期刊
ADVANCED MATERIALS
卷 29, 期 15, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.201606167
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资金
- National Basic Research Program of China (973 Program) [2013CB834701, 2013CB834702]
- University Grants Committee of Hong Kong [AoE/P-03/08]
- Research Grants Council of Hong Kong [16301614, 16305015, N_HKUST604/14]
- Innovation and Technology Commission [ITC-CNERC14SC01, RE: ITCPD/17-9]
- NSFC [51622305, 31571011, 81472781, 81672411, 81372274, 81501591, 8141101080]
- PCSIRT [IRT13023]
- Science & Technology Project of Tianjin of China [15JCYBJC29800]
- Guangdong Innovative Research Team Program of China [201101C0105067115]
- Science and Technology Planning Project of Guangdong Province [2014A030313033, 2014A050503037]
The first mitochondrion-anchoring photosensitizer that specifically generates singlet oxygen (O-1(2)) 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 alpha-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 O-1(2) 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 O-1(2) environment in the mitochondria. More importantly, increasing intracellular level of O-1(2) 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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