PH‐ and Thiol‐Responsive BODIPY‐Based Photosensitizers for Targeted Photodynamic Therapy1. Issue 24 (3rd May 2016)

• Record Type: Journal Article
• Authors: Jiang, Xiong‐Jie; Lau, Janet T. F.; Wang, Qiong; Ng, Dennis K. P.; Lo, Pui‐Chi
• Is Part Of: Chemistry. Volume 22:Issue 24(2016)
• Page Start: 8273
• Page End: 8281
• Publication Date: 2016-05-03
• Subjects: cancer -- imaging agents -- photochemistry -- photodynamic therapy -- sensitizers; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201600452
• Languages: English
• ISSNs: 0947-6539

Abstract

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. Abstract : Call to action : Three bisferrocenyl distyryl boron dipyrromethene (BODIPY) derivatives have been prepared, the photoactivities of which can be activated by acid and/or dithiothreitol (DTT) both in phosphate buffered saline and at the cellular level (see figure). The in vivo activation of the dual activatable analogue has also been demonstrated.