Development of Bioluminescence-Activated Photodynamic Therapy in Breast Cancer
- Title
- Development of Bioluminescence-Activated Photodynamic Therapy in Breast Cancer
- Other Titles
- 유방암에서의 생물발광 기반 광역학 치료법 개발
- Author
- 김은혜
- Alternative Author(s)
- 김은혜
- Advisor(s)
- 김영필
- Issue Date
- 2020-02
- Publisher
- 한양대학교
- Degree
- Doctor
- Abstract
- Photodynamic therapy (PDT), a form of clinically approved phototherapy, has been of intense interest as an alternative cancer treatment because it exerts selective damage toward malignant cells via reactive oxygen species (ROS) generation. PDT generally requires a chemical photosensitizer (PS), light irradiation and oxygen. However, despite the potential of photodynamic therapy (PDT), its comprehensive use in cancer treatment has not been achieved because of the non-degradable risks of PS and limits of light penetration and instrumentation. Here I demonstrate bioluminescence (BL)-induced PDT (BL-PDT), through the combination of luciferase and an ROS-generating protein (Luc-RGP), which is self-luminescent and degradable. After exposure to naturally occurring substrates without external light irradiation, Luc-RGP fused with a short lead peptide (termed Luc-RGP-LP) generated BL-sensitive ROS at close proximity to plasma membrane of breast cancer cells, leading to targeted cell death without damaging untargeted cells. Compared to the conventional LED light irradiation (~10 mW/cm2), this BL-promoted light showed approximately 103-fold lower energy level, but induced a surprisingly severe damage to breast cancer cells. Even with extremely low light energy, BL-PDT exhibited remarkable targeted effects in primary breast cancer cells from patients and in in vivo tumor xenograft mouse models. These findings suggest that BL-PDT is immediately useful as a new theranostic approach against various cancers.
- URI
- https://repository.hanyang.ac.kr/handle/20.500.11754/123448http://hanyang.dcollection.net/common/orgView/200000436800
- Appears in Collections:
- GRADUATE SCHOOL[S](대학원) > LIFE SCIENCE(생명과학과) > Theses (Ph.D.)
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