title: Bioluminescence-activated deep-tissue photodynamic therapy of cancer.
abstract: Optical energy can trigger a variety of photochemical processes useful for therapies. Owing to the shallow penetration of light in tissues, however, the clinical applications of light-activated therapies have been limited. Bioluminescence resonant energy transfer (BRET) may provide a new way of inducing photochemical activation. Here, we show that efficient bioluminescence energy-induced photodynamic therapy (PDT) of macroscopic tumors and metastases in deep tissue. For monolayer cell culture in vitro incubated with Chlorin e6, BRET energy of about 1 nJ per cell generated as strong cytotoxicity as red laser light irradiation at 2.2 mW/cm(2) for 180 s. Regional delivery of bioluminescence agents via draining lymphatic vessels killed tumor cells spread to the sentinel and secondary lymph nodes, reduced distant metastases in the lung and improved animal survival. Our results show the promising potential of novel bioluminescence-activated PDT.
authors.affiliation: 1. Graduate School of Nanoscience and Technology (WCU), Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yusong-Gu, Daejon 305-701, Korea ; 2. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yusong-Gu, Daejon 305-701, Korea ; 3. Department of Oncology, Asan Medical Center, Univ. Ulsan College of Medicine, Seoul , Korea.
authors.forename: Yi Rang
authors.initials: YR
authors.lastname: Kim
authors.affiliation: 1. Graduate School of Nanoscience and Technology (WCU), Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yusong-Gu, Daejon 305-701, Korea.
authors.forename: Seonghoon
authors.initials: S
authors.lastname: Kim
authors.affiliation: 4. Department of Pharmacology, Wonkwang Institute of Dental Research, School of Dentistry, Wonkwang University, Iksan, Chonbuk, 570-749, Korea ; 5. Wellman Center for Photomedicine, Massachusetts General Hospital, 65 Landsdowne St. UP-525, Cambridge, MA 02139, USA.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Choi
authors.affiliation: 2. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yusong-Gu, Daejon 305-701, Korea.
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Choi
authors.affiliation: 2. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yusong-Gu, Daejon 305-701, Korea.
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: 2. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yusong-Gu, Daejon 305-701, Korea.
authors.forename: Homin
authors.initials: H
authors.lastname: Kim
authors.affiliation: 6. Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 790-784, Korea.
authors.forename: Sei Kwang
authors.initials: SK
authors.lastname: Hahn
authors.affiliation: 1. Graduate School of Nanoscience and Technology (WCU), Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yusong-Gu, Daejon 305-701, Korea ; 2. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yusong-Gu, Daejon 305-701, Korea.
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
authors.affiliation: 1. Graduate School of Nanoscience and Technology (WCU), Korea Advanced Institute of Science and Technology, 291 Daehak-Ro, Yusong-Gu, Daejon 305-701, Korea ; 5. Wellman Center for Photomedicine, Massachusetts General Hospital, 65 Landsdowne St. UP-525, Cambridge, MA 02139, USA ; 7. Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, 40 Blossom St. Boston, MA 02114, USA.
authors.forename: Seok Hyun
authors.initials: SH
authors.lastname: Yun
mesh_terms: D000818:Animals; D002735:Chlorophyllides; D004195:Disease Models, Animal; D006801:Humans; D007834:Lasers; D049449:Luminescence; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000188:drug therapy*; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000378:metabolism*
chemical_list: D002735:Chlorophyllides; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C062985:phytochlorin
keywords: Bioluminescence; Cancer; Photobiology; Photodynamic Therapy; Photomedicine; Photosensitizers; Resonance Energy Transfer