The Metabolic Underpinnings of Ferroptosis

Cell Metabolism, Год журнала: 2020, Номер 32(6), С. 920 - 937

Опубликована: Ноя. 20, 2020

Язык: Английский

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Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Июнь 20, 2022

Abstract In recent years, immunotherapy represented by immune checkpoint inhibitors (ICIs) has led to unprecedented breakthroughs in cancer treatment. However, the fact that many tumors respond poorly or even not ICIs, partly caused absence of tumor-infiltrating lymphocytes (TILs), significantly limits application ICIs. Converting these “cold” into “hot” may ICIs is an unsolved question immunotherapy. Since it a general characteristic cancers resist apoptosis, induction non-apoptotic regulated cell death (RCD) emerging as new treatment strategy. Recently, several studies have revealed interaction between RCD and antitumor immunity. Specifically, autophagy, ferroptosis, pyroptosis, necroptosis exhibit synergistic responses while possibly exerting inhibitory effects on responses. Thus, targeted therapies (inducers inhibitors) against combination with exert potent activity, resistant This review summarizes multilevel relationship immunity RCD, including necroptosis, potential targeting improve efficacy malignancy.

Язык: Английский

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Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Окт. 9, 2023

Abstract The use of nanotechnology has the potential to revolutionize detection and treatment cancer. Developments in protein engineering materials science have led emergence new nanoscale targeting techniques, which offer renewed hope for cancer patients. While several nanocarriers medicinal purposes been approved human trials, only a few authorized clinical cells. In this review, we analyze some formulations discuss challenges translating findings from lab clinic. This study highlights various compounds that can be used selective tumor inherent difficulties therapy. Nanotechnology provides promising platform improving future, but further research is needed overcome current limitations translation. Graphical

Язык: Английский

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Ferroptosis in cancer and cancer immunotherapy

Cancer Communications, Год журнала: 2022, Номер 42(2), С. 88 - 116

Опубликована: Фев. 1, 2022

Abstract The hallmark of tumorigenesis is the successful circumvention cell death regulation for achieving unlimited replication and immortality. Ferroptosis a newly identified type dependent on lipid peroxidation which differs from classical programmed in terms morphology, physiology biochemistry. broad spectrum injury tumor tolerance are main reasons radiotherapy chemotherapy failure. effective rate immunotherapy as new treatment method less than 30%. can be seen radiotherapy, chemotherapy, immunotherapy; therefore, ferroptosis activation may potential strategy to overcome drug resistance mechanism traditional cancer treatments. In this review, characteristics causes by briefly described. addition, three metabolic regulations its crosstalk with signaling pathways summarized. Collectively, these findings suggest vital role based interaction immunotherapy, thus, indicating remarkable treatment.

Язык: Английский

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Ferroptosis heterogeneity in triple-negative breast cancer reveals an innovative immunotherapy combination strategy

Cell Metabolism, Год журнала: 2022, Номер 35(1), С. 84 - 100.e8

Опубликована: Окт. 17, 2022

Treatment of triple-negative breast cancer (TNBC) remains challenging. Deciphering the orchestration metabolic pathways in regulating ferroptosis will provide new insights into TNBC therapeutic strategies. Here, we integrated multiomics data our large cohort (n = 465) to develop atlas. We discovered that TNBCs had heterogeneous phenotypes ferroptosis-related metabolites and pathways. The luminal androgen receptor (LAR) subtype was characterized by upregulation oxidized phosphatidylethanolamines glutathione metabolism (especially GPX4), which allowed utilization GPX4 inhibitors induce ferroptosis. Furthermore, verified inhibition not only induced tumor but also enhanced antitumor immunity. combination anti-PD1 possessed greater efficacy than monotherapy. Clinically, higher expression correlated with lower cytolytic scores worse prognosis immunotherapy cohorts. Collectively, this study demonstrated landscape revealed an innovative strategy for refractory LAR tumors.

Язык: Английский

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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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Acidity‐Activatable Dynamic Nanoparticles Boosting Ferroptotic Cell Death for Immunotherapy of Cancer

Advanced Materials, Год журнала: 2021, Номер 33(31)

Опубликована: Июнь 25, 2021

Abstract Immunotherapy shows promising therapeutic potential for long‐term tumor regression. However, current cancer immunotherapy displays a low response rate due to insufficient immunogenicity of the cells. To address these challenges, herein, intracellular‐acidity‐activatable dynamic nanoparticles eliciting by inducing ferroptosis cells are engineered. The engineered integrating an ionizable block copolymer and acid‐liable phenylboronate ester (PBE) covalent bonds tumor‐specific delivery inducer, glutathione peroxidase 4 inhibitor RSL‐3. can stably encapsulate RSL‐3 inside hydrophobic core via π–π stacking interaction with PBE groups at neutral pH (pH = 7.4), while releasing payload in endocytic vesicles 5.8–6.2) acidity‐triggered cleavage bonds. Furthermore, perform acid‐activatable photodynamic therapy protonation core, significantly recruit tumor‐infiltrating T lymphocytes interferon gamma secretion, thus sensitize RSL‐3‐inducible ferroptosis. combination nanoparticle‐induced blockade programmed death ligand 1 efficiently inhibits growth B16‐F10 melanoma lung metastasis 4T1 breast tumors, suggesting induction promoting immunotherapy.

Язык: Английский

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Ferroptosis in the tumor microenvironment: perspectives for immunotherapy

Trends in Molecular Medicine, Год журнала: 2021, Номер 27(9), С. 856 - 867

Опубликована: Июль 23, 2021

Язык: Английский

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Recent applications of immunomodulatory biomaterials for disease immunotherapy

Exploration, Год журнала: 2022, Номер 2(6)

Опубликована: Май 23, 2022

Immunotherapy is used to regulate systemic hyperactivation or hypoactivation treat various diseases. Biomaterial-based immunotherapy systems can improve therapeutic effects through targeted drug delivery, immunoengineering, etc. However, the immunomodulatory of biomaterials themselves cannot be neglected. In this review, we outline with functions discovered in recent years and their applications disease treatment. These inflammation, tumors, autoimmune diseases by regulating immune cell function, exerting enzyme-like activity, neutralizing cytokines, The prospects challenges biomaterial-based modulation are also discussed.

Язык: Английский

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Renal Clearable Ultrasmall Single-Crystal Fe Nanoparticles for Highly Selective and Effective Ferroptosis Therapy and Immunotherapy

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(38), С. 15812 - 15823

Опубликована: Сен. 2, 2021

Iron-based nanoparticles have attracted much attention because of their ability to induce ferroptosis via a catalyzing Fenton reaction and further potentiate immunotherapy. However, current iron-based need be used in cooperation with other treatments or applied high dose for effective therapy low reactive oxygen species production efficacy. Here, we synthesized ultrasmall single-crystal Fe (bcc-USINPs) that stayed stable normal physiological environment but were highly active tumor microenvironment the selective acidic etching an Fe3O4 shell exposure Fe(0) core. The bcc-USINPs could efficiently cell immunogenetic death at very concentration. Intravenous injection iRGD-bcc-USINPs three doses 1 mg/kg effectively suppress growth, promote maturation dendritic cells, trigger adaptive T response. Combined programmed death-ligand (PD-L1) immune checkpoint blockade immunotherapy, iRGD-bcc-USINP-mediated greatly potentiated response developed strong memory. In addition, these USINPs quickly renal excreted no side effects tissues. These provide simple, safe, effective, selectively tumor-responsive delivery system ferroptosis-based

Язык: Английский

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