Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: 509, P. 161306 - 161306
Published: March 6, 2025
Language: Английский
Advanced Science, Journal Year: 2023, Volume and Issue: 10(33)
Published: Oct. 11, 2023
Abstract A core‐shell‐structured Cu 2 O@Mn 3 O 8 (CMCO) nanozyme is constructed to serve as a tumor microenvironment (TME)‐activated copper ionophore achieve safe and efficient cuproptosis. The Mn shell not only prevents exposure of normal tissues the core reduce systemic toxicity but also exhibits enhanced enzyme‐mimicking activity owing better band continuity near Fermi surface. glutathione oxidase (GSHOx)‐like CMCO depletes (GSH), which diminishes ability chelate ions, thereby exerting inducing cuproptosis in cancer cells. catalase (CAT)‐like catalyzes overexpressed H TME, generating tricarboxylic acid (TCA) cycle enhance More importantly, Fenton‐like reaction based on release ions inactivation peroxidase 4 induced by elimination GSH results ferroptosis, accompanied accumulation lipid peroxidation reactive oxygen species that can cleave stress‐induced heat shock proteins compromise their protective capacity cells further sensitize nanozymes are partially sulfurized hydrogen sulfide colorectal exhibiting excellent photothermal properties activity. mild effect enhances nanozymes, thus high‐efficiency ferroptosis‐boosted‐cuproptosis.
Language: Английский
Citations
51
Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)
Published: Jan. 25, 2024
Abstract Cuproptosis, an emerging form of programmed cell death, has received tremendous attention in cancer therapy. However, the efficacy cuproptosis remains limited by poor delivery efficiency copper ion carriers. Herein, complex nanoparticles (denoted as Cu(I) NP) are developed that can efficiently deliver into cells to induce cuproptosis. NP demonstrate stimulus‐responsive release complexes, which results mitochondrial dysfunction and promotes aggregation lipoylated dihydrolipoamide S‐acetyltransferase (DLAT), leading Notably, not only cuproptosis, but also elicit robust immune responses suppress tumor growth. Overall, this study provides a promising strategy for cuproptosis‐based
Language: Английский
Citations
42
Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)
Published: April 6, 2024
Abstract Cuproptosis is a newly discovered form of programmed cell death significantly depending on the transport efficacy copper (Cu) ionophores. However, existing Cu ionophores, primarily small molecules with short blood half‐life, face challenges in transporting enough amounts ions into tumor cells. This work describes construction carrier‐free nanoparticles (Ce6@Cu NPs), which self‐assembled by coordination 2+ sonosensitizer chlorin e6 (Ce6), facilitating sonodynamic‐triggered combination cuproptosis and ferroptosis. Ce6@Cu NPs internalized U87MG cells induce sonodynamic effect glutathione (GSH) depletion capability, promoting lipid peroxidation eventually inducing Furthermore, + concentration increases as reacts reductive GSH, resulting downregulation ferredoxin‐1 lipoyl synthase. induces oligomerization lipoylated dihydrolipoamide S‐acetyltransferase, causing proteotoxic stress irreversible cuproptosis. possess satisfactory ability to penetrate blood‐brain barrier, significant accumulation orthotopic U87MG‐Luc glioblastoma. The ferroptosis evidenced both vitro vivo minimal side effects. represents promising therapeutic strategy combining cuproptosis, potentially inspiring further research developing logical effective cancer therapies based
Language: Английский
Citations
42
Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(20), P. 13805 - 13816
Published: March 29, 2024
Cuproptosis, a copper-dependent cell death process, has been confirmed to further activate the immune response and mediate resistance. However, hypoxic tumor microenvironment hampers cuproptosis sensitivity suppresses body's antitumor response. Herein, we have successfully immobilized functionalized catalase (CAT) with long single-stranded DNA containing polyvalent CpG sequences through rolling circle amplification (RCA) techniques, obtaining an enzyme-cored spherical nucleic acid nanoplatform (CAT-ecSNA-Cu) deliver copper ions for cuproptosis. The presence of long-stranded DNA-protected CAT enhances mitochondrial respiration by catalyzing conversion H2O2 O2, thereby sensitizing Meanwhile, increased oxygenation expression hypoxia-inducible factor-1 (HIF-1) protein, resulting in alleviation immunosuppressive microenvironment. Of note, induces immunogenic (ICD), which facilitates dendritic (DC) maturation antigen presentation polyCpG-supported Toll-like receptor 9 (TLR9) activation. Furthermore, cuproptosis-induced PD-L1 upregulation cells complements checkpoint blockers (αPD-L1), enhancing immunity. strategy cuproptosis-mediated responses alleviating hypoxia effectively promotes activation proliferation effector T cells, ultimately leading long-term immunity against cancer.
Language: Английский
Citations
38
Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(37)
Published: April 25, 2024
Abstract Cuproptosis and ferroptosis hold great promise for overcoming apoptotic resistance in liver cancer based on their unique metal‐driven cell death modalities. However, insufficient intracellular copper iron concentration, complicated tumor microenvironment (TME), unclear cross‐regulatory mechanisms between cuproptosis ferroptosis, severely restrict the therapeutic performance. Herein, copper‐doped hollow Prussian blue (CHP) nanozymes are rationally designed loading photosensitizer indocyanine green (ICG) O 2 ‐saturated perfluorohexane (PFH), denoted as ‐PFH@CHPI nanoparticles, to induce ferroptosis. In response specific TME, CHP can synergistically catalyze Fenton reactions consume endogenous glutathione, leading accumulation of reactive oxygen species. Upon near‐infrared irradiation, ‐PFH@CHPI‐enabled photothermal effect simultaneously accelerate catalytic trigger release photodynamic therapy promote oxidative stress. Notably, be effectively activated through Cu + ‐mediated dihydrolipoamide S‐acetyltransferase aggregation Fe–S cluster protein loss. Concurrently, tilt redox balance is favorable lipid peroxidation glutathione peroxidase 4 inactivation, resulting an augmented effect. Mechanistically, stress‐boosted jointly disrupt mitochondrial metabolism, which turn exacerbates stress, thus realizing a mutually enhanced This work may provide new guidance utilizing copper/ferrous‐engineering cuproptosis/ferroptosis synergetic therapy.
Language: Английский
Citations
30
Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)
Published: Aug. 16, 2024
Cuproptosis is a newly identified form of cell death induced by excessive copper (Cu) accumulation within cells. Mechanistically, cuproptosis results from Cu-induced aggregation dihydrolipoamide S-acetyltransferase, correlated with the mitochondrial tricarboxylic acid cycle and loss iron–sulfur cluster proteins, ultimately resulting in proteotoxic stress triggering death. Recently, has garnered significant interest tumor research due to its potential as crucial therapeutic strategy against cancer. In this review, we summarized cellular molecular mechanisms relationship other types Additionally, reviewed current drugs or strategies available induce cells, including Cu ionophores, small compounds, nanomedicine. Furthermore, targeted metabolism specific regulatory genes cancer therapy enhance sensitivity cuproptosis. Finally, discussed feasibility targeting overcome chemotherapy immunotherapy resistance suggested future directions. This study that could open new avenues for developing therapy.
Language: Английский
Citations
22
Small, Journal Year: 2024, Volume and Issue: 20(25)
Published: Jan. 14, 2024
Abstract Ferroptosis is a new form of regulated cell death featuring iron‐dependent lipid peroxides accumulation to kill tumor cells. A growing body evidence has shown the potential ferroptosis‐based cancer therapy in eradicating refractory malignancies that are resistant apoptosis‐based conventional therapies. In recent years, studies have reported number ferroptosis inducers can increase vulnerability cells by regulating ferroptosis‐related signaling pathways. Encouraged rapid development ferroptosis‐driven therapies, interdisciplinary fields combine ferroptosis, pharmaceutical chemistry, and nanotechnology focused. First, prerequisites metabolic pathways for briefly introduced. Then, detail emerging designed boost ferroptosis‐induced therapy, including metal complexes, metal‐based nanoparticles, metal‐free nanoparticles summarized. Subsequently, application synergistic strategies with apoptosis other emphasis on use both cuproptosis induce redox dysregulation intracellular bimetallic copper/iron metabolism disorders during treatment discussed. Finally, challenges associated clinical translation future directions potentiating therapies highlighted.
Language: Английский
Citations
20
Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(11)
Published: Nov. 26, 2024
Abstract Regulated cell death (RCD) refers to the form of that can be regulated by various biomacromolecules. Each modalities have their distinct morphological changes and molecular mechanisms. However, intense evidences suggest lipid peroxidation common feature initiates propagates death. Excessive alters property membrane further damage proteins nucleic acids, which is implicated in human pathologies. Here, we firstly review classical chain process peroxidation, clarify current understanding myriad roles mechanisms RCD types. We also discuss how involves diseases such intimate association between peroxidation-driven leveraged develop rational therapeutic strategies.
Language: Английский
Citations
18
ACS Nano, Journal Year: 2024, Volume and Issue: 18(12), P. 9100 - 9113
Published: March 13, 2024
Reactive oxygen species (ROS) mediated tumor cell death is a powerful anticancer strategy. Cuproptosis copper-dependent and ROS-mediated prospective therapy However, the complex microenvironment (TME), low specificity, poor efficiency, lack of imaging capability impair output current cuproptosis drugs. Herein, we designed dual-responsive two-dimensional metal–organic framework (2D MOF) nanotheranostic via coordination self-assembly strategy using Au(III) tetra-(4-pyridyl) porphine (AuTPyP) as ligand copper ions (Cu2+) nodes. The dual-stimulus combined with protonation pyridyl group in AuTPyP deep-penetration ultrasound (US) together triggered controlled release an acidic TME. ultrathin structure (3.0 nm) nanotheranostics promoted process. released Cu2+ was reduced to Cu+ by depleting overexpressed glutathione (GSH) tumor, which not only activated Ferredoxin 1 (FDX1)-mediated but also catalyzed hydrogen peroxide (H2O2) into reactive Fenton-like reaction. Simultaneously, could specifically bind thioredoxin reductase activate redox imbalance cells. These selectively induced significant mitochondrial vacuoles prominent did damage normal fluorescence magnetic resonance (MRI) results verified this target HeLa greatly promote self-enhanced effect chemotherapy/cuproptosis inhibition efficiency. work helped elucidate assembly multiresponsive high-specificity ROS regulation for application therapy.
Language: Английский
Citations
17
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
Citations
7