Heterometallic ruthenium–osmium complexes: dual photodynamic and photothermal therapy for melanoma and drug-resistant lung tumour<i>in vivo</i>

Deng, Yu-Ang; Tang, Shi‐Jie; Wang, Mengfan; Ren, Xiaoxia; Li, Xuelian; Zeng, Lixuan; Ren, Dan‐ni; Wang, Meng-Ru; Xiao, Wei‐Lie; Cai, Zheng; Zhang, Dan; Zhang, Hongbin; Gao, Feng

doi:10.1039/d3qi00903c

Cited by 7 publications

(3 citation statements)

References 30 publications

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“…The Φ Δ808 values of Ir(III)-PSs are quite remarkable (0.03–0.13), in comparison to [Ru(bpy) 3 ] 2+ (0.006), a series of dinuclear and mononuclear homoligand Ru(II)-PSs (0.020–0.156), heterocyclic containing Ir(III)-PSs (0.026–0.110), and Ru(II)–Os(II) heteronuclear PSs (0.06–0.32) under identical experimental conditions. Interestingly, the Φ Δ808 values of Ir(III)-PSs exhibited an ignorable correlation with Φ Δ400 but more consistent with the regularity of σ 808 .…”

Section: Resultsmentioning

confidence: 97%

“…Moreover, the complete coverage of solid tumors by the highly concentrated laser beam is severely limited, thereby significantly constraining its practicality. We have achieved successful dual TP-PDT and PTT through the utilization of a combination of a low-power laser (LPL, 808 nm, 100 mW cm –2 ) with an adjustable spot-size (beam diameter >1.0 cm) as a light source and single-molecule Ru(II), Os(II), and Ir(III) complexes with extremely high TP absorption cross sections (TPACS) as both PSs and photothermal agents (PTAs). − The determination of photodynamic and photothermal properties is highly dependent on the allocation of excited state (ES) energy among various relaxation pathways, including radiative decay (luminescence), non-radiative (heat release), and energy transfer to oxygen (resulting in the production of 1 O 2 ).…”

Section: Introductionmentioning

confidence: 99%

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Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy

Li,

Zeng,

Yang

et al. 2023

Inorg. Chem.

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Cyclometalated iridium(III) complexes are of significant importance in the field of antitumor photodynamic therapy (PDT), whether they exist as single molecules or are incorporated into nanomaterials. Nevertheless, a comprehensive examination of the relationship between their molecular structure and PDT effectiveness remains awaited. The influencing factors of two-photon excited PDT can be anticipated to be further multiplied, particularly in relation to intricate nonlinear optical properties. At present, a comprehensive body of research on this topic is lacking, and few discernible patterns have been identified. In this study, through systematic structure regulation, the nitro-substituted styryl group and 1-phenylisoquinoline ligand containing YQ2 was found to be the most potent infrared two-photon excitable photosensitizer in a 4 × 3 combination library of cyclometalated Ir(III) complexes. YQ2 could enter cells via an energy-dependent and caveolae-mediated pathway, bind specifically to mitochondria, produce 1O2 in response to 808 nm LPL irradiation, activate caspases, and induce apoptosis. In vitro, YQ2 displayed a remarkable phototherapy index for both malignant melanoma (>885) and non-small-cell lung cancer (>1234) based on these functions and was minimally deleterious to human normal liver and kidney cells. In in vivo antitumor phototherapy, YQ2 inhibited tumor growth by an impressive 85% and could be eliminated from the bodies of mice with a half-life as short as 43 h. This study has the potential to contribute significantly to the development of phototherapeutic drugs that are extremely effective in treating large, profoundly located solid tumors as well as the understanding of the structure–activity relationship of Ir(III)-based PSs in PDT.

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Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy

Li,

Zeng,

Yang

et al. 2023

Inorg. Chem.

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“…Ru(II) DNA intercalators, represented by [Ru(bpy) 2 (dppz)] 2+ ( DZ , bpy = 2,2′-bipyridine; dppz = dipyrido[3,2- a :2′,3′- c ]phenazine; Figure a) and [Ru(bpy) 2 (pip)] 2+ (pip = 2-(phenyl)imidazo[4,5- f ][1,10]phenanthroline), have long been employed in DNA light switches, nucleic acid-related fluorescence probes, enzyme inhibitors, and antibacterial and antitumor agents. − Their antitumor mechanisms involve traditional chemotherapy and novel therapy including photodynamic, photothermal, chemodynamic, photoactivated chemotherapy, and immunogenic cell death, either alone or in combination. − However, research on Ru(II)-based antiviral agents is very rare. − …”

Section: Introductionmentioning

confidence: 99%

From Intercalation to External Binding: Ru(II) Complexes with a Spiro Ligand for TAR RNA Selective Binding and HIV-1 Reverse Transcriptase Inhibition

Xie,

Song,

Cheng

et al. 2024

Inorg. Chem.

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Bithiophene‐Functionalized Infrared Two‐Photon Absorption Metal Complexes as Single‐Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy

Li,

Wang,

Zeng

et al. 2024

Angewandte Chemie

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A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single‐molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two‐photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA‐related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin‐resistant non‐small cell lung cancer tumors, with a 100% survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two‐photon activatable metal complex may contribute to a new generation of single‐molecule‐based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.

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Heterometallic ruthenium–osmium complexes: dual photodynamic and photothermal therapy for melanoma and drug-resistant lung tumourin vivo

Abstract: A series of hetero-dinuclear Ru-Os complexes have been constructed by combining mononuclear modules derived from homo-dinuclear Ru-Ru complexes with dual PDT/PTT activity and Os-Os complexes with significant PTT activity but...

Cited by 7 publications

References 30 publications

Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy

Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy

From Intercalation to External Binding: Ru(II) Complexes with a Spiro Ligand for TAR RNA Selective Binding and HIV-1 Reverse Transcriptase Inhibition

Bithiophene‐Functionalized Infrared Two‐Photon Absorption Metal Complexes as Single‐Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy

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