Ruthenium-Based Photoactivated Chemotherapy

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(43), P. 23397 - 23415

Published: Oct. 17, 2023

Ruthenium(II) polypyridyl complexes form a vast family of molecules characterized by their finely tuned photochemical and photophysical properties. Their ability to undergo excited-state deactivation via photosubstitution reactions makes them quite unique in inorganic photochemistry. As consequence, they have been used, general, for building dynamic molecular systems responsive light but, more particularly, the field oncology, as prodrugs new cancer treatment modality called photoactivated chemotherapy (PACT). Indeed, coordination bond be selectively broken under visible irradiation offers fascinating perspectives oncology: it is possible make poorly toxic agents dark that become activated toward cell killing simple compound inside tumor. In this Perspective, we review most important concepts behind PACT idea, relationship between ruthenium compounds used those related phototherapeutic approach photodynamic therapy (PDT), discuss questions about real-life applications clinic. We conclude Perspective with challenges an outlook.

Language: Английский

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Targeting fatty acid synthase modulates sensitivity of hepatocellular carcinoma to sorafenib via ferroptosis

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Jan. 6, 2023

Sorafenib resistance is a key impediment to successful treatment of patients with advanced hepatocellular carcinoma (HCC) and recent studies have reported reversal drug by targeting ferroptosis. The present study aimed explore the association fatty acid synthase (FASN) sorafenib via regulation ferroptosis provide novel strategy overcome HCC patients.Intracellular levels lipid peroxides, glutathione, malondialdehyde, Fe2+ were measured as indicators status. Biological information analyses, immunofluorescence assays, western blot co-immunoprecipitation analyses conducted elucidate functions FASN in HCC. Both vitro vivo examine antitumor effects combination orlistat CalcuSyn software was used calculate index.Solute carrier family 7 member 11 (SLC7A11) found play an important role mediating resistance. up-regulation antagonize SLC7A11-mediated thereby promoted Mechanistically, enhanced sorafenib-induced binding hypoxia-inducible factor 1-alpha (HIF1α), promoting HIF1α nuclear translocation, inhibiting ubiquitination proteasomal degradation HIF1α, subsequently enhancing transcription SLC7A11. Orlistat, inhibitor FASN, had significant synergistic reversed both vivo.Targeting FASN/HIF1α/SLC7A11 pathway resensitized cells sorafenib. superior sorafenib-resistant cells.

Language: Английский

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Multimetallic transition metal complexes:Luminescent probes for biomolecule sensing, ion detection, imaging and therapeutic application

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 504, P. 215656 - 215656

Published: Jan. 19, 2024

Language: Английский

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Nanoparticle-mediated synergistic anticancer effect of ferroptosis and photodynamic therapy: novel insights and perspectives

Asian Journal of Pharmaceutical Sciences, Journal Year: 2023, Volume and Issue: 18(4), P. 100829 - 100829

Published: July 1, 2023

Current antitumor monotherapy has many limitations, highlighting the need for novel synergistic anticancer strategies. Ferroptosis is an iron-dependent form of nonapoptotic cell death that plays a pivotal regulatory role in tumorigenesis and treatment. Photodynamic therapy (PDT) causes irreversible chemical damage to target lesions widely used therapy. However, PDT's effectiveness usually hindered by several obstacles, such as hypoxia, excess glutathione (GSH), tumor resistance. improves efficacy PDT increasing oxygen reactive species (ROS) or reducing GSH levels, also enhances ferroptosis induction due ROS effect microenvironment (TME). Strategies based on nanoparticles (NPs) can subtly exploit potential synergy PDT. This review explores recent advances current challenges landscape underlying mechanisms regulating PDT, well nano delivery system-mediated activity. These include polymers, biomimetic materials, metal organic frameworks (MOFs), inorganics, carrier-free NPs. Finally, we highlight future perspectives this emerging paradigm targeted cancer therapies.

Language: Английский

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Understanding sorafenib-induced ferroptosis and resistance mechanisms: Implications for cancer therapy

European Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 955, P. 175913 - 175913

Published: July 17, 2023

Language: Английский

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From synergy to resistance: Navigating the complex relationship between sorafenib and ferroptosis in hepatocellular carcinoma

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 170, P. 116074 - 116074

Published: Dec. 25, 2023

Hepatocellular carcinoma (HCC) remains a major global health burden, and sorafenib, multi-kinase inhibitor, has shown effectiveness in the treatment of HCC is considered as first-line therapy for advanced HCC. However, response to sorafenib varies among patients, development drug resistance poses prevalent obstacle. Ferroptosis, newly characterized form cell death featured by iron-dependent lipid peroxidation, emerged critical player reaction The induction ferroptosis been augment anticancer benefits sorafenib. it also observed contribute resistance. This review presents comprehensive thorough analysis that elucidates intricate relationship between over recent years, aiming formulate effective therapeutic approaches liver cancer. Based on this exploration, we propose innovative strategies intended overcome via targeted modulation ferroptosis.

Language: Английский

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Synthesis of Sorafenib−Ruthenium Complexes, Investigation of Biological Activities and Applications in Drug Delivery Systems as an Anticancer Agent

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(6), P. 4463 - 4482

Published: March 12, 2024

Sorafenib, a multiple kinase inhibitor, is widely used as first-line treatment for hepatocellular carcinoma. However, there need more effective alternatives when sorafenib proves insufficient. In this study, we aimed to design structure that surpasses sorafenib's efficacy, leading us synthesize sorafenib–ruthenium complexes the first time and investigate their properties. Our results indicate exhibit superior epidermal growth factor receptor (EGFR) inhibition compared alone. Interestingly, among these complexes, Ru3S demonstrated high activity against various cancer cell lines including sorafenib-resistant HepG2 cells while exhibiting significantly lower cytotoxicity than in healthy lines. Further evaluation of cycle, apoptosis, antiangiogenic effects, molecular docking, dynamics studies revealed holds great potential drug candidate. Additionally, free was encapsulated into polymeric micelles M1, enhanced on observed. Collectively, findings position promising candidate EGFR warrant further exploration development purposes.

Language: Английский

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Cycloplatinated (II) Complex Based on Isoquinoline Alkaloid Elicits Ferritinophagy-Dependent Ferroptosis in Triple-Negative Breast Cancer Cells

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(8), P. 6738 - 6748

Published: March 25, 2024

The development and optimization of metal-based anticancer drugs with novel cytotoxic mechanisms have emerged as key strategies to overcome chemotherapeutic resistance side effects. Agents that simultaneously induce ferroptosis autophagic death received extensive attention potential modalities for cancer therapy. However, only a limited set or treatment can synergistically tumor cell death. In this work, we designed synthesized four new cycloplatinated (II) complexes harboring an isoquinoline alkaloid C

Language: Английский

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Targeting the regulation of iron homeostasis as a potential therapeutic strategy for nonalcoholic fatty liver disease

Metabolism, Journal Year: 2024, Volume and Issue: 157, P. 155953 - 155953

Published: June 15, 2024

Language: Английский

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A Photoisomerizable Zinc (II) Complex Inhibits Microtubule Polymerization for Photoactive Therapy

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(14)

Published: Feb. 7, 2023

The photoisomerization-induced cytotoxicity in photopharmacology provides a unique pathway for phototherapy because it is independent of endogenous oxygen. In this study, we developed biosafe photoisomerizable zinc(II) complex (Zn1), which releases its trans ligand (trans-L1) after being irradiated with blue light. This causes the to undergo photoisomerization and produce toxic cis product (cis-L1) generate singlet oxygen (1 O2 ). resulting series events caused impressive phototoxicity hypoxic A431 skin cancer cells, as well tumor model vivo. Interestingly, Zn1 was able inhibit microtubule polymerization, while still showing good biocompatibility biosafety novel strategy addressing oxygen-dependent limitation traditional photodynamic therapy.

Language: Английский

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