title: pH- and Thiol-Responsive BODIPY-Based Photosensitizers for Targeted Photodynamic Therapy.
abstract: A diiodo distyryl boron dipyrromethene (BODIPY) core was conjugated to two ferrocenyl quenchers through acid-labile ketal and/or thiol-cleavable disulfide linkers, of which the fluorescence and photosensitizing properties were significantly quenched through a photoinduced electron-transfer process. The two symmetrical analogues that contained either the ketal or disulfide linkers could only be activated by a single stimulus, whereas the unsymmetrical analogue was responsive to dual stimuli. Upon interaction with acid and/or dithiothreitol (DTT), these linkers were cleaved selectively. The separation of the BODIPY core and the ferrocenyl moieties restored the photoactivities of the former in phosphate buffered saline and inside the MCF-7 breast cancer cells, rendering these compounds as potential activable photosensitizers for targeted photodynamic therapy. The dual activable analogue exhibited the greatest enhancement in intracellular fluorescence intensity in both an acidic environment (pH 5) and the presence of DTT (4 mm). Its photocytotoxicity against MCF-7 cells also increased by about twofold upon preincubation with 4 mm of DTT. The activation of this compound was also demonstrated in nude mice bearing a HT29 human colorectal carcinoma. A significant increase in fluorescence intensity in the tumor was observed over 9 h after intratumoral injection.
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, S.A.R. China.
authors.forename: Xiong-Jie
authors.initials: XJ
authors.lastname: Jiang
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, S.A.R. China.
authors.forename: Janet T F
authors.initials: JT
authors.lastname: Lau
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, S.A.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, S.A.R. China. dkpn@cuhk.edu.hk.
authors.forename: Dennis K P
authors.initials: DK
authors.lastname: Ng
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, S.A.R. China. gigi.lo@cityu.edu.hk.
authors.forename: Pui-Chi
authors.initials: PC
authors.lastname: Lo
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004229:Dithiothreitol / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008027:Light; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology; D061848:Optical Imaging; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013050:Spectrometry, Fluorescence; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D014183:Transplantation, Heterologous
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D017319:Photosensitizing Agents; D013438:Sulfhydryl Compounds; D004229:Dithiothreitol
keywords: cancer; imaging agents; photochemistry; photodynamic therapy; sensitizers