An Activatable Near-Infrared Chromophore for Multispectral Optoacoustic Imaging of Tumor Hypoxia and for Tumor Inhibition
An Activatable Near-Infrared Chromophore for Multispectral Optoacoustic Imaging of Tumor Hypoxia and for Tumor Inhibition
复制标题
用于肿瘤缺氧多光谱光声成像和肿瘤抑制的可激活近红外发色团
DOI：
10.7150/thno.36755
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发表时间：
2019-01-01
期刊：
影响因子：
12.4
通讯作者：
Wu, Shuizhu
中科院分区：
文献类型：
--
作者：
Huang, Jing;Wu, Yinglong;Wu, Shuizhu
缺氧是实体瘤的关键标志，肿瘤缺氧通常导致肿瘤进展、治疗抵抗和预后不良。准确、高空间分辨率地检测和成像肿瘤缺氧有助于制定优化的治疗方案，从而获得更好的患者预后。方法：肿瘤缺氧可裂解偶氮连接体，释放近红外荧光团（NR-NH2），同时释放活性药物。NR-NH2在约680 nm处表现出强吸收带，在710 nm处表现出强荧光带，可用于荷瘤小鼠模型的多光谱光声断层成像（MSOT）和肿瘤缺氧荧光成像。结果：脂质体包被可活化的发色团（nr -偶氮）用于检测/成像肿瘤缺氧和肿瘤抑制。在这个发色团中，一个基于杂蒽的近红外荧光团作为光声和荧光报告分子，一个偶氮连接体作为缺氧反应部分，一个氮芥作为治疗药物。nr -偶氮在约575 nm处有吸收，但由于存在强吸电子偶氮连接剂，其荧光可以忽略不计。结论：我们展示了一种光声和荧光系统，不仅可以在体内成像肿瘤缺氧，而且可以实现肿瘤抑制。
Hypoxia is a key hallmark of solid tumors and tumor hypoxia usually contributes to cancer progression, therapeutic resistance and poor outcome. Accurately detecting and imaging tumor hypoxia with high spatial resolution would be conducive to formulating optimized treatment plan and thus achieving better patient outcome. Methods: Tumor hypoxia can cleave the azo linker and release a NIR fluorophore (NR-NH2) and release the active drug as well. NR-NH2 shows a strong absorption band at around 680 nm and a strong fluorescence band at 710 nm, allowing for both multispectral optoacoustic tomography imaging (MSOT) and fluorescent imaging of tumor hypoxia in a tumor-bearing mouse model. Results: Liposome encapsulated with the activatable chromophore (NR-azo) for detecting/imaging tumor hypoxia and for tumor inhibition was demonstrated. For this chromophore, a xanthene-based NIR fluorophore acts as the optoacoustic and fluorescent reporter, an azo linker serves as the hypoxia-responsive moiety and a nitrogen mustard as the therapeutic drug. NR-azo shows an absorption at around 575 nm but exhibits negligible fluorescence due to the existence of the strong electron-withdrawing azo linker. Conclusion: We demonstrated an optoacoustic and fluorescent system for not only imaging tumor hypoxia in vivo but also achieving tumor inhibition.