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Recently, reports have indicated that Cerenkov luminescence-induced PDT may overcome the tissue penetration limitation of conventional PDT. However, the effectiveness of this method is controversial because of its low luminescence intensity. Herein, we developed a radiolabeled diethylenetriaminepentaacetic acid chelated Eu3+ (Eu-DTPA)\/photosensitizer (PS) loaded liposome (Eu\/PS-lipo) that utilizes ionizing radiation from radioisotopes for effective in vivo imaging and radioluminescence-induced PDT. We utilized Victoria blue-BO (VBBO) as a PS and observed an efficient luminescence resonance energy transfer between Eu-DTPA and VBBO. Furthermore, 64Cu-labeled Eu lipo demonstrated a strong radioluminescence with a 2-fold higher intensity than Cerenkov luminescence from free 64Cu. In our radioluminescence liposome, radioluminescence energy transfer showed a 6-fold higher energy transfer efficiency to VBBO than Cerenkov luminescence energy transfer (CLET). 64Cu-labeled Eu\/VBBO lipo (64Cu-Eu\/VBBO lipo) showed a substantial tumor uptake of up to 19.3%ID\/g by enhanced permeability and retention effects, as revealed by in vivo positron emission tomography. Finally, the PDT using 64Cu-Eu\/VBBO lipo demonstrated significantly higher in vitro and in vivo therapeutic effects than Cerenkov luminescence-induced PDT using 64Cu-VBBO lipo. This study envisions a great opportunity for clinical PDT application by establishing the radioluminescence liposome which has high tumor targeting and efficient energy transfer capability from radioisotopes.<\/jats:p>","DOI":"10.1021\/acsnano.0c04324","type":"journal-article","created":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T11:18:46Z","timestamp":1598008726000},"page":"13004-13015","source":"Crossref","is-referenced-by-count":57,"title":["Europium-Diethylenetriaminepentaacetic\nAcid Loaded\nRadioluminescence Liposome Nanoplatform for Effective Radioisotope-Mediated\nPhotodynamic Therapy"],"prefix":"10.1021","volume":"14","author":[{"given":"Wooseung","family":"Lee","sequence":"first","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyeon","family":"Jeon","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyeong","family":"Choi","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiwoo","family":"Oh","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaeun","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seongmoon","family":"Jung","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]},{"name":"Seoul National University Hospital , , ,","place":["Seoul, Republic of Korea, 03080"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3825-6293","authenticated-orcid":true,"given":"Changsoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]},{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8714-6317","authenticated-orcid":true,"given":"Sung-Joon","family":"Ye","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4368-6685","authenticated-orcid":true,"given":"Hyung-Jun","family":"Im","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]},{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,8,21]]},"reference":[{"key":"2026081718262219500_cit1","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nrc1071","article-title":"Photodynamic Therapy for Cancer","volume":"3","author":"Dolmans","year":"2003","journal-title":"Nat. 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Soc."},{"key":"2026081718262219500_cit5","doi-asserted-by":"publisher","first-page":"6597","DOI":"10.1039\/C6CS00271D","article-title":"Reactive Oxygen Species\nGenerating Systems Meeting Challenges of Photodynamic Cancer Therapy","volume":"45","author":"Zhou","year":"2016","journal-title":"Chem. Soc. Rev."},{"key":"2026081718262219500_cit6","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.7150\/thno.16141","article-title":"X-Ray Induced Photodynamic Therapy: A Combination of Radiotherapy\nand Photodynamic Therapy","volume":"6","author":"Wang","year":"2016","journal-title":"Theranostics"},{"key":"2026081718262219500_cit7","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1039\/C8PP00112J","article-title":"Using X-Rays in Photodynamic Therapy:\nAn Overview","volume":"17","author":"Larue","year":"2018","journal-title":"Photochem. Photobiol. 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Interfaces"},{"key":"2026081718262219500_cit10","doi-asserted-by":"publisher","first-page":"14971","DOI":"10.1021\/jacs.8b09374","article-title":"Magnetic Targeting\nof Nanotheranostics Enhances Cerenkov\nRadiation-Induced Photodynamic Therapy","volume":"140","author":"Ni","year":"2018","journal-title":"J. Am.\nChem. Soc."},{"key":"2026081718262219500_cit11","doi-asserted-by":"publisher","DOI":"10.1002\/wnan.1541","article-title":"Nanoparticles to Mediate X-Ray-Induced\nPhotodynamic Therapy and Cherenkov Radiation Photodynamic Therapy","volume":"11","author":"Cline","year":"2019","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol."},{"key":"2026081718262219500_cit12","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1038\/s41565-018-0142-y","article-title":"Is Cherenkov Luminescence\nBright Enough for Photodynamic\nTherapy?","volume":"13","author":"Pratx","year":"2018","journal-title":"Nat. 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Nanosci.\nNanotechnol."},{"key":"2026081718262219500_cit23","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1021\/ar0400894","article-title":"Benefiting\nfrom the Unique Properties of Lanthanide Ions","volume":"39","author":"Bunzli","year":"2006","journal-title":"Acc. Chem. Res."},{"key":"2026081718262219500_cit24","doi-asserted-by":"publisher","first-page":"6266","DOI":"10.1039\/c0cc05658h","article-title":"A Europium\u00ad(III) Chelate\nas an Efficient Time-Gated Luminescent Probe for Nitric Oxide","volume":"47","author":"Chen","year":"2011","journal-title":"Chem. Commun."},{"key":"2026081718262219500_cit25","doi-asserted-by":"publisher","first-page":"13442","DOI":"10.1021\/ja062990f","article-title":"A Europium\u00ad(III) Complex\nas an Efficient Singlet Oxygen Luminescence Probe","volume":"128","author":"Song","year":"2006","journal-title":"J. Am. Chem. 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Ion Exch."},{"key":"2026081718262219500_cit43","doi-asserted-by":"publisher","first-page":"8460","DOI":"10.1021\/ic0615574","article-title":"New Luminescent Europium\u00ad(III) Chelates\nfor DNA Labeling","volume":"45","author":"Nishioka","year":"2006","journal-title":"Inorg. Chem."},{"key":"2026081718262219500_cit44","doi-asserted-by":"publisher","first-page":"15468","DOI":"10.1021\/ja076005e","article-title":"Enantiopure,\nOctadentate Ligands as Sensitizers for Europium and Terbium Circularly\nPolarized Luminescence in Aqueous Solution","volume":"129","author":"Seitz","year":"2007","journal-title":"J. Am. Chem. 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Med. Imaging"},{"key":"2026081718262219500_cit49","doi-asserted-by":"publisher","DOI":"10.3389\/fphy.2019.00100","article-title":"Resonance\nEnergy\nTransfer: From Fundamental Theory to Recent Applications","volume":"7","author":"Jones","year":"2019","journal-title":"Front. Phys."},{"key":"2026081718262219500_cit50","doi-asserted-by":"publisher","first-page":"786462","DOI":"10.1155\/2014\/786463","article-title":"The Copper Radioisotopes: A Systematic\nReview with Special Interest to 64Cu","volume":"2014","author":"Niccoli\nAsabella","year":"2014","journal-title":"BioMed\nRes. 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