A Nanoprobe for Diagnosing and Mapping Lymphatic Metastasis of Tumor Using 3D Multispectral Optoacoustic Tomography Owing to Aggregation/Deaggregation Induced Spectral Change
A Nanoprobe for Diagnosing and Mapping Lymphatic Metastasis of Tumor Using 3D Multispectral Optoacoustic Tomography Owing to Aggregation/Deaggregation Induced Spectral Change
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DOI：
10.1002/adfm.201807960
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发表时间：
2019-01
影响因子：
19
通讯作者：
Yinglong Wu;Junjie Chen;Lihe Sun;Fang Zeng;Shuizhu Wu
中科院分区：
文献类型：
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作者：
Yinglong Wu;Junjie Chen;Lihe Sun;Fang Zeng;Shuizhu Wu
肿瘤淋巴转移是癌症相关死亡的主要原因之一，诊断淋巴转移对优化疾病管理和患者预后具有重要意义。本文报道了一种开启光声纳米探针用于体内淋巴转移的无创诊断和定位。设计并合成了一种带正电的高消光系数的含三氰呋喃多烯发色团（TCHM），并使其与带负电的透明质酸形成纳米探针。tchm在纳米探针内呈聚集状态，在882 nm处表现出微弱的吸收，癌细胞中过表达的透明质酸酶特异性地将透明质酸降解成小片段并分解tchm，从而大大增强了882 nm处的吸收并产生突出的光声信号。对于体内多光谱光声断层扫描（MSOT）成像，首先对小鼠皮下肿瘤和原位膀胱肿瘤模型进行成像，以证明纳米探针检测HAase过表达肿瘤的能力。建立小鼠肿瘤淋巴转移模型，成功实现了肿瘤淋巴转移的光声成像和跟踪。成像结果通过多种生化分析进行验证。此外，还获得了三维MSOT效果图，可以在时空上精确定位和跟踪肿瘤在淋巴系统中的转移。
Lymphatic metastasis of tumor is one of leading causes of cancer‐related death, and diagnosing lymphatic metastasis is of significance in terms of optimal disease management and possible better outcomes for patients. Herein a turn‐on optoacoustic nanoprobe is reported for noninvasively diagnosing and locating lymphatic metastasis in vivo. A positively charged tricyanofuran‐containing polyene chromophore (TCHM) with high extinction coefficient is designed, synthesized, and allowed to form the nanoprobe with a negatively charged hyaluronan. The TCHMs take an aggregated state within the nanoprobe and exhibit weak absorption at 882 nm, the overexpressed hyaluronidase in cancer cells specifically degrades hyaluronan into small fragments and disaggregates TCHMs, thereby greatly enhancing the absorption at 882 nm and generating prominent optoacoustic signals. For multispectral optoacoustic tomography (MSOT) imaging in vivo, mice models with subcutaneous tumor and orthotopic bladder tumor are imaged first to demonstrate the nanoprobe's capability for detecting HAase‐overexpressing tumors. A mouse model of lymphatic metastasis of tumor is then established and the lymphatic metastasis is successfully imaged and tracked optoacoustically. The imaging results were verified using multiple biochemical assays. Moreover, 3D MSOT renderings are obtained for precisely locating and tracking the metastasis of tumor in lymphatic system in a spatiotemporal manner.