A 700 nm LED Light Activated Ru(II) Complex Destroys Tumor Cytoskeleton via Photosensitization and Photocatalysis

Abstract

Photoactivable chemotherapy (PACT) using metallic complexes provides spatiotemporal selectivity over drug activation for targeted anticancer therapy. However, the poor absorption in near‐infrared (NIR) light region of most metallic complexes renders tissue penetration challenging. Herein, we present an NIR light triggered di‐nuclear photoactivable Ru(II) complex (Ru2) and comprehensively investigated the antitumor mechanism. The introduction of a donor‐acceptor‐donor (D‐A‐D) linker greatly enhances the intramolecular charge transition, resulting in a high molar extinction coefficient in the NIR region with an extended triplet excited state lifetime. Most importantly, when activated by 700 nm NIR light, Ru2 exhibits unique slow photodissociation kinetics that facilitates synergistic photosensitization and photocatalytic activity to destroy diverse intracellular biomolecules. In vitro and in vivo experiments show that when activated by 700 nm NIR light, Ru2 exhibits nanomolar photocytotoxicity toward 4T1 cancer cells via the induction of calcium overload and endoplasmic reticulum (ER) stress. These findings provide a robust foundation for the development of NIR‐activated Ru(II) PACT complexes for phototherapeutic application.This article is protected by copyright. All rights reserved

New cyclometalated Ru(ii) polypyridyl photosensitizers trigger oncosis in cancer cells by inducing damage to cellular membranes

“…We also investigated the ability of the new compounds to produce hydroxyl radical OH • , a specific type-I ROS that could provide the potential to inhibit hypoxic tumor cells, in PBS (5% DMF) by using a spectroscopic method based on the oxidation of the non-fluorescent 3′-p-(hydroxyphenyl)fluorescein (HPF) probe by OH • to the corresponding fluorescent product. 35,36 As shown in Fig. 5B and Fig.…”

Donor–Acceptor–Donor Strategy Rouses the Photodynamic Therapy Anticancer Activity of a Bis-terpyridyl Ru(II) Complex

“…To improve the 3 ES reactivity and PDT activity of bis-tridentate Ru(II) complexes, Turro et al, Glazer et al, and Chakravarty et al developed several effective tridentate ligand frameworks. − However, most of the reported bis-tridentate Ru(II) PSs should be excited by short wavelength visible light, limiting the tissue penetration depth. Recently, Schanze et al, Sun et al, Gou et al, Zhang et al., and our group used donor–acceptor–donor (D-A-D) chromophores to extend light absorption wavelength and promote the electron transfer property of tris-bidentate metal complexes. − However, the potent efficiency of the D-A-D strategy for the 3 ES reactivity of the bis-terpyridyl Ru(II) complex still needs to be investigated.…”