Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 157, Issue -, Pages 599-609Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2018.08.024
Keywords
Photodynamic therapy; BODIPY; Mitochondria-targeting
Categories
Funding
- NSFC [21572039]
- STCSM [15401901900]
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In this paper, a series of novel BODIPY-based photosensitizers have been designed and synthesized for photodynamic therapy. BODIPY3 was screened out as the most potential photosensitizer due to its excellent optical properties, high singlet oxygen efficiency and good photostability. However, as an organic photosensitizer, BODIPY3 still suffered from the drawbacks of insolubility and instability in aqueous system. In view of these problems, DSPE-PEG2000 was used to trap BODIPY3 into the hydrophobic core of micelles to obtain well-dispersing nano complexes BODIPY3-PEG(3) in aqueous system. More importantly, BODIPY3-PEG(3) not only has better solubility and stability in aqueous media but can generate significant singlet oxygen (O-1(2,) one of the reactive oxygen species, the real cytotoxic agent in photodynamic therapy) in living cells and exhibit high light cytotoxicity to three cancer cell lines. The mechanism studies indicated the mitochondrial localization of BODIPY3-PEG(3) was able to generate ROS in mitochondria, which further result in mitochondrial dysfunction and photoinduced apoptosis via caspase-8 and caspase-3 pathway. (C) 2018 Elsevier Masson SAS. All rights reserved.
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