title: Mitochondrion-Anchoring Photosensitizer with Aggregation-Induced Emission Characteristics Synergistically Boosts the Radiosensitivity of Cancer Cells to Ionizing Radiation.
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-controlled1O2generation, 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 elevated1O2environment in the mitochondria. More importantly, increasing intracellular level of1O2originated 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).
authors.affiliation: 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), Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Chris Y Y
authors.initials: CY
authors.lastname: Yu
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Huae
authors.initials: H
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education and College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Shenglu
authors.initials: S
authors.lastname: Ji
authors.affiliation: 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), Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Ryan T K
authors.initials: RT
authors.lastname: Kwok
authors.affiliation: 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), Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Jacky W Y
authors.initials: JW
authors.lastname: Lam
authors.affiliation: Department of Geriatric Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China.|Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education and College of Life Sciences, Nankai University, Tianjin, 300071, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Ding
authors.affiliation: 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), Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Ben Zhong
authors.initials: BZ
authors.lastname: Tang
mesh_terms: D006046:Gold; D053768:Metal Nanoparticles; D008928:Mitochondria; D017319:Photosensitizing Agents; D011836:Radiation Tolerance; D011839:Radiation, Ionizing
chemical_list: D017319:Photosensitizing Agents; D006046:Gold
keywords: aggregation-induced emission; mitochondrial targeting; photosensitizer; radiation therapy; radiosensitization