NIR-II cell endocytosis-activated fluorescent probes for in vivo high-contrast bioimaging diagnostics.
NIR-II cell endocytosis-activated fluorescent probes for in vivo high-contrast bioimaging diagnostics.
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DOI：
10.1039/d1sc02763h
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发表时间：
2021-08-11
期刊：
影响因子：
8.4
通讯作者：
Zhang F
中科院分区：
文献类型：
--
作者：
He Y;Wang S;Yu P;Yan K;Ming J;Yao C;He Z;El-Toni AM;Khan A;Zhu X;Sun C;Lei Z;Zhang F
荧光探针在生物成像、精准临床诊断和手术方面具有巨大潜力。然而，由于血液和正常组织中的组织散射和非特异性激活的大量背景干扰，当前的探针仅限于体内高对比度诊断。在这里，我们开发了一种细胞内吞激活荧光（CEAF）探针，它由亲水性聚合物单元和酸性pH敏感的小分子荧光部分组成，在“组织透明”的第二近红外（NIR-II）窗口中工作。 CEAF探针在水和血液中以猝灭的纳米聚集体的形式稳定存在，并且在解聚和质子化的协同机制驱动下，可以通过细胞内吞作用选择性地激活并保留在溶酶体中。分别使用被动靶向和亲和标记的 CEAF 探针对肿瘤和炎症进行体内成像，产生目标与背景比率超过 15 的高度特异性信号，并将观察时间延长至 35 小时，从而对外科、诊断和基础生物医学研究产生积极影响。由解聚和质子化触发的细胞内吞激活荧光 (CEAF) 探针设计用于第二近红外窗口 (1000–1700 nm) 的高对比度体内生物成像和诊断。
Fluorescence probes have great potential to empower bioimaging, precision clinical diagnostics and surgery. However, current probes are limited to in vivo high-contrast diagnostics, due to the substantial background interference from tissue scattering and nonspecific activation in blood and normal tissues. Here, we developed a kind of cell endocytosis-activated fluorescence (CEAF) probe, which consists of a hydrophilic polymer unit and an acid pH-sensitive small-molecule fluorescent moiety that operates in the “tissue-transparent” second near-infrared (NIR-II) window. The CEAF probe stably presents in the form of quenched nanoaggregates in water and blood, and can be selectively activated and retained in lysosomes through cell endocytosis, driven by a synergetic mechanism of disaggregation and protonation. In vivo imaging of tumor and inflammation with a passive-targeting and affinity-tagged CEAF probe, respectively, yields highly specific signals with target-to-background ratios over 15 and prolonged observation time up to 35 hours, enabling positive implications for surgical, diagnostic and fundamental biomedical studies. A Cell Endocytosis-Activated Fluorescent (CEAF) probe triggered by disaggregation and protonation is designed for high contrast in vivo bioimaging and diagnostics in the second near-infrared window (1000–1700 nm).
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