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In this study, we introduce a modular and scalable approach to transform a traditional TPE imaging dye into a highly effective type\u2010I photosensitizer (PS) through minimal chemical modification. The newly developed selenium\u2010bridged dye demonstrates pronounced two\u2010photon absorption, efficient ROS generation upon TPE, and strong antitumor activity both in vitro and in hypoxic in vivo tumor environments. For subcellular targeting, we conjugated organelle\u2010specific functional groups to produce a series of derivatives, thereby achieving accurate ROS localization and improved PDT efficacy. Leveraging the amphiphilic properties of these PSs, we established a self\u2010assembled dye\u2010combination micelle (DCM) approach that enables the co\u2010assembly of membrane\u2010 and mitochondria\u2010targeted derivatives into stable, carrier\u2010free nanoparticles. This multi\u2010dye strategy facilitates enhanced phototoxicity by simultaneously impairing multiple organelle functions. Additional surface modification using the RGD (Arg\u2010Gly\u2010Asp) peptide sequence imparts tumor selectivity through \u03b1\n                    <jats:sub>v<\/jats:sub>\n                    \u03b2\n                    <jats:sub>3<\/jats:sub>\n                    integrin\u2010mediated uptake, yielding DCM nanoparticles that selectively induce phototoxic effects in cancer cells while sparing healthy tissue. Importantly, this platform demonstrates spatially restricted, two\u2010photon\u2010triggered therapeutic efficacy in freshly excised human colon tumor tissue, emphasizing its potential for clinical translation.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202505557","type":"journal-article","created":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T07:18:45Z","timestamp":1769325525000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dye\u2010Combination Micelles for Two\u2010Photon Phototherapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Dong Joon","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Chemistry and Department of Energy Systems Research Ajou University  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinayak","family":"Juvekar","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Department of Energy Systems Research Ajou University  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Health Science and Engineering Hubei University  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong Kyu","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Department of Energy Systems Research Ajou University  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong Beom","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Department of Energy Systems Research Ajou University  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Cheol","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Department of Energy Systems Research Ajou University  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Sauraj","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Department of Energy Systems Research Ajou University  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abijith Karyapallathil","family":"Sadashivan","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Department of Energy Systems Research Ajou University  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myoung Ki","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Department of Energy Systems Research Ajou University  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gil Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Ajou University School of Medicine  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae Jun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Ajou University School of Medicine  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyuk","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Department of Energy Systems Research Ajou University  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Jae","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Ajou University School of Medicine  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihong","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Health Science and Engineering Hubei University  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4112-9009","authenticated-orcid":false,"given":"Hwan Myung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Department of Energy Systems Research Ajou University  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,24]]},"reference":[{"issue":"1","key":"e_1_2_7_2_1","first-page":"10","article-title":"Cancer Statistics","volume":"75","author":"Siegel R. 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