Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 8, 2024

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation iron-dependent membrane-localized lipid peroxides. It acts as an innate tumor suppressor mechanism and participates in biological processes tumors. Intriguingly, mesenchymal dedifferentiated cancer cells, which are usually resistant to apoptosis traditional therapies, exquisitely vulnerable ferroptosis, further underscoring its potential treatment approach for cancers, especially refractory cancers. However, impact ferroptosis on extends beyond direct cytotoxic effect cells. induction not only inhibits but also promotes development due negative anticancer immunity. Thus, comprehensive understanding role crucial successful translation therapy from laboratory clinical applications. In this review, we provide overview recent advancements cancer, covering molecular mechanisms, functions, regulatory pathways, interactions with microenvironment. We summarize applications immunotherapy, radiotherapy, systemic therapy, well inhibition various conditions. finally discuss markers, current challenges future directions cancer.

Language: Английский

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The roles of ferroptosis in cancer: Tumor suppression, tumor microenvironment, and therapeutic interventions

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(4), P. 513 - 534

Published: April 1, 2024

Language: Английский

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Ferroptosis: principles and significance in health and disease

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 6, 2024

Abstract Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic pathway in 2012, ferroptosis has emerged crucial mechanism numerous physiological pathological contexts, leading to significant therapeutic advancements across wide range diseases. This review summarizes the fundamental mechanisms regulatory pathways underlying ferroptosis, including both GPX4-dependent -independent antioxidant mechanisms. Additionally, we examine involvement various conditions, cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, metabolic disorders. Specifically, explore role response chemotherapy, radiotherapy, immunotherapy, nanotherapy, targeted therapy. Furthermore, discuss pharmacological strategies for modulating potential biomarkers monitoring this process. Lastly, elucidate interplay between other forms regulated death. Such insights hold promise advancing our understanding context human health disease.

Language: Английский

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Light-Triggered Nanozymes Remodel the Tumor Hypoxic and Immunosuppressive Microenvironment for Ferroptosis-Enhanced Antitumor Immunity

ACS Nano, Journal Year: 2024, Volume and Issue: 18(19), P. 12261 - 12275

Published: April 29, 2024

Cancer immunotherapy holds significant promise for addressing diverse malignancies. Nevertheless, its efficacy remains constrained by the intricate tumor immunosuppressive microenvironment. Herein, a light-triggered nanozyme Fe-TCPP-R848-PEG (Fe-MOF-RP) was designed remodeling The Fe-TCPP-MOFs were utilized not only as core catalysis component against destruction but also biocompatible delivery vector of an immunologic agonist, improving long circulation and enrichment. Concurrently, it catalyzes decomposition H2O2 within tumor, yielding oxygen to augment photodynamic therapy. induced ferroptosis, in synergy with therapy, prompts liberation tumor-associated antigens from cells inducing immunogenic cell death. Phototriggered on-demand release R848 agonists stimulated maturation dendritic reverted tumor-promoting M2 phenotypes into adoptive M1 macrophages, which further reshaped Notably, effectively restrains well-established tumors, such B16F10 melanoma. Moreover, demonstrates distal tumor-inhibiting effect upon situ light treatment. What is more, lung metastasis model, elicits robust immune memory, conferring enduring protection rechallenge. Our study presents straightforward broadly applicable strategy crafting nanozymes potential thwart cancer recurrence metastasis.

Language: Английский

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Dual-targeting nanozyme combined with aPD-L1-based immunotherapy for combating cancer recurrence and metastasis

Materials Today, Journal Year: 2024, Volume and Issue: 73, P. 79 - 95

Published: Feb. 12, 2024

Language: Английский

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An Intelligent Cupreous Nanoplatform with Self-Supplied H₂O₂ and Cu²⁺/Cu⁺ Conversion to Boost Cuproptosis and Chemodynamic Combined Therapy

Chemistry of Materials, Journal Year: 2024, Volume and Issue: 36(2), P. 815 - 828

Published: Jan. 11, 2024

Cuproptosis is a newly identified copper-dependent cell death and holds great promise for cancer therapy. However, transporting enough copper into cells challenge. Herein, an intelligent cupreous nanoplatform (denoted as CuO2-MSN@TA-Cu2+), consisting of in situ formation CuO2 within mesoporous silica nanoparticles (MSN) then deposition with tannic acid (TA)-Cu2+ complex, designed developed to realize on-demand delivery cuproptosis-based combination CuO2-MSN@TA-Cu2+ exhibits tumor microenvironment-triggered therapeutic activity, wherein the outer TA-Cu2+ complex readily disassembled release Cu2+ liberate internal produce H2O2. The overloaded can not only directly convert endogenous H2O2 self-supplied highly toxic hydroxyl radicals chemodynamic therapy (CDT) via Cu-based Fenton-like reaction but also undergo glutathione-mediated reduction Cu+ species induce potent cellular cuproptosis enhance CDT. experimental results indicate that produces remarkable cytotoxicity against significantly suppresses growth by 93.42% mice-bearing 4T1 breast tumors. This work provides new paradigm boost cuproptosis-related may inspire design advanced nanoplatforms.

Language: Английский

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Progress and Challenges in Tumor Ferroptosis Treatment Strategies: A Comprehensive Review of Metal Complexes and Nanomedicine

Small, Journal Year: 2024, Volume and Issue: 20(25)

Published: Jan. 14, 2024

Abstract Ferroptosis is a new form of regulated cell death featuring iron‐dependent lipid peroxides accumulation to kill tumor cells. A growing body evidence has shown the potential ferroptosis‐based cancer therapy in eradicating refractory malignancies that are resistant apoptosis‐based conventional therapies. In recent years, studies have reported number ferroptosis inducers can increase vulnerability cells by regulating ferroptosis‐related signaling pathways. Encouraged rapid development ferroptosis‐driven therapies, interdisciplinary fields combine ferroptosis, pharmaceutical chemistry, and nanotechnology focused. First, prerequisites metabolic pathways for briefly introduced. Then, detail emerging designed boost ferroptosis‐induced therapy, including metal complexes, metal‐based nanoparticles, metal‐free nanoparticles summarized. Subsequently, application synergistic strategies with apoptosis other emphasis on use both cuproptosis induce redox dysregulation intracellular bimetallic copper/iron metabolism disorders during treatment discussed. Finally, challenges associated clinical translation future directions potentiating therapies highlighted.

Language: Английский

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Chemical Design of Magnetic Nanomaterials for Imaging and Ferroptosis-Based Cancer Therapy

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Ferroptosis, an iron-dependent form of regulatory cell death, has garnered significant interest as a therapeutic target in cancer treatment due to its distinct characteristics, including lipid peroxide generation and redox imbalance. However, clinical application oncology is currently limited by issues such suboptimal efficacy potential off-target effects. The advent nanotechnology provided new way for overcoming these challenges through the development activatable magnetic nanoparticles (MNPs). These innovative MNPs are designed improve specificity ferroptosis induction. This Review delves into chemical biological principles guiding design ferroptosis-based therapies imaging-guided therapies. It discusses mechanisms attributes ferroptosis, composition MNPs, their mechanism action inducers, integration with advanced imaging techniques monitoring. Additionally, we examine convergence other strategies, chemodynamic therapy, photothermal photodynamic sonodynamic immunotherapy, within context nanomedicine strategies utilizing MNPs. highlights multifunctional surpass limitations conventional treatments, envisioning future drug-resistance-free, precision diagnostics treating recalcitrant cancers.

Language: Английский

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Metal–organic framework-based smart stimuli-responsive drug delivery systems for cancer therapy: advances, challenges, and future perspectives

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 28, 2025

Cancer treatment is currently one of the most critical healthcare issues globally. A well-designed drug delivery system can precisely target tumor tissues, improve efficacy, and reduce damage to normal tissues. Stimuli-responsive systems (SRDDSs) have shown promising application prospects. Intelligent nano responsive endogenous stimuli such as weak acidity, complex redox characteristics, hypoxia, active energy metabolism, well exogenous like high temperature, light, pressure, magnetic fields are increasingly being applied in chemotherapy, radiotherapy, photothermal therapy, photodynamic various other anticancer approaches. Metal–organic frameworks (MOFs) become candidate materials for constructing SRDDSs due their large surface area, tunable porosity structure, ease synthesis modification, good biocompatibility. This paper reviews MOF-based modes cancer therapy. It summarizes key aspects, including classification, synthesis, modifications, loading modes, stimuli-responsive mechanisms, roles different modalities. Furthermore, we address current challenges summarize potential applications artificial intelligence MOF synthesis. Finally, propose strategies enhance efficacy safety SRDDSs, ultimately aiming at facilitating clinical translation.

Language: Английский

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A Multifunctional Covalent Organic Framework Nanozyme for Promoting Ferroptotic Radiotherapy against Esophageal Cancer

ACS Nano, Journal Year: 2023, Volume and Issue: 17(20), P. 20445 - 20461

Published: Oct. 6, 2023

Radiotherapy is inevitably accompanied by some degree of radiation resistance, which leads to local recurrence and even therapeutic failure. To overcome this limitation, herein, we report the room-temperature synthesis an iodine- ferrocene-loaded covalent organic framework (COF) nanozyme, termed TADI-COF-Fc, for enhancement radiotherapeutic efficacy in treatment radioresistant esophageal cancer. The iodine atoms on COF not only exerted a direct effect radiotherapy, increasing its X-ray absorption, but also promoted radiolysis water, increased production reactive oxygen species (ROS). In addition, ferrocene surface decoration disrupted redox homeostasis levels hydroxyl lipid peroxide radicals depleting intracellular antioxidants. Both vitro vivo experiments substantiated excellent response TADI-COF-Fc. This study demonstrates potential COF-based multinanozymes as radiosensitizers suggests possible integration strategy combination oncotherapy.

Language: Английский

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