A Green-Absorbing, Red-Fluorescent Phenalenone-Based Photosensitizer as a Theranostic Agent for Photodynamic Therapy

Phenalenone is a synthetically accessible, highly efficient photosensitizer with a near-unity singlet oxygen quantum yield. Unfortunately, its UV absorption and lack of fluorescence has made it unsuitable for fluorescence-guided photodynamic therapy against cancer. In this work, we synthesized a ser...

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Bibliographic Details
Published in:ACS medicinal chemistry letters 2021-08, Vol.12 (8), p.1295-1301
Main Authors: Kaye, Esther G, Kailass, Karishma, Sadovski, Oleg, Beharry, Andrew A
Format: Article
Language:English
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Letter
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Summary:Phenalenone is a synthetically accessible, highly efficient photosensitizer with a near-unity singlet oxygen quantum yield. Unfortunately, its UV absorption and lack of fluorescence has made it unsuitable for fluorescence-guided photodynamic therapy against cancer. In this work, we synthesized a series of phenalenone derivatives containing electron-donating groups to red-shift the absorption spectrum and bromine(s) to permit good singlet oxygen production via the heavy-atom effect. Of the derivatives synthesized, the phenalenone containing an amine at the 6-position with bromines at the 2- and 5-positions (OE19) exhibited the longest absorption wavelength (i.e., green) and produced both singlet oxygen and red fluorescence efficiently. OE19 induced photocytotoxicity with nanomolar potency in 2D cultured PANC-1 cancer cells as well as light-induced destruction of PANC-1 spheroids with minimal dark toxicity. Overall, OE19 opens up the possibility of employing phenalenone-based photosensitizers as theranostic agents for photodynamic cancer therapy.
ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.1c00284