Advances in Ferroptosis Research: A Comprehensive Review of Mechanism Exploration, Drug Development, and Disease Treatment

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(3), P. 334 - 334

Published: Feb. 26, 2025

In recent years, ferroptosis, as an emerging modality of programmed cell death, has captured significant attention within the scientific community. This comprehensive review meticulously canvasses pertinent literature past few spanning multiple facets. It delves into intricate mechanisms underpinning tracks evolution its inducers and inhibitors, dissects roles in a diverse array diseases, well resultant therapeutic implications. A profound exploration is conducted functional ferroptosis-related molecules, intracellular pathways, metabolic cascades, signaling transduction routes. Novel ferroptosis inhibitors are introduced detail, covering their design blueprints, synthetic methodologies, bioactivity profiles. Moreover, exhaustive account provided regarding involvement malignancies, neurodegenerative disorders, cardiovascular ailments, other pathologies. By highlighting pivotal status potential regimens various this aspires to furnish thorough reference framework for future investigations clinical translations domain.

Language: Английский

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A novel silkworm excrement-derived nanomedicine integrating ferroptosis and photodynamic therapy, well-suitable for PD-L1-mediated immune checkpoint blockade

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: 505, P. 159676 - 159676

Published: Jan. 17, 2025

Language: Английский

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Development of a Highly Selective Ferroptosis Inducer Targeting GPX4 with 2-Ethynylthiazole-4-carboxamide as Electrophilic Warhead

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 68(3), P. 3309 - 3323

Published: Jan. 30, 2025

A highly selective ferroptosis inducer with drug-like properties can significantly advance the research on inducing for anticancer treatment. We previously reported a active GPX4 inhibitor 26a, but its activity and stability need further improvement. In this work, novel (R)-9i more potent cytotoxicity (IC50 = 0.0003 μM against HT1080) selectivity (selectivity index 24933) was gained via electrophilic warhead screening structure-based optimization. The cellular thermal shift assay (CETSA) indicated that could stabilize Tm value of 6.2 °C. Furthermore, showed strong binding affinity (KD 20.4 nM). More importantly, has favorable pharmacokinetic than which endowed potential in antitumor as tool drug study ferroptosis. Associated these, treatment inhibited tumor growth xenograft mouse model without detectable toxicity.

Language: Английский

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Design, Synthesis, and Biological Evaluation of RSL3-based GPX4 Degraders with Hydrophobic Tags

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 277, P. 116719 - 116719

Published: July 27, 2024

Language: Английский

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Electron-reservoir applications of ferrocenes and other late transition-metal sandwich complexes: Flow batteries, sensing, catalysis, and biomedicine

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 524, P. 216300 - 216300

Published: Nov. 9, 2024

Language: Английский

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Synthesis and Bio-evaluation of Aminoferrocene-Based Anticancer Prodrugs as Potent Ferroptosis Inducers

Inorganic Chemistry Frontiers, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Novel ROS-responsive N -alkylaminoferrocene (NAAF)-appended GPX4 inhibitors have been designed and prepared as potent ferroptosis-inducing prodrugs.

Language: Английский

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Anticancer Activity Promoted by Ligand Diversity in Diiron Thiocarbyne Complexes

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 287, P. 117364 - 117364

Published: Feb. 5, 2025

Language: Английский

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Photo-Activated Ferrocene-Iridium(III) Prodrug Induces Immunogenic Cell Death in Melanoma Stem Cells

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Cancer stem cells (CSCs) are key contributors to tumor resistance, recurrence, and metastasis. Conventional chemotherapy often fails target eradicate CSCs, significantly impairing their therapeutic efficacy. Herein, we design synthesize a photoactivated ferrocene-iridium(III) complex (Ir-3) achieve immunotherapy against melanoma (including cells). In short, Ir-3 effectively targets mitochondria dissociates under light irradiation produce cytotoxic Ir(III) photosensitizer Fe2+ ions. They can generate reactive oxygen species by the Fenton reaction, robustly induce ferroptosis autophagy, eventually trigger immunogenic cell death in Furthermore, exposure, inhibits cell-related properties promotes macrophage-mediated phagocytosis of cells. For vivo studies, is encapsulated DSPE-PEG 2000 form tumor-targeting Ir-3@PEG nanoparticles. After photoactivation, inhibit primary distant tumors, stemness cells, innate adaptive immune responses.

Language: Английский

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In Situ Investigation of Intercellular Communication in Ferroptosis Integrated Scanning Electrochemical Microscopy with Microfluidic Devices

ACS Sensors, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Ferroptosis has been recognized as a potential treatment for various cancers. Still, in the complex tumor microenvironment, communication between cancer cells and tumor-associated macrophages (TAMs) plays crucial role tumorigenesis progression. In this work, scanning electrochemical microscopy (SECM) combined with microfluidic devices to enable on-chip cell coculture situ investigation of triple-negative breast (TNBCs) TAMs ferroptosis. system, TNBCs were used responding signaling cells, respectively. By monitoring changes key parameters (ROS, glutathione (GSH), membrane permeability) Erastin-induced ferroptosis, it was found that partially restored reduced GSH efflux, increased ROS release, impaired barrier TNBCs, indicating can suppress TNBC Mechanistically, could promote M2 macrophage polarization, M2-TAMs achieved suppression ferroptosis through STAT3-related pathway. After inhibition STAT3, release permeability well decreased efflux monitored by SECM, demonstrating intercellular mechanism Therefore, work provides strategy targeting ferroptosis-based therapy.

Language: Английский

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Graphene Nanocomposites in the Targeting Tumor Microenvironment: Recent Advances in TME Reprogramming

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4525 - 4525

Published: May 9, 2025

Graphene-based materials (GBMs) have shown significant promise in cancer therapy due to their unique physicochemical properties, biocompatibility, and ease of functionalization. Their ability target solid tumors, penetrate the tumor microenvironment (TME), act as efficient drug delivery platforms highlights potential nanomedicine. However, complex dynamic nature TME, characterized by metabolic heterogeneity, immune suppression, resistance, poses challenges effective treatment. GBMs offer innovative solutions enhancing targeting, facilitating deep tissue penetration, modulating pathways that contribute progression evasion. functionalization with targeting ligands biocompatible polymers improves biosafety specificity, while modulate cell interactions within TME presents new opportunities for immunotherapy. Given role reprogramming survival could be further exploited metabolism-targeted therapies disrupting glycolysis, mitochondrial respiration, lipid metabolism counteract immunosuppressive effects TME. This review focuses on discussing research studies design GBM nanocomposites enhanced biodegradability, minimized toxicity, improved efficacy delivering therapeutic agents intention reprogram anticancer therapy. Additionally, exploring combination immunotherapies treatments lead more personalized therapies. By addressing these challenges, play a pivotal overcoming current limitations treatment advancing precision oncology.

Language: Английский

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