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 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.