Biodegradable Ferric Phosphate Nanocarriers with Tumor‐Specific Activation and Glutathione Depletion for Tumor Self‐Enhanced Ferroptosis and Chemotherapy

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(21)

Published: Jan. 31, 2024

Abstract Ferroptosis is a regulatory cell death that dependent on iron‐mediated lipid peroxidation and membrane damage. The use of iron‐based nanocarriers to activate ferroptosis great significance in oncotherapy. However, the limited endogenous hydrogen peroxide (H 2 O ) high expression glutathione (GSH) tumor cells restrict efficiency inducing ferroptosis. Herein, ferric phosphate nanotherapeutic system (denoted as FeP@HCPT‐HA) reported with H ‐supply GSH‐elimination properties for self‐enhanced chemotherapy. FeP@HCPT‐HA obtained by coprecipitation method situ loading 10‐hydroxycamptothecin (HCPT), followed modification hyaluronic acid (HA). actively targets CD44‐overexpressed degrades acidic microenvironment release HCPT, Fe 2+ 3+ . As chemotherapy drug, HCPT not only induces apoptosis but also supplies ‐mediated Fenton reaction enhance released depletes GSH redox between GSH, which down‐regulates peroxidase 4 (GPX4) enhances peroxidation, resulting enhanced integration targeting tumor‐specific activation, well GSH‐elimination, endow effective growth inhibition

Language: Английский

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Zinc–Iron Bimetallic Peroxides Modulate the Tumor Stromal Microenvironment and Enhance Cell Immunogenicity for Enhanced Breast Cancer Immunotherapy Therapy

ACS Nano, Journal Year: 2024, Volume and Issue: 18(15), P. 10542 - 10556

Published: April 1, 2024

Immunotherapy has emerged as a potential approach for breast cancer treatment. However, the rigid stromal microenvironment and low immunogenicity of tumors strongly reduce sensitivity to immunotherapy. To sensitize patients immunotherapy, hyaluronic acid-modified zinc peroxide–iron nanocomposites (Fe-ZnO2@HA, abbreviated FZOH) were synthesized remodel increase tumor immunogenicity. The constructed FZOH spontaneously generated highly oxidative hydroxyl radicals (·OH) that degrade acid (HA) in extracellular matrix (ECM), thereby reshaping enhancing blood perfusion, drug penetration, immune cell infiltration. Furthermore, not only triggers pyroptosis through activation caspase-1/GSDMD-dependent pathway but also induces ferroptosis various mechanisms, including increasing levels Fe2+ intracellular iron pool, downregulating expression FPN1 inhibit efflux, activating p53 signaling cause failure SLC7A11-GSH-GPX4 axis. Upon treatment with FZOH, 4T1 cells undergo both pyroptosis, exhibiting strong immunogenic response. remodeling response induced by collectively compensate limitations immunotherapy significantly enhance antitumor checkpoint inhibitor αPD-1. This study proposes perspective therapy cancer.

Language: Английский

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Chemical Design of Magnetic Nanomaterials for Imaging and Ferroptosis-Based Cancer Therapy

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Ferroptosis, an iron-dependent form of regulatory cell death, has garnered significant interest as a therapeutic target in cancer treatment due to its distinct characteristics, including lipid peroxide generation and redox imbalance. However, clinical application oncology is currently limited by issues such suboptimal efficacy potential off-target effects. The advent nanotechnology provided new way for overcoming these challenges through the development activatable magnetic nanoparticles (MNPs). These innovative MNPs are designed improve specificity ferroptosis induction. This Review delves into chemical biological principles guiding design ferroptosis-based therapies imaging-guided therapies. It discusses mechanisms attributes ferroptosis, composition MNPs, their mechanism action inducers, integration with advanced imaging techniques monitoring. Additionally, we examine convergence other strategies, chemodynamic therapy, photothermal photodynamic sonodynamic immunotherapy, within context nanomedicine strategies utilizing MNPs. highlights multifunctional surpass limitations conventional treatments, envisioning future drug-resistance-free, precision diagnostics treating recalcitrant cancers.

Language: Английский

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Multifunctional Sr/Se co-doped ZIF-8 nanozyme for chemo/chemodynamic synergistic tumor therapy via apoptosis and ferroptosis

Theranostics, Journal Year: 2024, Volume and Issue: 14(5), P. 1939 - 1955

Published: Jan. 1, 2024

Rationale: Cancer continues to be a significant public health issue.Traditional treatments such as surgery, radiotherapy, and chemotherapy often fall short because of intrinsic issues lack specificity poor drug delivery, leading insufficient concentration at the tumor site and/or potential side effects.Consequently, improving delivery conventional drugs like doxorubicin (DOX) is crucial for their therapeutic efficacy.Successful cancer treatment achieved when regulated cell death (RCD) cells, which includes apoptotic non-apoptotic processes ferroptosis, fundamental successful treatment.The developing field nanozymes holds considerable promise innovative approaches.Methods: A dual-metallic nanozyme system encapsulated with DOX was created, derived from metal-organic frameworks (MOFs), designed combat tumors by depleting glutathione (GSH) concurrently liberating DOX.The initial phase study examined GSH oxidase-mimicking function dimetallic (ZIF-8/SrSe) through enzyme kinetic assays Density Functional Theory (DFT) simulations.Following this, we probed ability ZIF-8/SrSe@DOX release in response microenvironment vitro, alongside examining its anticancer capabilities mechanisms prompting apoptosis or ferroptosis cells.Moreover, established tumor-bearing animal models corroborate anti-tumor effectiveness our complex identify involved ferroptotic pathways implicated.Results: Enzyme analyses demonstrated that ZIF-8/SrSe exhibits substantial oxidase-like activity, effectively oxidizing reduced disulfide (GSSG), while also inhibiting peroxidase 4 (GPX4) solute carrier family 7 member 11 (SLC7A11).This inhibition led an imbalance iron homeostasis, pronounced caspase activation, subsequent induction cells.Additionally, nanoparticles efficiently delivered DOX, causing DNA damage further promoting pathways.Conclusions: This research outlines design novel platform combines chemotherapeutic agents Fenton reaction catalyst, offering promising strategy therapy leverages synergistic effects ferroptosis.

Language: Английский

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Lipid Nanoparticular Codelivery System for Enhanced Antitumor Effects by Ferroptosis–Apoptosis Synergistic with Programmed Cell Death-Ligand 1 Downregulation

ACS Nano, Journal Year: 2024, Volume and Issue: 18(26), P. 17267 - 17281

Published: June 13, 2024

Intrinsic or acquired resistance to chemical drugs severely limits their therapeutic efficacy in cancer treatment. Various intracellular antioxidant molecules, particularly glutathione (GSH), play a crucial role maintaining redox homeostasis by mitigating the overproduced reactive oxygen species (ROS) due rapid cell proliferation. Notably, these antioxidants also eliminate chemical-drug-induced ROS, eventually diminishing cytotoxicity and rendering them less effective. In this study, we combined erastin, GSH biosynthesis inhibitor, with 2'-deoxy-5-fluorouridine 5'-monophosphate sodium salt (FdUMP), an ROS-based drug, effectively disrupt reverse chemotherapy resistance. Therefore, efficient ferroptosis apoptosis were simultaneously induced for enhanced antitumor effects. Additionally, employed small interfering RNA targeting PD-L1 (siPD-L1) as third agent block immune-checkpoint recognition CD8

Language: Английский

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New insights into crosstalk between Nrf2 pathway and ferroptosis in lung disease

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(11)

Published: Nov. 18, 2024

Abstract Ferroptosis is a distinctive process of cellular demise that linked to amino acid metabolism, lipid oxidation, and iron oxidation. The ferroptosis cascade genes, which are closely associated with the onset lung diseases, among regulatory targets nuclear factor erythroid 2-related 2 (Nrf2). Although regulation mostly mediated by Nrf2, precise roles underlying mechanisms Nrf2 in illness remain unclear. This review provides new insights from recent discoveries involving modulation range diseases. It also systematically describes peroxidation, intracellular antioxidant levels, ubiquitination expression FSP1 GPX4. Finally, it summarises active ingredients drugs potential for treatment With overarching aim expediting improvements treatment, this reference novel therapeutic offers suggestions development medications variety disorders.

Language: Английский

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Recent Advances in Nanomaterial‐Mediated Cell Death for Cancer Therapy

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

Abstract Nanomedicine has shown great anticancer potential by disrupting redox homeostasis and increasing the levels of oxidative stress, but therapeutic effect is limited factors including intrinsic self‐protection mechanism tumors. Cancer cell death can be induced exploration different mechanisms, such as apoptosis, pyroptosis, necroptosis, cuproptosis, ferroptosis. The merging nanotechnology with biomedicine provided tremendous opportunities to construct death‐based nanomedicine for innovative cancer therapy. Nanocarriers are not only used targeted delivery inducers, also components induce achieve efficient tumor treatment. This review focuses on seven modalities mediated nanomaterials, ferroptosis, cuprotosis, immunogenic death, autophagy. mechanisms these described in detail, well preparation nanomaterials that them they exert their effects. Finally, this work describes future development based current knowledge related nanomaterials.

Language: Английский

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Multi-pathway copper metabolisms regulation based on an engineered copper/ferrous nanoplatform for enhanced tumor cuproptosis therapy

Colloids and Surfaces B Biointerfaces, Journal Year: 2025, Volume and Issue: unknown, P. 114682 - 114682

Published: April 1, 2025

Language: Английский

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A nanozyme-based drug delivery system to amplify ferroptosis via MET inhibition and photodynamic therapy

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: unknown, P. 156920 - 156920

Published: Oct. 1, 2024

Language: Английский

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Metal-polyphenol nanoplatform facilitates the healing of infected wounds through a combination of bacterial phototherapy and ferroptosis

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: unknown, P. 158108 - 158108

Published: Nov. 1, 2024

Language: Английский

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