A hydrogen peroxide responsive resorufin-based phototheranostic agent for selective treatment of cancer cells. (September 2021)

• Record Type: Journal Article
• Authors: Almammadov, Toghrul; Kolemen, Safacan
• Is Part Of: Dyes and pigments. Volume 193(2021)
• Publication Date: 2021-09
• Subjects: Cancer -- Photodynamic therapy -- Resorufin -- Photosensitizers -- Theranostic -- Hydrogen peroxide; Dyes and dyeing -- Periodicals; Pigments -- Periodicals; 667.2
• DOI: 10.1016/j.dyepig.2021.109499
• Languages: English
• ISSNs: 0143-7208

Abstract

Abstract: Enhanced selectivity towards cancer cells is one of the most essential features sought in new generation photodynamic therapy (PDT) agents in order to minimize the side effects on healthy cells and to improve the efficacy of the treatment. In this direction, one promising approach is to design activatable photosensitizers, which tend to stay in an OFF state and get activated only in cancer cells with tumor-associated stimuli. Based on this idea, herein we introduced a hydrogen peroxide (H2 O2 ) activatable iodinated resorufin (RR-1) as a red-shifted, water soluble and cancer cell selective photosensitizer. RR-1 exhibited high singlet oxygen quantum yield in aqueous solutions upon reacting with H2 O2 and induced selective photocytotoxicity in colorectal (HCT-116) and triple negative breast (MDA MB-231) cancer cells, which contain high level of reactive oxygen species (ROS). Additionally, fluorescence signal of the iodo-resorufin core was restored upon cleavage of the cage unit in these cancer cells. In contrast, very low photocytotoxicity and negligible fluorescence enhancement were observed in normal fibroblast (NIH-3T3) cells. RR-1 not only marks the first example of a H2 O2 activatable resorufin-based photosensitizer but also represents the first ever resorufin-based theranostic agent. We anticipate that iodo-resorufin scaffold can be easily modified with different masking units towards realization of highly selective and efficient phototheranostic agents for treatment of various cancer cells. Graphical abstract: Image 1 Highlights: A hydrogen peroxide activatable phototheranostic agent (RR-1) was developed. RR-1 marks the first ever example of a resorufin-based theranostic agent. RR-1 exhibited high singlet oxygen generation yields in aqueous solutions. Selective photocytotoxicity and turn-on fluorescence response on cancerous HCT-116 and MDA MB-231 cells were obtained. RR-1 stayed inactive in normal (NIH-3T3) cells.