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Although molecular imaging shows the potential for non\u2010intrusively interrogating kidney disease\u2010related biomarkers, the limited kidney contrast of many fluorophores, owing to their relatively low distribution in the kidney, hinders their effectiveness for kidney disease detection. Herein, for the first time, an amino\u2010functionalization strategy is proposed to construct a library of kidney\u2010targeting fluorophores NHcy with tunable emissions from NIR\u2010I to NIR\u2010II. Among these, NHcy\u20108 is the first small\u2010molecule NIR\u2010II dye without a renal clearance moiety, designed specifically for kidney\u2010targeting imaging. Building on this class of NIR\u2010II fluorophore, the first NIR\u2010II small\u2010molecule kidney\u2010targeting pH probe NIR\u2010II\u2010pH is developed, which exhibits a desirable kidney distribution after intravenous injection and is fluorescent only after activation by acidosis. NIR\u2010II in vivo fluorescence\/photoacoustic imaging of kidney disease models induced by cisplatin and renal I\/R injury using NIR\u2010II\u2010pH reveals increasingly severe metabolic acidosis as the disease progressed, enabling sensitive detection of the onset of acidosis 36\u00a0h (cisplatin group) earlier than clinical methods. Thus, this study introduces a practical NIR\u2010II kidney\u2010targeting probe and provides a useful molecular blueprint for guiding kidney\u2010targeting NIR\u2010II fluorophores as diagnostic aids for kidney diseases.<\/jats:p>","DOI":"10.1002\/adhm.202402828","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T02:05:43Z","timestamp":1728353143000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Engineering of Kidney\u2010Targeting Fluorophores with Tunable Emission from NIR\u2010I to NIR\u2010II for Early Diagnosis of Kidney Disease"],"prefix":"10.1002","volume":"13","author":[{"given":"Yulan","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences Guangxi Normal University  Guilin 541004 P. 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