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Given the complementary advantages of fluorescence (FL) and photoacoustic (PA) imaging, there is a growing demand for dual\u2010ratiometric probes that enable precise in vivo monitoring of H<jats:sub>2<\/jats:sub>S levels. In this study, the use of 2\u2010mercapto\u20101,3,4\u2010thiadiazole (MTD) as a novel recognition group of H<jats:sub>2<\/jats:sub>S is presented for the first time, following conjugation with cyanine dyes to obtain a new PA probe Cy\u2010MTD. To achieve dual\u2010ratiometric imaging, Cy\u2010MTD is incorporated into down\u2010conversion nanoparticle (DCNP), resulting in the creation of a pioneering NIR\u2010II FL\/NIR\u2010I PA dual\u2010ratiometric nanoprobe DCNP@Cy\u2010MTD. Cy\u2010MTD undergoes the blueshift in absorption from 840 to 670\u00a0nm after reaction with H<jats:sub>2<\/jats:sub>S, enabling NIR\u2010I ratiometric PA imaging of H<jats:sub>2<\/jats:sub>S by measuring the ratio of PA signal at 670 and 840\u00a0nm (PA<jats:sub>670<\/jats:sub>\/PA<jats:sub>840<\/jats:sub>). In addition, due to the strong absorption of Cy\u2010MTD \u2248840\u00a0nm and the overlapping between the absorption spectrum of Cy\u2010MTD and 808\u00a0nm excitation band of DCNP, the 808 nm\u2010excited FL emission (F<jats:sub>1550<\/jats:sub>\u00a0<jats:sub>nm,808Ex<\/jats:sub>) of DCNP in DCNP@Cy\u2010MTD nanoprobe is quenched through the competitive absorption, while it is restored upon the interaction with H<jats:sub>2<\/jats:sub>S because of the blueshift in absorption of Cy\u2010MTD. Using the stable FL emission of DCNP under 980\u00a0nm excitation (F<jats:sub>1550<\/jats:sub>\u00a0<jats:sub>nm,980Ex<\/jats:sub>) as the reference signal, NIR\u2010II ratiometric FL imaging (F<jats:sub>1550<\/jats:sub>\u00a0<jats:sub>nm,808Ex<\/jats:sub>\/F<jats:sub>1550<\/jats:sub>\u00a0<jats:sub>nm,980Ex<\/jats:sub>) of H<jats:sub>2<\/jats:sub>S is achieved. The dual\u2010ratiometric response features of the DCNP@Cy\u2010MTD nanoprobe offer a significant advancement over traditional single\u2010signal or single\u2010modality imaging techniques. By providing enhanced accuracy and reliability, this probe allows for the diagnosis of hepatitis by monitoring the H<jats:sub>2<\/jats:sub>S, surpassing the capabilities of conventional histopathological methods, which provides a new way for more effective diagnostic strategies for liver diseases.<\/jats:p>","DOI":"10.1002\/smll.202501269","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T05:40:33Z","timestamp":1745473233000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Hydrogen Sulfide\u2010Activated NIR\u2010II Fluorescence\/NIR\u2010I Photoacoustic Dual\u2010Ratiometric Nanoprobe With Unique Recognition Reaction for Precise Visual Diagnosis of Hepatitis Disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Lixian","family":"Huang","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 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Lv","sequence":"additional","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 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidong","family":"Bin","sequence":"additional","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 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjin","family":"Zhao","sequence":"additional","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 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiying","family":"Li","sequence":"additional","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 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2560-042X","authenticated-orcid":false,"given":"Shulin","family":"Zhao","sequence":"additional","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 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengqiang","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources Key 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