Kim, Yi RangKim, SeonghoonChoi, Jin WooChoi, Sung YongLee, Sang-HeeKim, HominHahn, Sei KwangKoh, Gou YoungYun, Seok Hyun2015-06-022015Kim, Yi Rang, Seonghoon Kim, Jin Woo Choi, Sung Yong Choi, Sang-Hee Lee, Homin Kim, Sei Kwang Hahn, Gou Young Koh, and Seok Hyun Yun. 2015. “Bioluminescence-Activated Deep-Tissue Photodynamic Therapy of Cancer.” Theranostics 5 (8): 805-817. doi:10.7150/thno.11520. http://dx.doi.org/10.7150/thno.11520.1838-7640http://nrs.harvard.edu/urn-3:HUL.InstRepos:16120994Optical 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/cm2 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.en-USPhotodynamic TherapyBioluminescencePhotosensitizersResonance Energy TransferCancerPhotobiologyPhotomedicineJournal Article2015-06-0210.7150/thno.11520