Tumor-Generated Reactive Oxygen Species Storm for High-Performance Ferroptosis Therapy

ACS Nano, Journal Year: 2023, Volume and Issue: 17(12), P. 11492 - 11506

Published: June 7, 2023

Ferroptosis therapy (FT) efficacy of tumors suffers from a relatively low concentration Fenton agents, limited hydrogen peroxide (H2O2) content, and insufficient acidity in the tumor environment (TME), which are unfavorable for reactive oxygen species (ROS) generation based on or Fenton-like reactions. The glutathione (GSH) overexpression TME can scavenge ROS abate FT performance. In this study, strategy storm specifically initiated by our developed nanoplatforms (TAF-HMON-CuP@PPDG) is proposed high-performance tumors. GSH initiates HMON degradation, resulting tamoxifen (TAF) copper (CuP) release TAF3-HMON-CuP3@PPDG. released TAF leads to enhanced acidification within cells, reacts with CuP producing Cu2+ H2O2. reaction between H2O2 generates Cu+, that Cu+ Cu2+, forming cyclic catalysis effect. generate GSSG. increased accelerate consumption decreases peroxidase 4 (GPX4) expression. All above reactions cells FT, demonstrated cancer tumor-bearing mice.

Language: Английский

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The Applications and Mechanisms of Superoxide Dismutase in Medicine, Food, and Cosmetics

Antioxidants, Journal Year: 2023, Volume and Issue: 12(9), P. 1675 - 1675

Published: Aug. 27, 2023

Superoxide dismutase (SOD) is a class of enzymes that restrict the biological oxidant cluster enzyme system in body, which can effectively respond to cellular oxidative stress, lipid metabolism, inflammation, and oxidation. Published studies have shown SOD (SODs) could maintain dynamic balance between production scavenging oxidants body prevent toxic effects free radicals, been be effective anti-tumor, anti-radiation, anti-aging studies. This research summarizes types, functions, regulatory mechanisms SODs, as well their applications medicine, food production, cosmetic production. SODs proven useful tool fighting disease, mimetics conjugates report developed successively improve effectiveness SODs. There are still obstacles solving membrane permeability persistence action, hot spot difficulty mining effect promoting application future.

Language: Английский

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Multi-enzyme Co-expressed Dual-Atom Nanozymes Induce Cascade Immunogenic Ferroptosis via Activating Interferon-γ and Targeting Arachidonic Acid Metabolism

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(16), P. 8965 - 8978

Published: April 14, 2023

Immunotherapy is currently the most promising treatment strategy for long-term tumor regression. However, current cancer immunotherapy shows low response rates due to insufficient immunogenicity of cells. Herein, we report a keep cells highly immunogenic by triggering cascade ferroptosis. We developed six-enzyme co-expressed nanoplatform: lipoxygenase (LOX) and phospholipase A2 (PLA2)-co-loaded FeCo/Fe-Co dual-metal atom nanozyme (FeCo/Fe-Co DAzyme/PL), which can not only induce initial ferroptosis through its own multi-enzyme mimetic activities but also up-regulate arachidonic acid (AA) expression synergize with CD8+ T cell-derived IFN-γ ACSL4-mediated During this process, DAzyme/PL lipid peroxidation (LPO) efficiently generating reactive oxygen species (ROS) depleting GSH GPX4 at sites. Additionally, free AA released from PLA2 catalysis converted into arachidonyl-CoA under activation ACSL4 stimulated IFN-γ, further incorporated phospholipids on membranes peroxidized participation LOX. Consequently, promote irreversible multiple ROS storms, GSH/GPX4 depletion, LOX catalysis, IFN-γ-mediated activation, constructing an effective pathway overcome drawbacks immunotherapy.

Language: Английский

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MnOOH-Catalyzed Autoxidation of Glutathione for Reactive Oxygen Species Production and Nanocatalytic Tumor Innate Immunotherapy

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(10), P. 5803 - 5815

Published: Feb. 27, 2023

The antioxidant system, signed with reduced glutathione (GSH) overexpression, is the key weapon for tumor to resist attack by reactive oxygen species (ROS). Counteracting ROS depletion GSH an effective strategy guarantee antitumor efficacy of nanocatalytic therapy. However, simply reducing concentration does not sufficiently improve response therapy intervention. Herein, a well-dispersed MnOOH nanocatalyst developed catalyze autoxidation and peroxidase-like reaction concurrently respectively promote H2O2 decomposition produce abundant such as hydroxyl radical (·OH), thereby generating highly superadditive catalytic therapeutic efficacy. Such that transforms endogenous "antioxidant" into "oxidant" may open new avenue development medicine. Moreover, released Mn2+ can activate sensitize cGAS-STING pathway damaged intratumoral DNA double-strands induced produced further macrophage maturation M1-polarization, which will boost innate immunotherapeutic Resultantly, simple medicine capable simultaneously catalyzing generation, mediating immune activation, holds great potential in treatment malignant tumors.

Language: Английский

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Ferroptosis Nanomedicine: Clinical Challenges and Opportunities for Modulating Tumor Metabolic and Immunological Landscape

ACS Nano, Journal Year: 2023, Volume and Issue: 17(16), P. 15328 - 15353

Published: Aug. 13, 2023

Ferroptosis, a type of regulated cell death driven by iron-dependent phospholipid peroxidation, has captured much attention in the field nanomedicine since it was coined 2012. Compared with other modes such as apoptosis and pyroptosis, ferroptosis many distinct features molecular mechanisms cellular morphology, representing promising strategy for treating cancers that are resistant to conventional therapeutic modalities. Moreover, recent insights collectively reveal is tightly connected maintenance tumor immune microenvironment (TIME), suggesting potential application therapies evoking robust antitumor immunity. From biochemical perspective, intricately multiple metabolic pathways, including iron metabolism, lipid redox etc., highlighting importance elucidate relationship between metabolism developing therapies. In this review, we provide comprehensive discussion on current understanding ferroptosis-inducing thoroughly discuss various traits tumors, which offer opportunities direct inhibition through nanointegrated approach. Extending from complex impact TIME, also discussed those important considerations development ferroptosis-based immunotherapy, challenges strategies enhance ferroptosis-enabled immunostimulatory effects while avoiding side effects. We envision study may facilitate translation nanomedicines treatment.

Language: Английский

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Nanozyme‐Based Regulation of Cellular Metabolism and Their Applications

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(10)

Published: April 5, 2023

Metabolism is the sum of enzyme-dependent chemical reactions, which produces energy in catabolic process and synthesizes biomass anabolic process, exhibiting high similarity mammalian cell, microbial plant cell. Consequently, loss or gain metabolic enzyme activity greatly affects cellular metabolism. Nanozymes, as emerging mimics with diverse functions adjustable catalytic activities, have shown attractive potential for regulation. Although basic tasks are highly similar cells from different species, concrete pathway varies intracellular structure species. Here, metabolism living organisms described similarities differences pathways among mammalian, microbial, regulation mechanism discussed. The recent progress on mainly including nutrient uptake utilization, production, accompanied redox reactions by kinds oxidoreductases their applications field disease therapy, antimicrobial sustainable agriculture systematically reviewed. Furthermore, prospects challenges nanozymes regulating cell also discussed, broaden application scenarios.

Language: Английский

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Smart Nanozymes for Cancer Therapy: The Next Frontier in Oncology

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(25)

Published: July 1, 2023

Nanomaterials that mimic the catalytic activity of natural enzymes in complex biological environment human body are called nanozymes. Recently, nanozyme systems have been reported with diagnostic, imaging, and/or therapeutic capabilities. Smart nanozymes strategically exploit tumor microenvironment (TME) by situ generation reactive species or modulation TME itself to result effective cancer therapy. This topical review focuses on such smart for diagnosis, and therapy modalities enhanced effects. The dominant factors guide rational design synthesis include an understanding dynamic TME, structure-activity relationships, surface chemistry imparting selectivity, site-specific therapy, stimulus-responsive activity. article presents a comprehensive analysis subject including diverse mechanisms different types systems, overview synergistic therapies. strategic application treatment can well be game changer future oncology. Moreover, recent developments may pave way deployment into other healthcare challenges, as genetic diseases, immune disorders, ageing.

Language: Английский

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Nanomaterials‐Induced Redox Imbalance: Challenged and Opportunities for Nanomaterials in Cancer Therapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(16)

Published: Feb. 21, 2024

Abstract Cancer cells typically display redox imbalance compared with normal due to increased metabolic rate, accumulated mitochondrial dysfunction, elevated cell signaling, and accelerated peroxisomal activities. This may regulate gene expression, alter protein stability, modulate existing cellular programs, resulting in inefficient treatment modalities. Therapeutic strategies targeting intra‐ or extracellular states of cancer at varying state progression trigger programmed death if exceeded a certain threshold, enabling therapeutic selectivity overcoming resistance radiotherapy chemotherapy. Nanotechnology provides new opportunities for modulating their excellent designability high reactivity. Various nanomaterials are widely researched enhance highly reactive substances (free radicals) production, disrupt the endogenous antioxidant defense systems, both. Here, physiological features described challenges illustrated. Then, that classified elaborated upon based on ability target regulations. Finally, future perspectives this field proposed. It is hoped review guidance design nanomaterials‐based approaches involving therapy, especially cancers resistant chemotherapy, etc.

Language: Английский

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A non‐metal single atom nanozyme for cutting off the energy and reducing power of tumors

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(16)

Published: Feb. 16, 2024

Enzymes are considered safe and effective therapeutic tools for various diseases. With the increasing integration of biomedicine nanotechnology, artificial nanozymes offer advanced controllability functionality in medical design. However, several notable gaps, such as catalytic diversity, specificity biosafety, still exist between their native counterparts. Here we report a non-metal single-selenium (Se)-atom nanozyme (SeSAE), which exhibits potent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mimetic activity. This novel single atom provides alternative to conventional metal-based catalysts effectively cuts off cellular energy reduction equivalents through its distinctive function tumors. In this study, have demonstrated substantial efficacy SeSAE an antitumor nanomedicine across diverse mouse models without discernible systemic adverse effects. The mechanism NADPH oxidase-like activity was rationalized by density functional theory calculations. Furthermore, comprehensive elucidation biological functions, cell death pathways, metabolic remodeling effects conducted, aiming provide valuable insights into development with clinical translation potential.

Language: Английский

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NADPH Oxidase‐Like Nanozyme for High‐Efficiency Tumor Therapy Through Increasing Glutathione Consumption and Blocking Glutathione Regeneration

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(11)

Published: Jan. 12, 2024

Abstract To counteract the high level of reactive oxygen species (ROS) caused by rapid growth, tumor cells resist oxidative stress accelerating production and regeneration intracellular glutathione (GSH). Numerous studies focus on consumption GSH, but GSH will enhance reduction to stress. Therefore, inhibiting GSH; while, consuming is great significance for breaking redox balance cells. Herein, a simple termed MnO x ‐coated Au (AMO) nanoflower, as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) nanoenzyme, reported efficient therapy. nanoparticles exhibit capability catalyze oxidation NADPH, hindering regeneration; concurrently functioning photothermal agent. During process eliminating releases Mn 2+ that subsequently engages in Fenton‐like reactions, ultimately facilitating implementation chemodynamic therapy (CDT). Overall, this NOX enzyme‐based nanoplatform enhances ROS generation disrupts state equilibrium, inducing apoptosis ferroptosis blocking increasing consumption, thereby achieving collaborative treatments involving (PTT), CDT, catalytic This research contributes NADPH targeted showcases potential nanozymes.

Language: Английский

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