Recent progress in ferroptosis: inducers and inhibitors

Cell Death Discovery, Journal Year: 2022, Volume and Issue: 8(1)

Published: Dec. 29, 2022

Ferroptosis is a new iron-dependent form of programmed cell death characterized by iron accumulation and lipid peroxidation. In recent years, ferroptosis has garnered enormous interest in disease treatment research communities pursuit to reveal the mechanism key targets because closely related pathophysiological processes many diseases. Recent studies have shown some targets, such as glutathione peroxidase 4 (GPX4) System Xc-, several inducers inhibitors been developed regulate these targets. With emergence on made developments. The selection use are very important for work. This paper briefly introduces regulatory metabolic pathway, lists categorizes commonly used recently inhibitors, discusses their medical application. ends with potential future direction ferroptosis.

Language: Английский

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A Hollow Amorphous Bimetal Organic Framework for Synergistic Cuproptosis/Ferroptosis/Apoptosis Anticancer Therapy via Disrupting Intracellular Redox Homeostasis and Copper/Iron Metabolisms

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(40)

Published: July 30, 2022

Abstract Cuproptosis is a very newly recognized regulated cell death modality that distinct from known mechanisms and shows enormous prospect in cancer treatment. However, its efficacy copper‐dependent restricted by strictly copper metabolism. Herein, novel copper/iron hybrid hollow amorphous metal organic framework (HaMOF) developed as an oxidative stress amplifier metabolic disrupter for synergistic cuproptosis/ferroptosis/apoptosis anticancer therapy. The HaMOF fabricated Cu 2+ , 3,3′‐dithiobis(propionohydrazide) Fe 3+ via unsaturated coordination‐etching integration strategy, then doxorubicin loaded followed surface decoration with hyaluronan. obtained DOX@Fe/CuTH exhibits tumor microenvironment‐triggered catalytic therapeutic property, wherein it can amplify cellular simultaneously boosting H 2 O production depleting glutathione. Moreover, cause mitochondrial dysfunction downregulate the expressions of transporter ATP7A iron FPN 1, thereby leading to disorders high retentions cytoplasm •OH generation. overloaded lipoylated protein dihydrolipoamide S‐acetyltransferase aggregation lead cuproptosis. Collectively, both augmented induce potent ferroptosis, which synergizes cuproptosis DOX‐mediated apoptosis efficiently suppress growth. This bimetallic nanoplatform provides new paradigm boost cuproptosis‐related therapies.

Language: Английский

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Stimuli-responsive ferroptosis for cancer therapy

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(12), P. 3955 - 3972

Published: Jan. 1, 2023

This review highlights recent advances in the utilization of various endogenous and exogenous stimuli to activate nanocarrier-based ferroptosis cancer therapy that can be effective treating conventional drug-resistant tumors.

Language: Английский

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Covalent Organic Framework Nanobowls as Activatable Nanosensitizers for Tumor‐Specific and Ferroptosis‐Augmented Sonodynamic Therapy

Advanced Science, Journal Year: 2023, Volume and Issue: 10(6)

Published: Jan. 3, 2023

Abstract Covalent organic frameworks (COFs) have attracted increasing attention for biomedical applications. COFs‐based nanosensitizers with uniform nanoscale morphology and tumor‐specific curative effects are in high demand; however, their synthesis is yet challenging. In this study, distinct COF nanobowls synthesized a controlled manner engineered as activatable sonodynamic activity. High crystallinity ensures an ordered porous structure of the efficient loading small‐molecule sonosensitizer rose bengal (RB). To circumvent non‐specific damage to normal tissues, sonosensitization effect specifically inhibited by situ growth manganese oxide (MnO x ) on RB‐loaded COFs. Upon reaction tumor‐overexpressed glutathione (GSH), “gatekeeper” MnO rapidly decomposed recover reactive oxygen species (ROS) generation capability under ultrasound irradiation. Increased intracellular ROS stress GSH consumption concomitantly induce ferroptosis improve efficacy. Additionally, unconventional bowl‐shaped renders enhanced tumor accumulation retention. The combination therapy achieves efficacy killing cancer cells inhibiting growth. This study paves way development morphologies biomedicine, offering paradigm realize ferroptosis‐augmented therapy.

Language: Английский

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Tumor Microenvironment Responsive Hollow Nanoplatform for Triple Amplification of Oxidative Stress to Enhance Cuproptosis‐Based Synergistic Cancer Therapy

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(13)

Published: Jan. 30, 2023

Cuproptosis is a recently discovered form of programmed cell death and shows great potential in cancer treatment. Herein, copper-dithiocarbamate chelate-doped artemisinin-loaded hollow nanoplatform (HNP) developed via chelation competition-induced hollowing strategy for cuproptosis-based combination therapy. The HNP exhibits tumor microenvironment-triggered catalytic activity, wherein liberated Cu2+ catalyzes artemisinin endogenous H2 O2 to produce C-centered radicals hydroxyl radicals, respectively. Meanwhile, the disulfide bonds-rich can deplete intracellular glutathione, thus triply amplifying oxidative stress. augmented stress sensitizes cells cuproptosis, causing prominent dihydrolipoamide S-acetyltransferase oligomerization mitochondrial dysfunction. Moreover, activate ferroptosis inhibiting GPX4 activity trigger apoptosis dithiocarbamate-copper chelate-mediated ubiquitinated proteins accumulation, resulting potent antitumor efficacy. Such cuproptosis/ferroptosis/apoptosis synergetic opens new avenue

Language: Английский

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Ultrasound-Based Micro-/Nanosystems for Biomedical Applications

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(13), P. 8307 - 8472

Published: June 26, 2024

Due to the intrinsic non-invasive nature, cost-effectiveness, high safety, and real-time capabilities, besides diagnostic imaging, ultrasound as a typical mechanical wave has been extensively developed physical tool for versatile biomedical applications. Especially, prosperity of nanotechnology nanomedicine invigorates landscape ultrasound-based medicine. The unprecedented surge in research enthusiasm dedicated efforts have led mass multifunctional micro-/nanosystems being applied biomedicine, facilitating precise diagnosis, effective treatment, personalized theranostics. deployment applications is rooted profound understanding relationship among composition, structure, property, bioactivity, application, performance. In this comprehensive review, we elaborate on general principles regarding design, synthesis, functionalization, optimization abundant particular, recent advancements imaging are meticulously summarized. Furthermore, systematically elucidate state-of-the-art studies concerning progress therapeutic targeting various pathological abnormalities including cancer, bacterial infection, brain diseases, cardiovascular metabolic diseases. Finally, conclude provide an outlook field with in-depth discussion challenges faced future developments further extensive clinical translation application.

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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MRI‐Guided Tumor Therapy Based on Synergy of Ferroptosis, Immunosuppression Reversal and Disulfidptosis

Small, Journal Year: 2024, Volume and Issue: 20(29)

Published: March 3, 2024

Triple negative breast cancer (TNBC) cells have a high demand for oxygen and glucose to fuel their growth spread, shaping the tumor microenvironment (TME) that can lead weakened immune system by hypoxia increased risk of metastasis. To disrupt this vicious circle improve therapeutic efficacy, strategy is proposed with synergy ferroptosis, immunosuppression reversal disulfidptosis. An intelligent nanomedicine GOx-IA@HMON@IO successfully developed realize strategy. The Fe release behaviors indicate glutathione (GSH)-responsive degradation HMON. results titanium sulfate assay, electron spin resonance (ESR) spectra, 5,5'-Dithiobis-(2-nitrobenzoic acid (DTNB) assay T

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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Tumor microenvironment targeted nano-drug delivery systems for multidrug resistant tumor therapy

Theranostics, Journal Year: 2025, Volume and Issue: 15(5), P. 1689 - 1714

Published: Jan. 2, 2025

In recent years, nano-drug delivery systems (Nano-DDS) that target the tumor microenvironment (TME) to overcome multidrug resistance (MDR) have become a research hotspot in field of cancer therapy. By precisely targeting TME and regulating its unique pathological features, such as hypoxia, weakly acidic pH, abnormally expressed proteins, etc., these Nano-DDS enable effective therapeutic agents reversal MDR. This scientific community is increasing investment development diversified exploring their anti-drug potential. Therefore, it particularly important conduct comprehensive review progress TME-targeted years. After brief introduction MDR, design principle structure liposomes, polymer micelles inorganic nanocarriers are focused on, characteristics described. It also demonstrates how break through MDR treatment various mechanisms, discusses synthetic innovation, results overcoming mechanisms. The was concluded with deliberations on key challenges future outlooks

Language: Английский

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