Riding the metal wave: A review of the latest developments in metal-based anticancer agents

Coordination Chemistry Reviews, Год журнала: 2023, Номер 501, С. 215579 - 215579

Опубликована: Ноя. 28, 2023

Язык: Английский

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Dinuclear Dicationic Iridium Complexes for Highly Synergistic Photodynamic and Photothermal Therapy to Chemoresistant Cancer

Inorganic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

A series of dinuclear Ir(III) complexes have been constructed for enhanced photodynamic and photothermal therapy (PDT PTT) cisplatin-resistant non-small-cell lung cancer. They enter cells via caveolar endocytosis, target mitochondria but not nuclear, generate both singlet oxygen superoxide anion, release heat when exposed to infrared (IR) irradiation, thus inducing reactive species (ROS)-associated cell disruption thermal ablation. The IR-generated ROS can further activate caspases, triggering apoptosis. Additionally, the deplete intracellular glutathione, lead lipid peroxidation, induce ferroptosis. selected complex

Язык: Английский

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Advances in the Design of Photoactivatable Metallodrugs: Excited State Metallomics

Angewandte Chemie International Edition, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Abstract Photoactivatable metal complexes offer the prospect of novel drugs with low side effects and new mechanisms action to combat resistance current therapy. We highlight recent progress in design platinum, ruthenium, iridium, gold other transition complexes, especially for applications as anticancer anti‐infective agents. In particular, understanding excited state chemistry related identification bioactive species (excited metallomics/pharmacophores) is important. metallodrugs are classified here photocatalysts, photorelease agents ligand‐activated Their activation wavelengths, cellular action, experimental theoretical metallomics states photoproducts discussed explore strategies investigation photoactivatable metallodrugs. These have potential clinical Photodynamic Therapy (PDT), Photoactivated Chemotherapy (PACT) Photothermal (PTT).

Язык: Английский

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Systematic review on antibacterial photodynamic therapeutic effects of transition metals ruthenium and iridium complexes

Journal of Inorganic Biochemistry, Год журнала: 2024, Номер 255, С. 112523 - 112523

Опубликована: Март 11, 2024

Язык: Английский

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

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(27)

Опубликована: Апрель 24, 2024

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

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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Chemiluminescent transition metal complexes: Mechanisms and applications

Coordination Chemistry Reviews, Год журнала: 2025, Номер 530, С. 216495 - 216495

Опубликована: Фев. 5, 2025

Язык: Английский

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Optically Pure Double-Stranded Dinuclear Ir(III) Metallohelices Enabled Chirality-Induced Photodynamic Responses

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(27), С. 14766 - 14775

Опубликована: Июнь 27, 2023

Investigation on the interactions between enantiomers of chiral drugs and biomolecules can help precisely understand their biological behaviors in vivo provide insights into design new drugs. Herein, we designed synthesized a pair optically pure, cationic, double-stranded dinuclear Ir(III)-metallohelices (Λ2R4-H Δ2S4-H), dramatic enantiomer-dependent photodynamic therapy (PDT) responses were thoroughly studied vitro vivo. Compared to mononuclear enantiomeric or racemic [Ir(ppy)2(dppz)][PF6] (Λ-/Δ-Ir, rac-Ir) that with high dark toxicity low photocytotoxicity index (PI) values, both pure metallohelices displayed negligible while exhibiting very distinctive light upon irradiation. The PI value Λ2R4-H was approximately 428, however, Δ2S4-H significantly reached 63,966. Interestingly, only found migrate from mitochondria nucleus after Further proteomic analysis verified activated ATP-dependent migration process irradiation, subsequently inhibited activities nuclear proteins such as superoxide dismutase 1 (SOD1) eukaryotic translation initiation factor 5A (EIF5A) trigger accumulation anions downregulate mRNA splicing processes. Molecular docking simulations suggested pore complex NDC1 dominated process. This work presents kind Ir(III) metallohelices-based agent highest PDT efficacy, highlights importance metallohelices' chirality, provides inspirations for future helical metallodrugs.

Язык: Английский

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

Langmuir, Год журнала: 2024, Номер 40(23), С. 12226 - 12238

Опубликована: Май 30, 2024

We have red-shifted the light absorbance property of a Re(I)-tricarbonyl complex via distant conjugation ferrocene moiety and developed novel ReFctp, [Re(Fctp)(CO)3Cl], where Fctp = 4′-ferrocenyl-2,2′:6′,2″-terpyridine. ReFctp showed green to red absorption ability blue emission, indicating its potential for photodynamic therapy (PDT) application. The introduced ferrocene-based transitions, which lie at higher wavelength within PDT therapeutic window. time-dependent density functional theory excited state calculations revealed an efficient intersystem crossing is helpful PDT. elicited both type I II pathways reactive oxygen species (ROS) generation facilitated NADH (1,4-dihydro-nicotinamide adenine dinucleotide) oxidation upon exposure visible light. Importantly, effective penetration through layers clinically relevant 3D multicellular tumor spheroids localized primarily in mitochondria (Pearson's correlation coefficient, PCC 0.65) A549 cancer cells. produced more than 20 times phototoxicity (IC50 ∼1.5 μM) by inducing ROS altering mitochondrial membrane cells nonferrocene analogue Retp, [Re(CO)3(tp)Cl], tp 2,2′:6′,2″-terpyridine. induced apoptotic mode cell death with notable photocytotoxicity index (PI, PI IC50dark/IC50light) selectivity (SI, SI normal cell's IC50dark/cancer IC50light) range 25–33.

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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