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Here, we report a \u03b3\u2010glutamyltransferase (GGT)\u2010activatable, hydrophilicity\u2010switchable, and self\u2010immobilizing near\u2010infrared photosensitizer,\n                    <jats:bold>GGT\u2010PS2<\/jats:bold>\n                    . Initially hydrophilic and photoinactive,\n                    <jats:bold>GGT\u2010PS2<\/jats:bold>\n                    undergoes enzymatic cleavage by tumor\u2010associated GGT, triggering a hydrophilic\u2010to\u2010hydrophobic transition and generating a reactive quinone methide intermediate for covalent immobilization. This process simultaneously activates near\u2010infrared fluorescence and singlet oxygen production. In vitro studies demonstrate GGT\u2010specific activation, efficient protein binding, and enhanced photodynamic performance compared to control analogs. In a HeLa tumor xenograft model,\n                    <jats:bold>GGT\u2010PS2<\/jats:bold>\n                    achieves selective tumor accumulation and prolonged retention, resulting in complete tumor regression after a single intravenous administration with light irradiation, without observable toxicity or recurrence. This \u201cone\u2010to\u2010multi\u201d design provides an effective strategy to overcome the solubility\u2013retention trade\u2010off, offering a promising platform for precision PDT.\n                  <\/jats:p>","DOI":"10.1002\/adhm.71730","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:49:31Z","timestamp":1789534171000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Hydrophilicity\u2010Switchable, Self\u2010Immobilizing Near\u2010Infrared Photosensitizer for \u03b3\u2010Glutamyltransferase\u2010Activated Precision Photodynamic Therapy"],"prefix":"10.1002","author":[{"given":"Yiru","family":"Ding","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of New Drug Design Frontiers Science Center for Materiobiology and Dynamic Chemistry Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youyan","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of New Drug Design Frontiers Science Center for Materiobiology and Dynamic Chemistry Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqian","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of New Drug Design Frontiers Science Center for Materiobiology and Dynamic Chemistry Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology  Shanghai P. R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1071"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20114"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.62347\/JOUT3260"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOO.0000000000000521"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20150942"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201805246"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.1c00381"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CS00173B"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3SC07006A"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2CS00673A"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00075a026"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511020103"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/818570"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.18798"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6101511"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432\u20101033.1991.tb16391.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097\u20100142(20000215)88:4<761::AID\u2010CNCR5>3.0.CO;2\u20105"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2008.11.016"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109378(98)70365\u20105"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.323"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201013847\u20106"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010019\u20106250\u20108"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201800370"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2016.03.021"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201702210"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.7b05022"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2018.08.056"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.0c02954"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0AN02232B"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2018033118"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.2c04894"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4SC06459C"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/asia.70238"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/20014091084227"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002823"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201704793"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsabm.1c00354"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11426\u2010020\u20109947\u20104"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202317773"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202408559"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9SC03355F"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7SC05115H"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9CC01253B"}],"container-title":["Advanced 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