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Published on: December 1, 2016
Self-luminescent photodynamic therapy using breast cancer targeted proteins
Eun Hye Kim1, Sangwoo Park2, Yun Kyu Kim3
1Department of Life Science, Hanyang University, Seoul 04763, Korea.
Abstract:
Despite the potential of photodynamic therapy (PDT), its comprehensive use in cancer treatment has not been achieved because of the nondegradable risks of photosensitizing drugs and limits of light penetration and instrumentation. Here, we present bioluminescence (BL)-induced proteinaceous PDT (BLiP-PDT), through the combination of luciferase and a reactive oxygen species (ROS)-generating protein (Luc-RGP), which is self-luminescent and degradable. After exposure to coelenterazine-h as a substrate for luciferase without external light irradiation, Luc-RGP fused with a small lead peptide-induced breast cancer cell death through the generation of BL-sensitive ROS in the plasma membrane. Even with extremely low light energy, BLiP-PDT exhibited targeted effects in primary breast cancer cells from patients and in in vivo tumor xenograft mouse models. These findings suggest that BLiP-PDT is immediately useful as a promising theranostic approach against various cancers.
Insights
Bioluminescence-induced proteinaceous photodynamic therapy (BLiP-PDT) offers a novel cancer treatment. This self-luminescent and degradable approach uses engineered proteins to generate reactive oxygen species (ROS) for targeted cancer cell death without external light.
Area of Science:
- Biochemistry
- Biotechnology
- Oncology
Background:
- Photodynamic therapy (PDT) faces limitations due to nondegradable photosensitizers and poor light penetration.
- Existing PDT methods require external light sources, limiting their clinical application.
- There is a need for safer, more effective PDT strategies for cancer treatment.
Purpose of the Study:
- To develop a novel, self-luminescent, and degradable photodynamic therapy approach.
- To overcome the limitations of traditional photodynamic therapy.
- To investigate the efficacy of bioluminescence-induced proteinaceous photodynamic therapy (BLiP-PDT) in cancer treatment.
Main Methods:
- Development of a fusion protein (Luc-RGP) combining luciferase and a reactive oxygen species (ROS)-generating protein.
- Utilizing coelenterazine-h as a substrate to induce bioluminescence and ROS generation without external light.
- Testing BLiP-PDT on patient-derived primary breast cancer cells and in vivo tumor xenograft mouse models.
Main Results:
- The engineered Luc-RGP protein successfully generated bioluminescence-sensitive ROS upon substrate addition.
- BLiP-PDT induced targeted cancer cell death in vitro, even with minimal light energy.
- Effective tumor regression was observed in vivo in mouse models, demonstrating targeted therapeutic effects.
Conclusions:
- BLiP-PDT represents a promising, self-sufficient therapeutic strategy for cancer treatment.
- The degradable nature of the protein component enhances safety compared to traditional PDT.
- BLiP-PDT shows potential as a theranostic approach for various cancers, overcoming key limitations of current PDT.
