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In Photodynamic Therapy (PDT), it has been noted that continuous\u2010wave and pulsed lasers give comparable results for a variety of tumors, but the conditions for increased tumor\u2010to\u2010peritumoral tissue selectivity have never been reported. This work presents a model that explains how pulsed lasers, in combination with photosensitizers, can offer selective and in\u2010depth tumor ablation. It is shown that the photosensitizer absorption must be saturated to obtain the FLASH effect. The importance of the number of laser pulses to destroy tumor tissue and spare normal tissue is demonstrated. The predictions of the model and the superiority of FLASH\u2010PDT are validated with the treatment of subcutaneous CT26 and orthotopic 4T1 tumors models. Notably, FLASH\u2010PDT with redaporfin significantly increases the overall survival of mice with 4\u00a0mm orthotopic 4T1 tumors and lung metastasis. FLASH\u2010PDT allows for the use of order\u2010of\u2010magnitude higher drug or light doses without affecting healthy tissues, while promoting selective and deeper tumor treatments.<\/jats:p>","DOI":"10.1002\/advs.202513199","type":"journal-article","created":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T10:40:18Z","timestamp":1763289618000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Flash Photodynamic Therapy \u2013 How the Saturation of Photosensitizer Absorption Enables Selective and Deeper Tumor Treatments"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3223-4819","authenticated-orcid":false,"given":"Luis G.","family":"Arnaut","sequence":"first","affiliation":[{"name":"CQC\u2010IMS Department of Chemistry University of Coimbra  Coimbra 3004\u2010535 Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9339-7259","authenticated-orcid":false,"given":"F\u00e1bio A.","family":"Schaberle","sequence":"additional","affiliation":[{"name":"CQC\u2010IMS Department of Chemistry University of Coimbra  Coimbra 3004\u2010535 Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9607-6653","authenticated-orcid":false,"given":"Jos\u00e9","family":"Sereno","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT) University of Coimbra  Coimbra 3000\u2010548 Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0624-8819","authenticated-orcid":false,"given":"L\u00edgia C.","family":"Gomes\u2010da\u2010Silva","sequence":"additional","affiliation":[{"name":"CQC\u2010IMS Department of Chemistry University of Coimbra  Coimbra 3004\u2010535 Portugal"}]}],"member":"311","published-online":{"date-parts":[[2025,11,16]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-022-00697-z"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008973"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1103\/RevModPhys.96.035002"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2023.07.042"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/c5pp00132c"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-1097.1984.tb03414.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.1900110504"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.1900130306"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02032503"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02133208"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.1992.tb00090.x"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00179303"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1364\/AO.36.007257"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6690361"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/HP.0b013e3182983fd4"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0584-8547(82)80082-7"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920106777950843"},{"key":"e_1_2_8_18_1","first-page":"2330","volume":"36","author":"Dougherty T. 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