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Here we present a modular strategy to generate small\u2010molecule, singlet\u2010oxygen\u2010generating (\n                    <jats:sup>1<\/jats:sup>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010genic) photosensitizers for controlling and decoding cytoskeletal networks. Single\u2010step installation of a sulfamide\u2010PEG\n                    <jats:sub>2<\/jats:sub>\n                    \u2010ligand onto rhodamine photosensitizer scaffolds yields binding\u2010activated probes that mainly exist as the non\u2010excitable spirolactams in solution but largely switch to\n                    <jats:sup>1<\/jats:sup>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010producing zwitterions upon binding to microtubules or F\u2010actin. Continuous illumination in confocal microscopy generates a burst of\n                    <jats:sup>1<\/jats:sup>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    , driving highly localized oxidation and second\u2010timescale collapse of filament\u2010organelle\/protein networks, revealing key roles for microtubules in lysosome transport and mitochondrial dynamics. In parallel, light\u2010tunable mild\n                    <jats:sup>1<\/jats:sup>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    generation enables selective proteome\u2010wide proximity labeling of microtubule\u2010 and F\u2010actin\u2010associated networks, unveiling previously uncharacterized dual interactors at the microtubule\u2010F\u2010actin interface. This modular platform provides an effective tool for genetic\u2010manipulation\u2010free mapping and spatiotemporally controlled, localized oxidative perturbation of endogenous networks.\n                  <\/jats:p>","DOI":"10.1002\/anie.3832427","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T19:22:11Z","timestamp":1784661731000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Binding\u2010Activated\n                    <sup>1<\/sup>\n                    O\n                    <sub>2<\/sub>\n                    \u2010Genic Photosensitizers for Live\u2010Cell Control and Proteomic Mapping of Cytoskeletal Networks"],"prefix":"10.1002","volume":"65","author":[{"given":"Gang","family":"Xing","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences MOE Key Laboratory of Smart Drug Delivery, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases Endoscopy Center and Endoscopy Research Institute Zhongshan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8061-7898","authenticated-orcid":false,"given":"Zhihao","family":"Dong","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences MOE Key Laboratory of Smart Drug Delivery, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases Endoscopy Center and Endoscopy Research Institute Zhongshan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Sun","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Key Laboratory of RNA Innovation Science and Engineering Chinese Academy of Sciences University of Chinese Academy of Sciences  Shanghai 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Thet","family":"Htar","sequence":"additional","affiliation":[{"name":"School of Pharmacy Monash University Malaysia  Selangor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Brain Function and Disorders MOE Frontiers Center for Brain Science Institutes of Brain Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Johnsson","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology Max Planck Institute for Medical Research  Heidelberg Germany"},{"name":"Institute of Chemical Sciences and Engineering \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences MOE Key Laboratory of Smart Drug 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