{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T16:48:40Z","timestamp":1791650920144,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"42","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22377153"],"award-info":[{"award-number":["22377153"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22277148"],"award-info":[{"award-number":["22277148"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100725"],"award-info":[{"award-number":["82100725"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82504564"],"award-info":[{"award-number":["82504564"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22377156"],"award-info":[{"award-number":["22377156"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515011917"],"award-info":[{"award-number":["2023A1515011917"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515011751"],"award-info":[{"award-number":["2024A1515011751"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024M763828"],"award-info":[{"award-number":["2024M763828"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2026,10,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Photodynamic therapy (PDT) is a clinically promising, minimally invasive cancer treatment offering precise spatiotemporal control. However, achieving preferential tumor accumulation remains a critical challenge, which limits therapeutic efficacy and induces off\u2010target toxicity. Here, we introduce the mitoGPS (mitochondrial G\u2010quadruplex\u2013targeting photosensitizer) strategy, a rational design framework for developing photosensitizers (PSs) with prolonged intratumoral retention through targeting mitochondrial DNA G\u2010quadruplexes (mtDNA G4s). This approach leverages the unique structural features and biological attributes of mtDNA G4s, which are increasingly implicated in cancer cell metabolism and survival, to achieve preferential photosensitizer accumulation and action within tumor mitochondria. By integrating molecular generation, G4\u2010specific docking simulations, and evaluation of photosensitizing properties, we established a modular workflow for the discovery of mitoGPS. Using this pipeline, we designed and identified\n                    <jats:bold>A1<\/jats:bold>\n                    , a lead mitoGPS compound.\n                    <jats:bold>A1<\/jats:bold>\n                    exhibits preferential mitochondrial localization in tumor cells, with its retention influenced by interactions with mtDNA G4s, and generates predominantly Type I reactive oxygen species (ROS) upon light activation. The resulting mitochondrial oxidative stress disrupts mitochondrial integrity and engages apoptosis\u2010associated and ferroptosis\u2010associated responses. Our work supports mtDNA G4\u2010associated recognition as a strategy for improving the subcellular precision of PDT and provides a generalizable framework for developing mitochondria\u2010directed phototherapies.\n                  <\/jats:p>","DOI":"10.1002\/anie.4238416","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T09:22:35Z","timestamp":1787390555000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["MitoGPS: A Mitochondrial DNA G\u2010Quadruplex\u2010Targeting Strategy for Tumor\u2010Preferential Type I Photodynamic Therapy"],"prefix":"10.1002","volume":"65","author":[{"given":"Yu\u2010Hui","family":"Guo","sequence":"first","affiliation":[{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao\u2010Hui","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010Min","family":"Huang","sequence":"additional","affiliation":[{"name":"La Trobe University Department of Biochemistry and Chemistry La Trobe Institute for Molecular Science  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui\u2010Xue","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Min","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao\u2010Lin","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Hao","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou China"},{"name":"Department of Pharmacy The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6411-9711","authenticated-orcid":false,"given":"Xiu\u2010Cai","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Biomedical and Pharmaceutical Sciences Guangdong University of Technology  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6211-5482","authenticated-orcid":false,"given":"Zhi\u2010Shu","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Yong","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Food and Drug Shenzhen Polytechnic University  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Heng","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Wu","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Radiology Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9118-2185","authenticated-orcid":false,"given":"Shuo\u2010Bin","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010020\u20100410\u20102"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pdpdt.2022.102836"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.21368"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202415673"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202410142"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CS01370F"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CS00173B"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15030585"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15092257"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202423348"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c17268"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202408581"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmaterialslett.4c01214"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01653"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.07.002"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202408874"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1595"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c06808"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00042"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12010004"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/ijbc\/3013009"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867325666180228165527"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1061"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad535"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2024.05.003"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c08860"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad365"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/narcan\/zcab038"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202300162"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c00435"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.4c00234"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035586"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201004771\u2010y"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102164\u201015\u2010677"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3cs35531d"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.780"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2SC06445F"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5SC01733E"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpca.2c08937"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw006"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.4238416","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.4238416","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.4238416","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:50:01Z","timestamp":1791647401000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.4238416"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,22]]},"references-count":40,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2026,10,12]]}},"alternative-id":["10.1002\/anie.4238416"],"URL":"https:\/\/doi.org\/10.1002\/anie.4238416","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,22]]},"assertion":[{"value":"2026-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e4238416"}}