Stimuli-responsive ferroptosis for cancer therapy

Chemical Society Reviews, Год журнала: 2023, Номер 52(12), С. 3955 - 3972

Опубликована: Янв. 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.

Язык: Английский

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Mitophagy alleviates cisplatin-induced renal tubular epithelial cell ferroptosis through ROS/HO-1/GPX4 axis

International Journal of Biological Sciences, Год журнала: 2023, Номер 19(4), С. 1192 - 1210

Опубликована: Янв. 1, 2023

Cisplatin is widely recommended in combination for the treatment of tumors, thus inevitably increasing incidence cisplatin-induced acute kidney injury. Mitophagy a type mitochondrial quality control mechanism that degrades damaged mitochondria and maintains cellular homeostasis. Ferroptosis, new modality programmed cell death, characterized by iron-dependent phospholipid peroxidation oxidative membrane damage. However, role mitophagy ferroptosis disease unclear. Here, we investigated underlying both BNIP3-mediated PINK1-PARK2-mediated mitophagy-induced attenuation The results showed cisplatin induced injury, ROS release, intracellular iron accumulation, lipid kidney, which were aggravated Bnip3 knockout, Pink1 knockout or Park2 cisplatin-treated mice. Ferrstatin-1, synthetic antioxidative inhibitor, rescued caused inhibition mitophagy. Thus, present study elucidated novel protects against renal tubular epithelial through ROS/HO1/GPX4 axis.

Язык: Английский

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Ferroptosis as a potential target for cancer therapy

Cell Death and Disease, Год журнала: 2023, Номер 14(7)

Опубликована: Июль 24, 2023

Abstract Ferroptosis is a recently discovered essential type of cell death that mainly characterized by iron overload and lipid peroxidation. Emerging evidence suggests ferroptosis double-edged sword in human cancer. However, the precise underlying molecular mechanisms their differential roles tumorigenesis are unclear. Therefore, this review, we summarize briefly present key pathways ferroptosis, paying special attention to regulation as well its dual role an oncogenic tumor suppressor event various cancers. Moreover, multiple pharmacological activators summarized, prospect targeting cancer therapy further elucidated.

Язык: Английский

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The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Год журнала: 2023, Номер 4(1)

Опубликована: Окт. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Язык: Английский

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Transformable Supramolecular Self‐Assembled Peptides for Cascade Self‐Enhanced Ferroptosis Primed Cancer Immunotherapy

Advanced Materials, Год журнала: 2024, Номер 36(21)

Опубликована: Фев. 10, 2024

Abstract Immunotherapy has received widespread attention for its effective and long‐term tumor‐eliminating ability. However, immunogenic “cold” tumors, such as prostate cancer (PCa), the low immunogenicity of tumor itself is a serious obstacle to efficacy. Here, this work reports strategy enhance PCa by triggering cascade self‐enhanced ferroptosis in cells, turning from “hot”. This develops transformable self‐assembled peptide TEP‐FFG‐CRApY with alkaline phosphatase (ALP) responsiveness glutathione peroxidase 4 (GPX4) protein targeting. self‐assembles into nanoparticles under aqueous conditions transforms nanofibers response ALP during endosome/lysosome uptake promoting lysosomal membrane permeabilization (LMP). On one hand, released TEP‐FFG‐CRAY target GPX4 selectively degrade light irradiation, inducing ferroptosis; on other large amount leaked Fe 2+ further amplify through Fenton reaction. TEP‐FFG‐CRApY‐induced improves cell maturation dendritic cells (DCs) increasing intratumor T‐cell infiltration. More importantly, recovered T secreting amounts interferon‐gamma (IFN‐γ). provides novel molecular design synergistic molecularly targeted therapy tumors.

Язык: Английский

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Cellular metabolism: A key player in cancer ferroptosis

Cancer Communications, Год журнала: 2024, Номер 44(2), С. 185 - 204

Опубликована: Янв. 13, 2024

Abstract Cellular metabolism is the fundamental process by which cells maintain growth and self‐renewal. It produces energy, furnishes raw materials, intermediates for biomolecule synthesis, modulates enzyme activity to sustain normal cellular functions. foundation of life processes plays a regulatory role in various biological functions, including programmed cell death. Ferroptosis recently discovered form iron‐dependent The inhibition ferroptosis crucial tumorigenesis tumor progression. However, metabolism, particularly glucose amino acid cancer not well understood. Here, we reviewed glucose, lipid, acid, iron selenium involvement elucidate impact different metabolic pathways on this process. Additionally, provided detailed overview agents used induce ferroptosis. We explained that maintaining intracellular redox homeostasis disrupting these renders them more susceptible iron‐induced death, resulting enhanced killing. combination inducers inhibitors may be novel approach future therapy an important strategy advance development treatments.

Язык: Английский

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The Chemical Reactivity of Membrane Lipids

Chemical Reviews, Год журнала: 2024, Номер 124(6), С. 3284 - 3330

Опубликована: Март 18, 2024

It is well-known that aqueous dispersions of phospholipids spontaneously assemble into bilayer structures.These structures have numerous applications across chemistry and materials science form the fundamental structural unit biological membrane.The particular environment lipid bilayer, with a water-poor low dielectric core surrounded by more polar better hydrated interfacial region, gives membrane biophysical physicochemical properties presents unique for chemical reactions to occur.Many different types molecule spanning range sizes, from dissolved gases through small organics proteins, are able interact membranes promote changes lipids subsequently affect bilayer.This Review describes reactivity exhibited in their form, an emphasis on conditions where well bilayers.Key topics include following: lytic glyceryl esters, including hydrolysis, aminolysis, transesterification; oxidation alkenes unsaturated fatty acids sterols, autoxidation singlet oxygen; headgroups, particularly reactive carbonyl species; E/Z isomerization alkenes.The consequences activity also discussed.

Язык: Английский

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Ferroptosis: The Entanglement between Traditional Drugs and Nanodrugs in Tumor Therapy

Advanced Healthcare Materials, Год журнала: 2023, Номер 12(12)

Опубликована: Янв. 19, 2023

Ferroptosis is a non-apoptotic programmed cell death caused by the accumulation of lipid peroxide. System Xc-/glutathione peroxidase 4 (GPX4) axis and iron are two main pathways regulating ferroptosis. Simultaneously, multiple also involved in ferroptosis regulation. an intense area current study. With improvement regulatory mechanisms that underlie ferroptosis, variety drugs associated with have been discovered developed for cancer therapy. Among them, traditional were initially. Small molecule compounds regulate signaling pathway complexes promote Fenton reaction become important inducing In recent years, emerging development nanotechnology has promoted research nanodrugs. Iron-based nanomaterials extensively tested as ferroptosis-inducing agents. Furthermore, nanoscale drug delivery systems offer suitable scaffold therapies. Traditional nanodrugs complementary, each their own strengths limitations. This review describes latest studies on regulation tumor cells focuses entanglement between To conclude, challenges perspectives this field put forward.

Язык: Английский

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The initiator of neuroexcitotoxicity and ferroptosis in ischemic stroke: Glutamate accumulation

Frontiers in Molecular Neuroscience, Год журнала: 2023, Номер 16

Опубликована: Март 23, 2023

Glutamate plays an important role in excitotoxicity and ferroptosis. Excitotoxicity occurs through over-stimulation of glutamate receptors, specifically NMDAR, while the non-receptor-mediated pathway, high concentrations reduce cystine uptake by inhibiting System Xc-, leading to intracellular glutathione depletion resulting ROS accumulation, which contributes increased lipid peroxidation, mitochondrial damage, ultimately Oxidative stress appears crosstalk between ferroptosis, it is essential maintain homeostasis inhibit oxidative responses vivo . As researchers work develop natural compounds further investigate complex mechanisms regulatory functions ferroptosis excitotoxicity, new avenues will be available for effective treatment ischaemic stroke. Therefore, this paper provides a review molecular glutamate-mediated

Язык: Английский

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Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(16), С. 12928 - 12928

Опубликована: Авг. 18, 2023

Iron is essential for all organisms and cells. Diseases of iron imbalance affect billions patients, including those with overload other forms toxicity. Excess load an adverse prognostic factor diseases can cause serious organ damage fatalities following chronic red blood cell transfusions in patients many conditions, hemoglobinopathies, myelodyspasia, hematopoietic stem transplantation. Similar toxicity excess body but at a slower rate disease progression found idiopathic haemochromatosis patients. deposition different regions the brain suspected has been identified by MRI T2* similar methods neurodegenerative diseases, Alzheimer’s Parkinson’s disease. Based on its role as major biological catalyst free radical reactions Fenton reaction, also implicated associated pathology tissue damage. Furthermore, recent discovery ferroptosis, which death program based generation membrane lipid oxidation, sparked thousands investigations association cardiac, kidney, liver, cancer infections. The implications labile, non-protein bound form complexes dietary molecules such vitamin C drugs doxorubicin xenobiotic relation to carcinogenesis are discussed. In each case toxicity, mechanistic insights, diagnostic criteria, molecular interactions design new effective therapeutic interventions future targeted strategies. particular, this approach successful treatment most loading conditions especially transition thalassemia from fatal due protocols resulting complete elimination

Язык: Английский

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