio derived from intensity measurements drops below 1.5. We demonstrate that robust lifetime coding is independent of tissue penetration depth, and we apply in vivo multiplexing to identify tumour subtypes in living mice. Our results correlate well with standard ex vivo immunohistochemistry assays, suggesting that luminescence lifetime imaging could be used as a minimally invasive approach for disease diagnosis.



中文翻译:

终身工程化的NIR-II纳米粒子可解锁多重体内成像

在第二个近红外(NIR-II)窗口中的深层组织成像对生理学研究和生物医学应用1,2,3,4,5,6有着广阔的前景。但是,生物物质中的信号衰减不均匀7,8阻碍了多波长NIR-II探针在多路成像中的应用。在这里,我们提出了镧系元素掺杂的NIR-II纳米粒子,具有工程化的发光寿命,可用于使用时域多路复用的体内定量成像。为了实现这一目标,我们设计了一种基于可控能量继电器的系统方法,该方法可在单个发射带上创建跨越三个数量级的可调寿命范围。我们始终如一地从NIR-II纳米粒子探针中解析出在生物组织中最深达8 mm的深度中选择的寿命,在这些组织中,强度测量得出的信噪比降至1.5以下。我们证明了强大的生命周期编码与组织穿透深度无关,并且我们应用了体内多路复用来识别活体小鼠中的肿瘤亚型。

更新日期:2018-12-10
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