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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\u2010infrared\u2010I (NIR\u2010I) lymphography. The protein@cyanine probes are synthesized following a chlorine\u2010containing dye\u2010labeling strategy based on structure\u2010selectivity (facile covalent binding between the dye and protein with a 1:1 molar ratio). As expected, the probes display exceptional NIR\u2010II imaging ability with much\u2010improved imaging contrast\/resolution and controllable pharmacokinetics, superior to the clinical ICG. The protein@cyanine probes locate lymph nodes and delineate lymphatic vessels with super\u2010high sensitivity and signal\u2010to\u2010background ratio, enabling real\u2010time diagnosing lymphatic diseases such as lymphedema and tumor lymphatic metastasis. In particular, the NIR\u2010II 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\u2010II probes, this work not only provides a promising strategy for enriching of the current library of NIR\u2010II probes, but also promotes the clinical translation of NIR\u2010II lymphography technology.<\/jats:p>","DOI":"10.1002\/adhm.202301051","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T09:57:01Z","timestamp":1685699821000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Protein@Cyanine\u2010Based NIR\u2010II Lymphography Enables the Supersensitive Visualization of Lymphedema and Tumor Lymphatic Metastasis"],"prefix":"10.1002","volume":"12","author":[{"given":"Jiajun","family":"Xu","sequence":"first","affiliation":[{"name":"Joint Laboratory of Opto\u2010Functional Theranostics in Medicine and Chemistry First Hospital of Jilin University  Changchun 130021 P. R. 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