Ru(II) Oligothienyl Complexes with Fluorinated Ligands: Photophysical, Electrochemical, and Photobiological Properties

Inorganic Chemistry, Год журнала: 2024, Номер 63(21), С. 9735 - 9752

Опубликована: Май 10, 2024

A series of Ru(II) complexes incorporating two 4,4'-bis(trifluoromethyl)-2,2'-bipyridine (4,4'-btfmb) coligands and thienyl-appended imidazo[4,5-

Язык: Английский

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Uridine-Modified Ruthenium(II) Complex as Lysosomal LIMP-2 Targeting Photodynamic Therapy Photosensitizer for the Treatment of Triple-Negative Breast Cancer

JACS Au, Год журнала: 2024, Номер 4(3), С. 1081 - 1096

Опубликована: Фев. 16, 2024

Lysosome-targeted photodynamic therapy, which enhances reactive oxygen species (ROS)-responsive tumor cell death, has emerged as a promising strategy for cancer treatment. Herein, uridine (dU)-modified Ru(II) complex (RdU) was synthesized by click chemistry. It found that RdU exhibits impressive photo-induced inhibition against the growth of triple-negative breast (TNBC) cells in normoxic and hypoxic microenvironments through ROS production. further revealed induces ferroptosis MDA-MB-231 under light irradiation (650 nm, 300 mW/cm2). Additional experiments showed binds to lysosomal integral membrane protein 2 (LIMP-2), confirmed fact selectively localizes lysosomes significantly augments levels LIMP-2. Molecular docking simulations an isothermal titration calorimetry assay also high affinity Finally, vivo studies tumor-bearing (MDA-MB-231 cells) nude mice exerts therapeutic effects on TNBC tumors. In summary, uridine-modified been developed potential LIMP-2 targeting agent treatment enhancing production promoting ferroptosis.

Язык: Английский

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Chiral Iridium-Based TLD-1433 Analogues: Exploration of Enantiomer-Dependent Behavior in Photodynamic Cancer Therapy

Inorganic Chemistry, Год журнала: 2024, Номер 63(17), С. 7792 - 7798

Опубликована: Апрель 15, 2024

Metallodrug-based photodynamic therapy (PDT) agents have demonstrated significant superiority against cancers, while their different chirality-induced biological activities remain largely unexplored. In this work, we successfully developed a pair of enantiopure mononuclear Ir(III)-based TLD-1433 analogues, Δ-Ir-3T and Λ-Ir-3T, enantiomer-dependent anticancer behaviors were investigated. Photophysical measurements revealed that they display high photostability chemical stability, strong absorption at 400 nm with molar extinction coefficients (ε = 5.03 × 104 M–1 cm–1), good 1O2 relative quantum yields (ΦΔ ≈ 47%). Δ- Λ-Ir-3T showed potent efficacy MCF-7 cancer cells, photocytotoxicity index ≤44 238. This impressive result, to the best our knowledge, represents highest value among reported PDT agents. Remarkably, tended be more than when tested SK-MEL-28, HepG2, LO2 consistent results across multiple test repetitions.

Язык: Английский

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Ruthenium(II) Polypyridyl Complexes Containing COUBPY Ligands as Potent Photosensitizers for the Efficient Phototherapy of Hypoxic Tumors

Journal of the American Chemical Society, Год журнала: 2025, Номер 147(9), С. 7360 - 7376

Опубликована: Фев. 15, 2025

Hypoxia, a hallmark of many solid tumors, is linked to increased cancer aggressiveness, metastasis, and resistance conventional therapies, leading poor patient outcomes. This challenges the efficiency photodynamic therapy (PDT), which relies on generation cytotoxic reactive oxygen species (ROS) through irradiation photosensitizer (PS), process partially dependent levels. In this work, we introduce novel family potent PSs based ruthenium(II) polypyridyl complexes with 2,2′-bipyridyl ligands derived from COUPY coumarins, termed COUBPYs. Ru-COUBPY exhibit outstanding in vitro cytotoxicity against CT-26 cells when irradiated light within phototherapeutic window, achieving nanomolar potency both normoxic hypoxic conditions while remaining nontoxic dark, impressive phototoxic indices (>30,000). Their ability generate Type I II ROS underpins their exceptional PDT efficiency. The lead compound study, SCV49, shows favorable vivo pharmacokinetic profile, excellent toxicological tolerability, tumor growth inhibition mice bearing subcutaneous tumors at doses as low 3 mg/kg upon deep-red (660 nm). These results allow us propose SCV49 strong candidate for further preclinical development, particularly treating large tumors.

Язык: Английский

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Novel 2-(5-Arylthiophen-2-yl)-benzoazole Cyclometalated Iridium(III) dppz Complexes Exhibit Selective Phototoxicity in Cancer Cells by Lysosomal Damage and Oncosis

Journal of Medicinal Chemistry, Год журнала: 2023, Номер 67(1), С. 691 - 708

Опубликована: Дек. 23, 2023

A second-generation series of biscyclometalated 2-(5-aryl-thienyl)-benzimidazole and -benzothiazole Ir(III) dppz complexes [Ir(C^N)2(dppz)]+, Ir1–Ir4, were rationally designed synthesized, where the aryl group attached to thienyl ring was p-CF3C6H4 or p-Me2NC6H4. These new assessed as photosensitizers explore structure–activity correlations for their potential use in biocompatible anticancer photodynamic therapy. When irradiated with blue light, exhibited high selective potency across several cancer cell lines predisposed therapy; benzothiazole derivatives (Ir1 Ir2) best performers, Ir2 being also activatable green red light. Notably, when irradiated, induced leakage lysosomal content into cytoplasm HeLa cells oncosis-like death. The capability Ir photoinduce death 3D spheroids has been demonstrated. investigated can catalytically photo-oxidate NADH photogenerate 1O2 and/or •OH cell-free media.

Язык: Английский

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Ru(II) Phenanthroline-Based Oligothienyl Complexes as Phototherapy Agents

Inorganic Chemistry, Год журнала: 2023, Номер 62(51), С. 21181 - 21200

Опубликована: Дек. 11, 2023

Ru(II) polypyridyl complexes have gained widespread attention as photosensitizers for photodynamic therapy (PDT). Herein, we systematically investigate a series of the type [Ru(phen)2(IP-nT)]2+, featuring 1,10-phenanthroline (phen) coligands and imidazo[4,5-f][1,10]phenanthroline ligands tethered to n = 0-4 thiophene rings (IP-nT). The were characterized investigated their electrochemical, spectroscopic, (photo)biological properties. electrochemical oxidation nT unit shifted by -350 mV 1 → 4 (+920 Ru-1T, +570 Ru-4T); reductions observed in Ru-3T (-2530 mV) Ru-4T (-2300 mV). Singlet oxygen quantum yields ranged from 0.53 0.88, with being equally efficient (∼0.88). Time-resolved absorption spectra Ru-0T-1T dominated metal-to-ligand charge-transfer (3MLCT) states (τTA 0.40-0.85 μs), but long-lived intraligand (3ILCT) Ru-2T-4T 25-148 μs). 3ILCT energies computed be 1.6 1.4 eV, respectively. phototherapeutic efficacy against melanoma cells (SK-MEL-28) under broad-band visible light (400-700 nm) increases 0 4: Ru-0T was inactive up 300 μM, Ru-1T-2T moderately active (EC50 ∼ 600 nM, PI 200), 57 > 1100) 740 pM, 114,000) most phototoxic. activity diminishes longer wavelengths is completely suppressed all except hypoxia. more potent robust PS 1% O2 over seven biological replicates (avg EC50 1.3 avg 985). exhibited hypoxic five replicates, underscoring need compound evaluation. sensitization likely responsible phototoxic effects compounds normoxia, presence redox-active excited may facilitate additional photoactive pathways three or thienyl groups. state its extended lifetime (30-40× than 3MLCT Ru-4T) implicates predominant role photocytotoxicity.

Язык: Английский

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Light-driven sextuple theranostics: nanomedicine involving second near-infrared AIE-active Ir(III) complex for prominent cancer treatment

Science China Chemistry, Год журнала: 2024, Номер 67(7), С. 2314 - 2324

Опубликована: Июнь 11, 2024

Язык: Английский

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Leveraging the Photofunctions of Transition Metal Complexes for the Design of Innovative Phototherapeutics

Small Methods, Год журнала: 2024, Номер 8(11)

Опубликована: Сен. 25, 2024

Abstract Despite the advent of various medical interventions for cancer treatment, disease continues to pose a formidable global health challenge, necessitating development new therapeutic approaches more effective treatment outcomes. Photodynamic therapy (PDT), which utilizes light activate photosensitizer produce cytotoxic reactive oxygen species (ROS) eradicating cells, has emerged as promising approach due its high spatiotemporal precision and minimal invasiveness. However, widespread clinical use PDT faces several challenges, including inefficient production ROS in hypoxic tumor microenvironment, limited penetration depth biological tissues, inadequate accumulation photosensitizers at site. Over past decade, there been increasing interest utilization photofunctional transition metal complexes applications their intriguing photophysical photochemical properties. This review provides an overview current design strategies used innovative phototherapeutics, aiming address limitations associated with achieve The challenges future perspectives on translation are also discussed.

Язык: Английский

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More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy

Inorganic Chemistry, Год журнала: 2023, Номер 62(21), С. 8210 - 8218

Опубликована: Май 17, 2023

Photodynamic therapy (PDT) uses a combination of photosensitizers (PSs), light sources, and reactive oxygen species (ROS) to damage only the desired target keep normal tissues from being hurt. The dark cytotoxicity (chemotoxicity) PSs, leading whole-body in absence irradiation, is major limiting factor PDT. How simultaneously increase ROS generation decrease an essential challenge that must be resolved PS research. In this study, series homoligand polypyridyl ruthenium complexes (HPRCs) containing three singlet (1O2)-generating ligands (L) single molecule ([Ru(L)3]2+) have been constructed. Compared heteroligand [Ru(bpy)2(L)]2+ where bpy 2,2'-bipyridine, 1O2 quantum yield under infrared two-photon irradiation DNA photocleavage effect HPRCs are significantly enhanced with two more L. intraligand triplet excited states transition played important role activation oxygen. mitochondria but not nuclei, generating intracellularly visible or light. Ru1 exhibits high phototoxicity low toward human malignant melanoma cells vitro. Moreover, minimal liver cells, suggesting their potential as antitumor PDT reagents security. This study may provide inspiration for structural design potent

Язык: Английский

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Multiple Triplet Metal‐Centered Jahn‐Teller Isomers Determine Temperature‐Dependent Luminescence Lifetimes in [Ru(bpy)₃]²⁺

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(48)

Опубликована: Июль 12, 2023

Abstract Understanding the factors that determine luminescence lifetime of transition metal compounds is key for applications in photocatalysis and photodynamic therapy. Here we show (bpy = 2,2’‐bipyridine), generally accepted idea emission lifetimes can be controlled optimizing energy barrier from emissive triplet metal‐to‐ligand charge‐transfer ( 3 MLCT) state to thermally‐activated metal‐centered MC) or gap between both states a misconception. Further, demonstrate considering single relaxation pathway determined minimum lowest leads wrong temperature‐dependent predictions. Instead, obtain excellent agreement with experimental when an extended kinetic model includes all pathways related multiple Jahn–Teller isomers their effective reaction barriers employed. These concepts are essential correctly design other luminescent complexes tailored based on theoretical

Язык: Английский

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