FRET mechanism between a fluorescent breast-cancer drug and photodynamic therapy sensitizers

Tamoxifen is one of the most frequently used drugs for the treatment of estrogen receptor positive breast cancer, which is the most prevalent form of hormone dependent breast cancer. A few years ago, we developed a fluorescent derivative of tamoxifen formed by the covalent binding of tamoxifen to a common dye biomarker. The new compound, known as FLTX1, showed the pharmacological activity of the tamoxifen moiety and efficient fluorescence properties, which could be used synergistically to improve the effect of the drug. In this paper, we demonstrate that irradiation at the absorption band of FLTX1 can result in fluorescence resonance energy transfer to photosensitizers such as Rose Bengal and Merocyanine 540, activating the production of reactive oxygen species (ROS). Indeed, the generation of ROS was demonstrated using a colorimetric assay. Since FLTX1 mostly binds estrogen-receptor overexpressing cancer cells, the results obtained are very promising and suggest a new therapeutic strategy combining chemo- and photodynamic therapies.