Mitochondria-targeting hemicyanine photosensitizer as an inducer for MMP loss and cell apoptosis based on radical enhanced ISC strategy

Abstract

Hemicyanine dyes are known as widely used fluorophores with good biocompatibility and excellent photophysical property, but poor ability to produce singlet oxygen has limited their application in photodynamic therapy (PDT). Introduction of heavy atoms seems to be a feasible way to enhance the PDT efficiency, but undesired toxicity is inevitable. Herein, a radical enhanced intersystem crossing-based hemicyanine dye Cy-OT is synthesized and successfully applied in PDT process. The singlet oxygen quantum yield of Cy-OT increases by 4.2 times through the introduction of 4-hydroxyl-2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) unit. Cell experiments carried out in MCF-7 cells demonstrates that Cy-OT is localized in mitochondria and can produce single oxygen under the irradiation of 660 nm light which subsequently results in mitochondria membrane potential (MMP) loss and induces cell apoptosis. The therapeutic experiment of 4T1 tumor bearing mice further indicates that Cy-OT can serve as an ideal photosensitizer with good antitumor effect and negligible side effect to normal tissues.