Estrogen-Functionalized Ru(II) Polypyridyl Complexes Self-Assemble into Aggregates and Exhibit Selective Phototoxicity against Breast Cancer Cells

TL;DR

Researchers developed a new type of light-activated cancer treatment using estrogen-linked Ru(II) complexes that selectively target breast cancer cells.

Contribution

Estrogen-functionalized Ru(II) complexes show selective phototoxicity against ER+ breast cancer cells, offering a new approach for targeted photodynamic therapy.

Findings

Estrogen-functionalized Ru(II) complexes self-assemble into micelle-like structures under biological conditions.

Two complexes exhibit up to 9.6-fold higher light-induced cytotoxicity toward ER+ compared to ER− breast cancer cells.

Aggregation of complexes enhances cellular uptake and phototoxic effects in targeted cancer cells.

Abstract

Photodynamic therapy (PDT) constitutes a promising cancer
treatment
modality in which an administered photosensitizer is excited with
visible light to induce the localized generation of cytotoxic reactive
oxygen species (ROS) at the tumor site, thus minimizing damage to
healthy tissues and avoiding the use of ionizing radiation. However,
most photosensitizers lack inherent selectivity for cancer cells,
leading to undesirable accumulation in healthy tissues. The readily
formed triplet excited states of Ru­(II) polypyridyl complexes, coupled
with their kinetic inertness, make them suitable candidates as photosensitizers
for PDT. Herein, we report the synthesis of a series of estrogen-functionalized
Ru­(II) complexes using click chemistry and investigate their photophysical
properties and biological activity. Dynamic light scattering studies,
supported by time-resolved luminescence studies, indicate that the
complexes self-assemble into micelle-like structures under experimental
conditions relevant to biological studies. Our findings reveal that
two of these complexes exhibit highly selective light-induced cytotoxicity
toward ER+ breast cancer cells compared to estrogen receptor-negative
(ER−) cells, by a factor of up to 9.6. Overall, this study
highlights the potential of estrogen-conjugated Ru­(II) complexes for
targeted PDT, as well as the importance of aggregation in enhancing
cellular uptake.

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