A Molecular Combination of Zinc(II) Phthalocyanine and Tamoxifen Derivative for Dual Targeting Photodynamic Therapy and Hormone Therapy

The
combination of photodynamic therapy and other cancer treatment
modalities is a promising strategy to enhance therapeutic efficacy
and reduce side effects. In this study, a tamoxifen–zinc­(II)
phthalocyanine conjugate linked by a triethylene glycol chain has
been synthesized and characterized. Having tamoxifen as the targeting
moiety, the conjugate shows high specific affinity to MCF-7 breast
cancer cells overexpressed estrogen receptors (ERs) and tumor tissues,
therefore leading to a cytotoxic effect in the dark due to the cytostatic
tamoxifen moiety, and a high photocytotoxicity due to the photosensitizing
phthalocyanine unit against the MCF-7 cancer cells. The high photodynamic
activity of the conjugate can be attributed to its high cellular uptake
and efficiency in generating intracellular reactive oxygen species.
Upon addition of exogenous 17β-estradiol as an ER inhibitor,
the cellular uptake and photocytotoxicity of the conjugate are reduced
significantly. As shown by confocal microscopy, the conjugate is preferentially
localized in the lysosomes of the MCF-7 cells.