{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:05:24Z","timestamp":1793412324130,"version":"4.5.0"},"reference-count":57,"publisher":"Wiley","issue":"28","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Conventional \u201calways\u2010on\u201d phototherapies often suffer from insufficient tumor selectivity and suboptimal utilization of reactive oxygen species (ROS) and photothermal therapy, limiting their clinical efficacy. Herein, a novel activatable, single\u2010component theranostic system was developed for overcoming these limitations via tumor microenvironment\u2010triggered dual\u2010modal phototherapy. A heptamethine cyanine\u2010based photosensitizer, Cu\u2010Icy\u2010H\n                    <jats:sub>2<\/jats:sub>\n                    S, was rationally designed by integrating an iodo\u2010substituted cyanine fluorophore with a Cu\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    \u2013cyclen complex. This molecule remains photoinactive under physiological conditions but undergoes rapid activation in the presence of elevated hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S), a tumor\u2010associated biomarker. The H\n                    <jats:sub>2<\/jats:sub>\n                    S\u2010mediated reaction triggers in situ formation of CuS nanoparticles and simultaneously liberates a photoactive cyanine derivative (Icy\u2010H\n                    <jats:sub>2<\/jats:sub>\n                    S). This dual transformation enables concurrent photodynamic therapy (PDT) through ROS generation and photothermal therapy (PTT) via CuS\u2010mediated heat production under near\u2010infrared (NIR) irradiation. Moreover, the fluorescence of Icy\u2010H\n                    <jats:sub>2<\/jats:sub>\n                    S facilitates real\u2010time NIR imaging, allowing precise tumor localization and therapy guidance. In vivo studies in 4T1 tumor\u2010bearing mice demonstrated significant tumor inhibition with minimal systemic toxicity, confirming the potent synergistic efficacy of the PDT\u2010PTT combination strategy. This work introduces a reasonable design for H\n                    <jats:sub>2<\/jats:sub>\n                    S\u2010responsive, single\u2010component theranostic agents and addresses the intrinsic photothermal instability of cyanine dyes by leveraging in situ CuS nanoparticle formation for enhanced photothermal conversion.\n                  <\/jats:p>","DOI":"10.1002\/smll.202512555","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T12:32:41Z","timestamp":1775046761000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tumor Microenvironment Activated Heptamethine Cyanine Photosensitizer for In Situ CuS Nanoparticle Generation Triggering Near Infrared Fluorescence Imaging and Synergistic Photothermal\/Photodynamic Therapy"],"prefix":"10.1002","volume":"22","author":[{"given":"Qian","family":"An","sequence":"first","affiliation":[{"name":"Key Laboratory of Catalysis and Energy Materials Chemistry of Ministry of Education &amp; Key Laboratory of Analytical Chemistry of the State Ethnic Affairs Commission, College of Chemistry and Materials Science South\u2010Central Minzu University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengze","family":"Su","sequence":"additional","affiliation":[{"name":"Key Laboratory of Catalysis and Energy Materials Chemistry of Ministry of Education &amp; Key Laboratory of Analytical Chemistry of the State Ethnic Affairs Commission, College of Chemistry and Materials Science South\u2010Central Minzu University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yicheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Catalysis and Energy Materials Chemistry of Ministry of Education &amp; Key Laboratory of Analytical Chemistry of the State Ethnic Affairs Commission, College of Chemistry and Materials Science South\u2010Central Minzu 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Chemistry of Ministry of Education &amp; Key Laboratory of Analytical Chemistry of the State Ethnic Affairs Commission, College of Chemistry and Materials Science South\u2010Central Minzu University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongping","family":"Deng","sequence":"additional","affiliation":[{"name":"Renmin Hospital of Wuhan University Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxing","family":"Xiong","sequence":"additional","affiliation":[{"name":"Renmin Hospital of Wuhan University Wuhan University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanying","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Catalysis and Energy Materials Chemistry of Ministry of Education &amp; Key Laboratory of Analytical Chemistry of the State Ethnic Affairs Commission, College of Chemistry and Materials Science South\u2010Central Minzu 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