The long-term goal of this proposed research is to lower recurrence and improve survival in breast cancer treatment. In early breast cancer, surgery can remove primary tumors, but undetected, residual cancer cells develop into life-threatening recurrence. The proposed research will develop and test novel photodynamic therapy (PDT) for killing cancer cells in the tumor margin and regional lymph nodes with minimal damage to normal tissues and the lymphatic system (high therapeutic index). Conventional PDT uses photosensitizers as drug that, when activated by light, produce free radicals, causing damages to cells. With this unique mechanism, PDT can be an effective modality to kill chemo-resistant cells and TNBC subtypes. However, current PDT is not a viable option for breast cancer treatment because the limited penetration of light in tissue prevents it from being effective at depths beyond several millimeters. This project explores an innovative solution to this problem in which bioluminescence (BL) of molecules locally injected into the tissue enables PDT at deep regions that are not accessible by external light illumination. This technique termed BL-PDT will be developed and valuated in state-of-the-art murine models, including patient-derived xenograft murine models and genetically induced spontaneous models of breast cancer, as well as various heterogeneous breast cancer cell lines in vitro. There are three specific aims: (1) Develop and test luciferase-photosensitizer conjugates for treating metastatic breast cancer. Non-toxic organic agents will be developed and tested. (2) Establish optimal therapeutic index for targeted BL-PDT for breast cancer. (3) Develop and validate adjuvant BL-PDT to treat residual disease in the breast and LNs to lower recurrence and increase survival. This project is expected to demonstrate the preclinical feasibility of BL-PDT as a novel, effective, minimally invasive, adjuvant therapy and will add to the existing arsenal of tools to combat breast cancer. The long-term impact of this project is high as it can reduce recurrence and improve prognosis. Besides invasive breast cancer, BL-PDT is expected to be applicable to ductal carcinoma in situ and other types of recurrent cancers. BL-PDT removes the limitations of near infrared agents necessary in PDT currently. Furthermore, biochemical activation by BL energy may have far-reaching impacts in light- based photomedicine beyond PDT.

Public Health Relevance

This proposal is relevant to public health because it will develop a novel treatment method to reduce the risk of local recurrence of breast cancer after surgery. The novel therapy may improve the mortality, morbidity, and cost-burden of breast cancer patients. Therefore, the proposed research is relevant to the NIH's mission of fostering innovative research strategies to increase the nation's ability to improve the treatment of disease.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Buchsbaum, Jeffrey
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Kim, Seonghoon; Jo, HyeongChan; Jeon, Mijeong et al. (2017) Luciferase-Rose Bengal conjugates for singlet oxygen generation by bioluminescence resonance energy transfer. Chem Commun (Camb) 53:4569-4572
Humar, Matjaž; Upadhya, Avinash; Yun, Seok Hyun (2017) Spectral reading of optical resonance-encoded cells in microfluidics. Lab Chip 17:2777-2784
Yun, Seok Hyun; Kwok, Sheldon J J (2017) Light in diagnosis, therapy and surgery. Nat Biomed Eng 1:
Humar, Matjaž; Yun, Seok Hyun (2017) Whispering-gallery-mode emission from biological luminescent protein microcavity assemblies. Optica 4:222-228
Yetisen, Ali K; Jiang, Nan; Fallahi, Afsoon et al. (2017) Glucose-Sensitive Hydrogel Optical Fibers Functionalized with Phenylboronic Acid. Adv Mater 29:
Nizamoglu, Sedat; Gather, Malte C; Humar, Matjaž et al. (2016) Bioabsorbable polymer optical waveguides for deep-tissue photomedicine. Nat Commun 7:10374
Kwok, Sheldon J J; Choi, Myunghwan; Bhayana, Brijesh et al. (2016) Two-photon excited photoconversion of cyanine-based dyes. Sci Rep 6:23866
Koo, Heebeom; Lee, Jeong Heon; Bao, Kai et al. (2016) Site-Specific In Vivo Bioorthogonal Ligation via Chemical Modulation. Adv Healthc Mater 5:2510-2516
Guo, Jingjing; Liu, Xinyue; Jiang, Nan et al. (2016) Highly Stretchable, Strain Sensing Hydrogel Optical Fibers. Adv Mater 28:10244-10249
Kim, Ki Su; Kim, Hyemin; Park, Yunji et al. (2016) Noninvasive Transdermal Vaccination Using Hyaluronan Nanocarriers and Laser Adjuvant. Adv Funct Mater 26:2512-2522

Showing the most recent 10 out of 12 publications