Targeting ferroptosis opens new avenues for the development of novel therapeutics

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Сен. 21, 2023

Abstract Ferroptosis is an iron-dependent form of regulated cell death with distinct characteristics, including altered iron homeostasis, reduced defense against oxidative stress, and abnormal lipid peroxidation. Recent studies have provided compelling evidence supporting the notion that ferroptosis plays a key pathogenic role in many diseases such as various cancer types, neurodegenerative disease, involving tissue and/or organ injury, inflammatory infectious diseases. Although precise regulatory networks underlie are largely unknown, particularly respect to initiation progression diseases, recognized bona fide target for further development treatment prevention strategies. Over past decade, considerable progress has been made developing pharmacological agonists antagonists these ferroptosis-related conditions. Here, we provide detailed overview our current knowledge regarding ferroptosis, its pathological roles, regulation during disease progression. Focusing on use chemical tools preclinical studies, also summarize recent advances targeting across growing spectrum ferroptosis-associated Finally, discuss new challenges opportunities potential strategy treating

Язык: Английский

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System Xc−/GSH/GPX4 axis: An important antioxidant system for the ferroptosis in drug-resistant solid tumor therapy

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Авг. 29, 2022

The activation of ferroptosis is a new effective way to treat drug-resistant solid tumors. Ferroptosis an iron-mediated form cell death caused by the accumulation lipid peroxides. intracellular imbalance between oxidant and antioxidant due abnormal expression multiple redox active enzymes will promote produce reactive oxygen species (ROS). So far, few pathways regulators have been discovered regulate ferroptosis. In particular, cystine/glutamate antiporter (System X c − ), glutathione peroxidase 4 (GPX4) (GSH) /GSH/GPX4 axis) plays key role in preventing peroxidation-mediated ferroptosis, because which could be inhibited blocking System axis. This review aims present current understanding mechanism based on axis treatment

Язык: Английский

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FSP1: a key regulator of ferroptosis

Trends in Molecular Medicine, Год журнала: 2023, Номер 29(9), С. 753 - 764

Опубликована: Июнь 24, 2023

Ferroptosis suppressor protein 1 (FSP1) is one of the main regulatory molecules ferroptosis. FSP1 functions through FSP1-coenzyme Q10 (CoQ10)-NAD(P)H axis and vitamin K redox cycle. regulated by upstream factors, including transcription factors noncoding RNA (ncRNA), subject to epigenetic modifications, which affect progress FSP1-related diseases. closely associated with poor prognosis malignant tumors plays an important role in disease treatment. This review aims provide a comprehensive understanding ferroptosis regulation summarizing pathways, possible mechanisms involving FSP1, relationship between

Язык: Английский

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Nanodrugs alleviate acute kidney injury: Manipulate RONS at kidney

Bioactive Materials, Год журнала: 2022, Номер 22, С. 141 - 167

Опубликована: Сен. 29, 2022

Currently, there are no clinical drugs available to treat acute kidney injury (AKI). Given the high prevalence and mortality rate of AKI, development effectively AKI is a huge unmet medical need research hotspot. Although existing evidence fully demonstrates that reactive oxygen nitrogen species (RONS) burst at site major contributor progression, heterogeneity, complexity, unique physiological structure make most antioxidant anti-inflammatory small molecule ineffective because lack targeting side effects. Recently, nanodrugs with intrinsic through control size, shape, surface properties have opened exciting prospects for treatment AKI. Many emerged address limitations current treatments. In this review, we systematically summarized first time about emerging exploit pathological features overcome traditional small-molecule achieve efficacy. First, analyzed structural characteristics main mechanism AKI: hypoxia, harmful substance accumulation-induced RONS renal despite multifactorial initiation heterogeneity Subsequently, introduced strategies used improve reviewed advances nano-RONS-sacrificial agents, nanozymes, nanocarriers antioxidants drugs. These demonstrated excellent therapeutic effects, such as greatly reducing oxidative stress damage, restoring function, low Finally, discussed challenges future directions translating into treatment.

Язык: Английский

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Oxygen Self-Generating Nanoreactor Mediated Ferroptosis Activation and Immunotherapy in Triple-Negative Breast Cancer

ACS Nano, Год журнала: 2023, Номер 17(5), С. 4667 - 4687

Опубликована: Март 2, 2023

The hypoxia microenvironment of solid tumors poses a technological bottleneck for ferroptosis and immunotherapy in clinical oncology. Nanoreactors based on special physiological signals tumor cells are able to avoid various tolerance mechanisms by alleviating the intracellular environment. Herein we reported nanoreactor Cu2-xSe that enabled conversion Cu elements between Cu+ Cu2+ generation O2 consumption GSH content. Furthermore, enhance catalytic ferroptosis-inducing activities nanoreactors, agonist Erastin was loaded ZIF-8 coating surface up-regulate expression NOX4 protein, increase H2O2 content, catalyze produce activate ferroptosis. In addition, nanoreactors were simultaneously functionalized with PEG polymer folic acid molecules, which ensured vivo blood circulation tumor-specific uptake. vitro experiments demonstrated self-supplying can amplify ability generate consume via interconversion Cu2+, impair GPX4/GSH pathway HIF-1α protein expression. At same time, environment, miR301, gene secreted exosomes decreased, ultimately affected phenotype polarization TAMs increased content IFN γ CD8+ T cells, further promoted induced Erastin-loaded nanoreactors. This combined therapeutic strategy activating immune response provides potential application.

Язык: Английский

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Deep Insight of Design, Mechanism, and Cancer Theranostic Strategy of Nanozymes

Nano-Micro Letters, Год журнала: 2023, Номер 16(1)

Опубликована: Ноя. 21, 2023

Since the discovery of enzyme-like activity Fe

Язык: Английский

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Bifunctional Cascading Nanozymes Based on Carbon Dots Promotes Photodynamic Therapy by Regulating Hypoxia and Glycolysis

ACS Nano, Год журнала: 2023, Номер 17(17), С. 16715 - 16730

Опубликована: Авг. 18, 2023

Photodynamic therapy (PDT) still faces great challenges with suitable photosensitizers, oxygen supply, and reactive species (ROS) accumulation, especially in the tumor microenvironment, feathering hypoxia, high glucose metabolism. Herein, a carbon dots (CDs)-based bifunctional nanosystem (MnZ@Au), acting as photosensitizer nanozyme cascading oxidase (GOx)- catalase (CAT)-like reactivity, was developed for improving hypoxia regulating metabolism to enhance PDT. The MnZ@Au constructed using Mn-doped CDs (Mn-CDs) core zeolitic imidazolate framework-8 (ZIF-8) shell form hybrid (MnZ), followed by anchoring ultrasmall Au nanoparticles (AuNPs) onto surface of MnZ through ion exchange situ reduction methods. catalyzed consumption generation GOx- CAT-like reactions, which further enhanced its own photothermal properties. In vitro vivo studies also confirmed that greatly improved penetration, promoted ROS PDT efficacy, leading efficient growth inhibition breast model. Besides, enabled photoacoustic (PA) imaging provide mapping Mn-CDs distribution saturation, showing real-time catalytic process vivo. 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG PET) validated decreased uptake tumors treated MnZ@Au. Therefore, integrated design provided promising strategy utilize regulate promote PDT, finally prevent deterioration.

Язык: Английский

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Targeting GPX4 in human cancer: Implications of ferroptosis induction for tackling cancer resilience

Cancer Letters, Год журнала: 2023, Номер 559, С. 216119 - 216119

Опубликована: Март 7, 2023

Язык: Английский

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Ferroptosis: principles and significance in health and disease

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Июнь 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.

Язык: Английский

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Near-Infrared-II-Activatable Self-Assembled Manganese Porphyrin-Gold Heterostructures for Photoacoustic Imaging-Guided Sonodynamic-Augmented Photothermal/Photodynamic Therapy

ACS Nano, Год журнала: 2023, Номер 18(1), С. 713 - 727

Опубликована: Дек. 20, 2023

Porphyrins and their derivatives are widely used as photosensitizers sonosensitizers in tumor treatment. Nevertheless, poor water solubility low chemical stability reduce singlet oxygen (1O2) yield and, consequently, photodynamic therapy (PDT) sonodynamic (SDT) efficiency. Although strategies for porphyrin molecule assembly have been developed to augment 1O2 generation, there is scope further improving PDT SDT efficiencies. Herein, we synthesized ordered manganese (SM) nanoparticles with well-defined self-assembled metalloporphyrin networks that enabled efficient energy transfer enhanced photocatalytic sonocatalytic activity production. Subsequently, Au were grown situ on the SM surface by anchoring terminal alkynyl of form plasmonic SMA heterostructures, which showed excellent near-infrared-II (NIR-II) region absorption photothermal properties, facilitated electron–hole pair separation transfer. With modification hyaluronic acid (HA), SMAH heterostructure nanocomposites exhibited good actively targeted cancer cells. Under NIR-II light ultrasound (US) irradiation, generates hyperthermia, a large amount 1O2, inducing cell damage. Both vitro vivo studies confirmed effectively suppressed growth decreasing GSH levels SDT-augmented PDT/PTT. Moreover, utilizing strong window, can achieve photoacoustic imaging-guided combined This work provides paradigm enhancing metalloporphyrins improve synergistic therapeutic effect SDT/PDT/PTT.

Язык: Английский

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