Mitochondrion‐Anchoring Photosensitizer with Aggregation‐Induced Emission Characteristics Synergistically Boosts the Radiosensitivity of Cancer Cells to Ionizing Radiation |
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| Authors: | Chris Y Y Yu Huae Xu Shenglu Ji Ryan T K Kwok Jacky W Y Lam Xiaolin Li Sunil Krishnan Dan Ding Ben Zhong Tang |
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| Affiliation: | 1. Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, State Key Laboratory of Neuroscienceand Division of Biomedical Engineering, The Hong Kong University of Science and Technology (HKUST), Kowloon, Hong Kong, China;2. Department of Pharmacy, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China;3. State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education and College of Life Sciences, Nankai University, Tianjin, China;4. Department of Geriatric Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China;5. Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA |
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| Abstract: | The first mitochondrion‐anchoring photosensitizer that specifically generates singlet oxygen (1O2) in mitochondria under white light irradiation that can serve as a highly effective radiosensitizer is reported here, significantly sensitizing cancer cells to ionizing radiation. An aggregation‐induced emission luminogen (AIEgen), namely DPA‐SCP, is rationally designed with α‐cyanostilbene as a simple building block to reveal AIE, diphenylamino (DPA) group as a strong electron donating group to benefit red emission and efficient light‐controlled 1O2 generation, as well as a pyridinium salt as the targeting moiety to ensure specific mitochondrial localization. The AIE signature endows DPA‐SCP with the capacity to visualize mitochondria in a fluorescence turn‐on mode. It is found that under optimized experimental condition, DPA‐SCP with white light does not lead to apoptosis/death of cancer cells, whereas provides an elevated 1O2 environment in the mitochondria. More importantly, increasing intracellular level of 1O2 originated from mitochondria is demonstrated to be a generic method to enhance the radiosensitivity of cancer cells with a supra‐additive synergistic effect of “0 + 1 > 1.” Noteworthy is that “DPA‐SCP + white light” achieves a high SER10 value of 1.62, which is much larger than that of the most popularly used radiosensitizers, gold nanoparticles (1.19), and paclitaxel (1.32). |
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| Keywords: | aggregation‐induced emission mitochondrial targeting photosensitizer radiation therapy radiosensitization |
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