Engineering Ultrasmall Ferroptosis-Targeting and Reactive Oxygen/Nitrogen Species-Scavenging Nanozyme for Alleviating Acute Kidney Injury
About: This article is published in Advanced Functional Materials.The article was published on 2021-11-27 and is currently open access. It has received 15 citations till now.
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TL;DR: In this article , the authors summarized the emerging nanodrugs that exploit the pathological and physiological features of the kidney to overcome the limitations of traditional small-molecule drugs to achieve high AKI efficacy.
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TL;DR: In this article , a bimetallic nanozyme (Pt50Sn50) with the photothermal enhancement of dual enzymatic activities for tumor catalytic therapy was developed. But it remains a significant challenge to fabricate highly efficient nanozymes acting in the tumor microenvironment.
Abstract: Specific generation of reactive oxygen species (ROS) within tumors in situ catalyzed by nanozymes is a promising strategy for cancer therapeutics. However, it remains a significant challenge to fabricate highly efficient nanozymes acting in the tumor microenvironment. Herein, we develop a bimetallic nanozyme (Pt50Sn50) with the photothermal enhancement of dual enzymatic activities for tumor catalytic therapy. The structures and activities of PtSn bimetallic nanoclusters (BNCs) with different Sn content are explored and evaluated systematically. Experimental comparisons show that the Pt50Sn50 BNCs exhibit the highest activities among all those investigated, including enzymatic activity and photothermal property, due to the generation of SnO2-x with oxygen vacancy (Ovac) sites on the surface of Pt50Sn50 BNCs. Specifically, the Pt50Sn50 BNCs exhibit photothermal-enhanced peroxidase-like and catalase-like activities, as well as a significantly enhanced anticancer efficacy in both multicellular tumor spheroids and in vivo experiments. Due to the high X-ray attenuation coefficient and excellent light absorption property, the Pt50Sn50 BNCs also show dual-mode imaging capacity of computed tomography and photoacoustic imaging, which could achieve in vivo real-time monitoring of the therapeutic process. Therefore, this work will advance the development of noble-metal nanozymes with optimal composition for efficient tumor catalytic therapy.
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TL;DR: In this article , a promising cytoprotective agent (Fe-NC SAzymes) with multiple enzyme-mimicking activities was fabricated based on the reaction of Schiff bases with Fe ions via one-pot solvothermal method.
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TL;DR: In this paper , the gold nanoparticles-embedded ceria nanoparticles (Au/CeO2) with enhanced antioxidant activities are designed to block this cycle reaction for treating IBD by scavenging overproduced reactive oxygen species (ROS).
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References
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TL;DR: In this article, the period prevalence of acute renal failure (ARF) requiring renal replacement therapy (RRT) was found to be between 5% and 6% and was associated with a high hospital mortality rate.
Abstract: ContextAlthough acute renal failure (ARF) is believed to be common in the setting
of critical illness and is associated with a high risk of death, little is
known about its epidemiology and outcome or how these vary in different regions
of the world.ObjectivesTo determine the period prevalence of ARF in intensive care unit (ICU)
patients in multiple countries; to characterize differences in etiology, illness
severity, and clinical practice; and to determine the impact of these differences
on patient outcomes.Design, Setting, and PatientsProspective observational study of ICU patients who either were treated
with renal replacement therapy (RRT) or fulfilled at least 1 of the predefined
criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23
countries.Main Outcome MeasuresOccurrence of ARF, factors contributing to etiology, illness severity,
treatment, need for renal support after hospital discharge, and hospital mortality.ResultsOf 29 269 critically ill patients admitted during the study period,
1738 (5.7%; 95% confidence interval [CI], 5.5%-6.0%) had ARF during their
ICU stay, including 1260 who were treated with RRT. The most common contributing
factor to ARF was septic shock (47.5%; 95% CI, 45.2%-49.5%). Approximately
30% of patients had preadmission renal dysfunction. Overall hospital mortality
was 60.3% (95% CI, 58.0%-62.6%). Dialysis dependence at hospital discharge
was 13.8% (95% CI, 11.2%-16.3%) for survivors. Independent risk factors for
hospital mortality included use of vasopressors (odds ratio [OR], 1.95; 95%
CI, 1.50-2.55; P<.001), mechanical ventilation
(OR, 2.11; 95% CI, 1.58-2.82; P<.001), septic
shock (OR, 1.36; 95% CI, 1.03-1.79; P = .03),
cardiogenic shock (OR, 1.41; 95% CI, 1.05-1.90; P = .02),
and hepatorenal syndrome (OR, 1.87; 95% CI, 1.07-3.28; P = .03).ConclusionIn this multinational study, the period prevalence of ARF requiring
RRT in the ICU was between 5% and 6% and was associated with a high hospital
mortality rate.
3,706 citations
TL;DR: Targeted metabolomic profiling and chemoproteomics revealed that GPX4 is an essential regulator of ferroptotic cancer cell death and sensitivity profiling in 177 cancer cell lines revealed that diffuse large B cell lymphomas and renal cell carcinomas are particularly susceptible to GPx4-regulated ferroPTosis.
3,457 citations
TL;DR: Pharmacological targeting of ACSL4 with thiazolidinediones, a class of antidiabetic compound, ameliorated tissue demise in a mouse model of ferroptosis, suggesting that ACSL 4 inhibition is a viable therapeutic approach to preventing ferroPTosis-related diseases.
Abstract: Ferroptosis is a form of regulated necrotic cell death controlled by glutathione peroxidase 4 (GPX4). At present, mechanisms that could predict sensitivity and/or resistance and that may be exploited to modulate ferroptosis are needed. We applied two independent approaches-a genome-wide CRISPR-based genetic screen and microarray analysis of ferroptosis-resistant cell lines-to uncover acyl-CoA synthetase long-chain family member 4 (ACSL4) as an essential component for ferroptosis execution. Specifically, Gpx4-Acsl4 double-knockout cells showed marked resistance to ferroptosis. Mechanistically, ACSL4 enriched cellular membranes with long polyunsaturated ω6 fatty acids. Moreover, ACSL4 was preferentially expressed in a panel of basal-like breast cancer cell lines and predicted their sensitivity to ferroptosis. Pharmacological targeting of ACSL4 with thiazolidinediones, a class of antidiabetic compound, ameliorated tissue demise in a mouse model of ferroptosis, suggesting that ACSL4 inhibition is a viable therapeutic approach to preventing ferroptosis-related diseases.
1,626 citations
TL;DR: The discovery of ferroptosis, the mechanism of ferraptosis regulation, and its increasingly appreciated relevance to both normal and pathological physiology are summarized.
1,562 citations
TL;DR: In this paper, the authors provide a critical analysis of the current molecular mechanisms and regulatory networks of ferroptosis, the potential physiological functions of the potential therapeutic roles, and its pathological roles, together with a potential for therapeutic targeting.
Abstract: The research field of ferroptosis has seen exponential growth over the past few years, since the term was coined in 2012. This unique modality of cell death, driven by iron-dependent phospholipid peroxidation, is regulated by multiple cellular metabolic pathways, including redox homeostasis, iron handling, mitochondrial activity and metabolism of amino acids, lipids and sugars, in addition to various signalling pathways relevant to disease. Numerous organ injuries and degenerative pathologies are driven by ferroptosis. Intriguingly, therapy-resistant cancer cells, particularly those in the mesenchymal state and prone to metastasis, are exquisitely vulnerable to ferroptosis. As such, pharmacological modulation of ferroptosis, via both its induction and its inhibition, holds great potential for the treatment of drug-resistant cancers, ischaemic organ injuries and other degenerative diseases linked to extensive lipid peroxidation. In this Review, we provide a critical analysis of the current molecular mechanisms and regulatory networks of ferroptosis, the potential physiological functions of ferroptosis in tumour suppression and immune surveillance, and its pathological roles, together with a potential for therapeutic targeting. Importantly, as in all rapidly evolving research areas, challenges exist due to misconceptions and inappropriate experimental methods. This Review also aims to address these issues and to provide practical guidelines for enhancing reproducibility and reliability in studies of ferroptosis. Finally, we discuss important concepts and pressing questions that should be the focus of future ferroptosis research.
1,243 citations