Comparative Study of Sonodynamic and Photoactivated Cancer Therapies with Re(I)-Tricarbonyl Complexes Comprising Phenanthroline Ligands

Abstract

Herein, we have compared the effectivity of lightbased photoactivated cancer therapy and ultrasound-based sonodynamic therapy with Re(I)-tricarbonyl complexes (Re1− Re3) against cancer cells. The observed photophysical and TD-DFT calculations indicated the potential of Re1−Re3 to act as good anticancer agents under visible light/ultrasound exposure. Re1 did not display any dark-or light-or ultrasound-triggered anticancer activity. However, Re2 and Re3 displayed concentration-dependent anticancer activity upon light and ultrasound exposure. Interestingly, Re3 produced 1 O 2 and OH • on light/ ultrasound exposure. Moreover, Re3 induced NADH photooxidation in PBS and produced H 2 O 2 . To the best of our knowledge, NADH photo-oxidation has been achieved here with the Re(I) complex for the first time in PBS. Additionally, Re3 released CO upon light/ultrasound exposure. The cell death mechanism revealed that Re3 produced an apoptotic cell death response in HeLa cells via ROS generation. Interestingly, Re3 showed slightly better anticancer activity under light exposure compared to ultrasound exposure.

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

“…In addition, both NADH and NADPH are important reductants of the oxidative damage defense system . Previously, we and others have reported metal complexes catalytically oxidized NADH or NADPH for light-triggered multitarget photocatalytic anticancer therapy. ,− In the case of Ru2 , remarkable NADH/NAD(P)H oxidation (Figure d and Figures S18–S20) was observed with turnover frequency (TOF) reaching 2117/2525 h –1 (Tables S2 and S3), respectively. Importantly, the TOFs of Ru2 were much higher than metal-based photocatalysts reported previously. ,, Moreover, this was the first report of the dinuclear bis-terpyridyl Ru(II) complex for effective photocatalytic NADH/NADPH oxidation.…”

“…Photodynamic therapy (PDT), with promising spatiotemporal control over drug activation property, has been regarded as a noninvasive treatment for cancer. − PDT utilizes light to excite a photosensitizer (PS) from the ground state to the triplet excited state ( 3 ES), which subsequently interacts with oxygen to generate reactive oxygen species (ROS) and kill cancer cells . In general, a promising PS requires efficient intersystem crossing (ISC) and a long 3 ES lifetime to facilitate electron transfer to generate oxygen radicals (type I pathway) or energy transfer to generate singlet oxygen ( 1 O 2 , type II pathway). − More recently, we and others have taken advantage of the 3 ES redox potential of metal complexes and developed photocatalytic therapy via catalyzing the electron transfer between coenzymes (NADH/NAD(P)H) and subtracts. − Elimination of coenzymes may affect the biosynthetic or metabolic process of cancer cells, which can enhance the PDT activity under hypoxia . Thus, 3 ES reactivity is highly important for PDT, but novel PSs are still to be discovered. , …”

Visible and Red Light-Triggered Anticancer Profile of a Ferrocene-Re(I)-Tricarbonyl Conjugate: Experimental and Theoretical Studies

“…Under red light, ReFctp exhibited an IC 50 value of ∼5.4 μM against the A549 cell line (Table ). This result is of high significance, indicating that deeply buried tumors can be treated with ReFctp using the high tissue penetration depth of the red light . Moreover, this observation will enable us to study this complex as red light photochemotherapeutics in vivo .…”