Protein@Cyanine-Based NIR-II Lymphography Enables the Supersensitive Visualization of Lymphedema and Tumor Lymphatic Metastasis,Advanced Healthcare Materials

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Protein@Cyanine-Based NIR-II Lymphography Enables the Supersensitive Visualization of Lymphedema and Tumor Lymphatic Metastasis
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2023-06-02 , DOI: 10.1002/adhm.202301051
Jiajun Xu _{1,

2} , Yijing Du _{1,

2} , Tianyang Han _{1,

2} , Ningning Zhu _{1,

2} , Shoujun Zhu _{1,

2}

Affiliation

Visualization of the lymphatic system is clinically indispensable for the diagnosis and/or treatment of lymphatic diseases. Although indocyanine green (ICG) lymphography becomes an alternate imaging modality compared to traditional lymphoscintigraphy, it is still far from ideal due to the insufficient detection depth and low spatiotemporal resolution. Herein, protein@cyanine probes are rationally developed to solve the limitations of the current near-infrared-I (NIR-I) lymphography. The protein@cyanine probes are synthesized following a chlorine-containing dye-labeling strategy based on structure-selectivity (facile covalent binding between the dye and protein with a 1:1 molar ratio). As expected, the probes display exceptional NIR-II imaging ability with much-improved imaging contrast/resolution and controllable pharmacokinetics, superior to the clinical ICG. The protein@cyanine probes locate lymph nodes and delineate lymphatic vessels with super-high sensitivity and signal-to-background ratio, enabling real-time diagnosing lymphatic diseases such as lymphedema and tumor lymphatic metastasis. In particular, the NIR-II lymphography provides an opportunity to discover the disparate morbidity rate of primary lymphedema in different types of mice. Given the fact of lacking clinically transferable NIR-II probes, this work not only provides a promising strategy for enriching of the current library of NIR-II probes, but also promotes the clinical translation of NIR-II lymphography technology.

中文翻译：

基于 Protein@Cyanine 的 NIR-II 淋巴造影可实现淋巴水肿和肿瘤淋巴转移的超灵敏可视化

淋巴系统的可视化在临床上对于淋巴疾病的诊断和/或治疗是必不可少的。尽管与传统的淋巴闪烁扫描相比，吲哚菁绿（ICG）淋巴造影成为一种替代成像方式，但由于检测深度不足和时空分辨率低，它仍然远非理想。在此，合理开发蛋白质@花青探针来解决当前近红外-I（NIR-I）淋巴成像的局限性。蛋白质@花青探针是按照基于结构选择性（染料和蛋白质之间以 1:1 摩尔比轻松共价结合）的含氯染料标记策略合成的。正如预期的那样，该探针表现出卓越的 NIR-II 成像能力，具有显着改善的成像对比度/分辨率和可控的药代动力学，优于临床 ICG。蛋白@花青探针以超高的灵敏度和信背景比定位淋巴结、勾画淋巴管，能够实时诊断淋巴水肿、肿瘤淋巴转移等淋巴疾病。特别是，NIR-II 淋巴造影提供了发现不同类型小鼠原发性淋巴水肿不同发病率的机会。鉴于缺乏临床可转移的NIR-II探针，这项工作不仅为丰富现有NIR-II探针库提供了有前景的策略，而且促进了NIR-II淋巴成像技术的临床转化。

更新日期：2023-06-02

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