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Early diagnosis remains challenging, and its strong propensity for metastasis is a major contributor to poor patient prognosis. Current approaches for surgical guidance and photodynamic therapy (PDT) in CRC are hindered by key limitations. Imaging techniques used for intraoperative navigation often lack sufficient sensitivity and specificity, while conventional PDT often employs \u201calways\u2010on\u201d photosensitizers that lack tumor selectivity, posing a risk of collateral damage to healthy tissues. To address these limitations, this study leveraged the overexpression of \u03b2\u2010N\u2010acetylhexosaminidase (Hex) in CRC to design and develop an activatable near\u2010infrared phototheranostic probe (INA) for tumor diagnosis and therapy. In vitro experiments demonstrated that INA is effectively activated by endogenously overexpressed Hex in CRC cells. Under light irradiation, it exhibits potent phototoxicity against CRC cells and three\u2010dimensional tumor spheroids, with minimal dark toxicity. In tumor\u2010bearing mouse models, INA enabled tumor\u2010specific fluorescence imaging, real\u2010time detection of microtumors for surgical navigation, and effective PDT, while demonstrating favorable biocompatibility. With its simple molecular architecture, INA is positioned as a highly competitive and readily translatable candidate for integrated diagnosis and therapy in CRC.<\/jats:p>","DOI":"10.1002\/adhm.71585","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:51:06Z","timestamp":1786683066000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Phototheranostic Probe Activated by \u03b2\u2010N\u2010Acetylhexosaminidase for Fluorescence Navigation Surgery and Photodynamic Therapy of Colorectal Cancer"],"prefix":"10.1002","volume":"15","author":[{"given":"Yongchang","family":"Qiao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical Engineering Dalian University of Technology  Dalian 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