Optical and random laser properties of the novel multifunctional endoxifen derivative (FLTX3) and its potential for the diagnosis of breast cancer resistance.

Endoxifen is the most powerful metabolite of tamoxifen (TX), the main endocrine therapy administered worldwide for the treatment of estrogen-receptor (ER) positive metastatic breast cancer. Tamoxifen itself is a prodrug with weak affinity for ER, but it is converted into endoxifen, with up to 100-fold higher affinity for ER than TX. In this study, we introduce the first fluorescent endoxifen derivative (FLTX3), formed by covalent attachment of the small fluorophore NBD to the basic side chain of endoxifen. We have characterized the optical properties of FLTX3, demonstrating its ability as a laser dye. FLTX3 is an efficient target-directed fluorescent probe for the cellular labelling of ER in MCF7 breast cancer cell line as well as in uterine tissues. FLTX3 is also endowed with an intrinsic photodynamic effect when irradiated at the optimal excitation wavelength of FLTX3. Further, we show that FLTX3 has an optical gain behaviour that leads to random laser (RL) when the light emitted by the drug is scattered in the cell cultures. Indeed, analyses of coherent spectra by power function Fourier transform revealed a RL dominant cavity in the range of average cell sizes. As one of the main causes for tamoxifen treatment failure is resistance, we explored the potential discriminative value of FLTX3-induced RL between tamoxifen-resistant and tamoxifen-sensitive MCF7 cells. Using multivariate approaches, we unravelled significant differences in the RL signal between tamoxifen-sensitive and tamoxifen-resistant cells. These findings indicate that FLTX3-generated RL might provide a target-directed diagnostic tool for tamoxifen resistance in metastatic ER+ breast cancer.