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Theranostics 2015; 5(8):805-817. doi:10.7150/thno.11520 This issue Cite

Research Paper

Bioluminescence-Activated Deep-Tissue Photodynamic Therapy of Cancer

Yi Rang Kim^1,2,3, Seonghoon Kim¹, Jin Woo Choi^4,5, Sung Yong Choi², Sang-Hee Lee², Homin Kim², Sei Kwang Hahn⁶, Gou Young Koh^1,2, Seok Hyun Yun^1,5,7✉

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
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
6. Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 790-784, Korea.
7. Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, 40 Blossom St. Boston, MA 02114, USA

✉ Corresponding author: S. H. Andy Yun, Ph.D., Associate Professor. Tel: 1-617-768-8704; Email: syunharvard.edu

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/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.

Keywords: Photodynamic Therapy, Bioluminescence, Photosensitizers, Resonance Energy Transfer, Cancer, Photobiology, Photomedicine

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