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Despite the steady advances in imaging devices, there is a scarcity of fluorophores available to achieve optimal FGS. Here, 1) a pH\u2010sensitive near\u2010infrared fluorophore that exhibits rapid signal changes in acidic tumor microenvironments (TME) caused by the attenuation of intramolecular quenching, 2) the inherent targeting for cancer based on chemical structure (structure inherent targeting, SIT), and 3) mitochondrial and lysosomal retention are reported. After topical application of <jats:bold>PH08<\/jats:bold> on peritoneal tumor regions in ovarian cancer\u2010bearing mice, a rapid fluorescence increase (&lt; 10\u00a0min), and extended preservation of signals (&gt; 4 h post\u2010topical application) are observed, which together allow for the visualization of submillimeter tumors with a high tumor\u2010to\u2010background ratio (TBR &gt;\u00a05.0). In addition, <jats:bold>PH08<\/jats:bold> is preferentially transported to cancer cells via organic anion transporter peptides (OATPs) and colocalizes in the mitochondria and lysosomes due to the positive charges, enabling a long retention time during FGS. <jats:bold>PH08<\/jats:bold> not only has a significant impact on surgical and diagnostic applications but also provides an effective and scalable strategy to design therapeutic agents for a wide array of cancers.<\/jats:p>","DOI":"10.1002\/advs.202201416","type":"journal-article","created":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T03:08:49Z","timestamp":1652497729000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Topical pH Sensing NIR Fluorophores for Intraoperative Imaging and Surgery of Disseminated Ovarian 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