Cuproptosis: A novel therapeutic target for overcoming cancer drug resistance

Drug Resistance Updates, Год журнала: 2023, Номер 72, С. 101018 - 101018

Опубликована: Ноя. 11, 2023

Cuproptosis is a newly identified form of cell death driven by copper. Recently, the role copper and triggered in pathogenesis cancers have attracted attentions. has garnered enormous interest cancer research communities because its great potential for therapy. Copper-based treatment exerts an inhibiting tumor growth may open door chemotherapy-insensitive tumors. In this review, we provide critical analysis on homeostasis dysregulation development progression cancers. Then core molecular mechanisms cuproptosis discussed, followed summarizing current understanding copper-based agents (copper chelators, ionophores, complexes-based dynamic therapy) treatment. Additionally, summarize emerging data ionophores to subdue chemotherapy resistance different types We also review small-molecule compounds nanoparticles (NPs) that kill cells inducing cuproptosis, which will shed new light anticancer drugs through future. Finally, important concepts pressing questions future should be focused were discussed. This article suggests targeting could novel antitumor therapy strategy overcome drug resistance.

Язык: Английский

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Cuproptosis: Harnessing Transition Metal for Cancer Therapy

ACS Nano, Год журнала: 2023, Номер 17(20), С. 19581 - 19599

Опубликована: Окт. 11, 2023

Transition metal elements, such as copper, play diverse and pivotal roles in oncology. They act constituents of metalloenzymes involved cellular metabolism, function signaling molecules to regulate the proliferation metastasis tumors, are integral components metal-based anticancer drugs. Notably, recent research reveals that excessive copper can also modulate occurrence programmed cell death (PCD), known cuprotosis, cancer cells. This modulation occurs through disruption tumor metabolism induction proteotoxic stress. discovery uncovers a mode interaction between transition metals proteins, emphasizing intricate link homeostasis metabolism. Moreover, they provide innovative therapeutic strategies for precise diagnosis treatment malignant tumors. At crossroads chemistry oncology, we undertake comprehensive review elucidating molecular mechanisms underpinning cuproptosis. Additionally, summarize current nanotherapeutic approaches target cuproptosis an overview available laboratory clinical methods monitoring this process. In context emerging concepts, challenges, opportunities, emphasize significant potential nanotechnology advancement field.

Язык: Английский

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Nanozyme-mediated biocatalysis as a mitochondrial oxidative stress amplifier for tumor nanocatalytic immunotherapy

Chemical Engineering Journal, Год журнала: 2023, Номер 481, С. 148270 - 148270

Опубликована: Дек. 23, 2023

Язык: Английский

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Copper homeostasis and cuproptosis in cancer immunity and therapy

Immunological Reviews, Год журнала: 2023, Номер 321(1), С. 211 - 227

Опубликована: Сен. 16, 2023

Summary Copper is an essential nutrient for maintaining enzyme activity and transcription factor function. Excess copper results in the aggregation of lipoylated dihydrolipoamide S‐acetyltransferase (DLAT), which correlates to mitochondrial tricarboxylic acid (TCA) cycle, resulting proteotoxic stress eliciting a novel cell death modality: cuproptosis. Cuproptosis exerts indispensable role cancer progression, considered promising strategy therapy. Cancer immunotherapy has gained extensive attention owing breakthroughs immune checkpoint blockade; furthermore, cuproptosis strongly connected modulation antitumor immunity. Thus, thorough recognition concerning mechanisms involved metabolism may facilitate improvement management. This review outlines cellular molecular characteristics links regulated modality with human cancers. We also current knowledge on complex effects immunity response. Furthermore, potential agents that elicit pathways are summarized. Lastly, we discuss influence induction tumor microenvironment as well challenges adding regulators therapeutic strategies beyond traditional

Язык: Английский

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Crosstalk between ferroptosis and cuproptosis: From mechanism to potential clinical application

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 171, С. 116115 - 116115

Опубликована: Янв. 5, 2024

Ferroptosis and cuproptosis, regulated forms of cell death resulting from metal ion accumulation, are closely related in terms occurrence, metabolism, signaling pathways, drug resistance. Notably, it is now understood that these processes play crucial roles regulating physiological pathological processes, especially tumor development. Consequently, ferroptosis cuproptosis have gained increasing significance as potential targets for anti-cancer This article systematically outlines the molecular mechanisms cross-talk components both elucidating their impacts on cancer. Furthermore, investigates clinical perspective targeted cancer chemotherapy, immunotherapy, radiotherapy. Our discussion extends to a comparative analysis nanoparticles developed based cancer, contrasting them with current conventional therapies. Opportunities challenges treatment explored, emphasizing therapeutic direction co-targeting cuproptosis. The also attempts analyze applications this approach while summarizing existing barriers require overcoming.

Язык: Английский

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Glutathione‐Scavenging Celastrol‐Cu Nanoparticles Induce Self‐Amplified Cuproptosis for Augmented Cancer Immunotherapy

Advanced Materials, Год журнала: 2024, Номер 36(35)

Опубликована: Июнь 27, 2024

Cuproptosis is a novel copper-dependent programmed cell death. The efficacy of cuproptosis highly dependent on intracellular copper accumulation and counteracted by high level glutathione (GSH) in tumor cells. Here, this work develops self-amplified nanoparticles (Cel-Cu NP) using celastrol (Cel), natural product isolated from medical plant. In Cel-Cu NP, Cel serves as versatile ionophore, exhibiting an ideal coordination capacity toward ions without compromising the induction. Notably, can simultaneously scavenge GSH content to amplify cuproptosis. Moreover, further activates immunogenic death (ICD) elicit robust immune response. Combining with checkpoint blockade, NP effectively eradicates metastatic tumors mouse lung metastasis model. This study provides efficient nanomedicine inducing for immunotherapy.

Язык: Английский

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Biomimetic Nano-Drug Delivery System: An Emerging Platform for Promoting Tumor Treatment

International Journal of Nanomedicine, Год журнала: 2024, Номер Volume 19, С. 571 - 608

Опубликована: Янв. 1, 2024

Abstract: With the development of nanotechnology, nanoparticles (NPs) have shown broad prospects as drug delivery vehicles. However, they exhibit certain limitations, including low biocompatibility, poor physiological stability, rapid clearance from body, and nonspecific targeting, which hampered their clinical application. Therefore, novel systems with improved biocompatibility high target specificity remains a major challenge. In recent years, biofilm mediated biomimetic nano-drug system (BNDDS) has become research hotspot focus in field life sciences. This new platform uses bio-nanotechnology to encapsulate synthetic NPswithin membrane, organically integrating immunogenicity, toxicity, tumor good adjustability versatility nanocarrier, shows promising applications precision therapy. this review, we systematically summarize progress BNDDS used for optimizing delivery, providing theoretical reference designing safe efficient treatment strategies improve outcomes. Keywords: nanoparticles, cell targeted therapy

Язык: Английский

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Carrier‐Free Self‐Assembly Nano‐Sonosensitizers for Sonodynamic‐Amplified Cuproptosis‐Ferroptosis in Glioblastoma Therapy

Advanced Science, Год журнала: 2024, Номер 11(23)

Опубликована: Апрель 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

Язык: Английский

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Enzyme Core Spherical Nucleic Acid That Enables Enhanced Cuproptosis and Antitumor Immune Response through Alleviating Tumor Hypoxia

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(20), С. 13805 - 13816

Опубликована: Март 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.

Язык: Английский

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Self‐Reinforced Bimetallic Mito‐Jammer for Ca²⁺ Overload‐Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization

Advanced Science, Год журнала: 2024, Номер 11(15)

Опубликована: Фев. 11, 2024

Abstract Overproduction of reactive oxygen species (ROS), metal ion accumulation, and tricarboxylic acid cycle collapse are crucial factors in mitochondria‐mediated cell death. However, the highly adaptive nature damage‐repair capabilities malignant tumors strongly limit efficacy treatments based on a single treatment mode. To address this challenge, self‐reinforced bimetallic Mito‐Jammer is developed by incorporating doxorubicin (DOX) calcium peroxide (CaO 2 ) into hyaluronic (HA) ‐modified metal‐organic frameworks (MOF). After cellular, dissociates CaO Cu 2+ tumor microenvironment. The exposed further yields hydrogen (H O Ca weakly acidic environment to strengthen ‐based Fenton‐like reaction. Furthermore, combination chemodynamic therapy overload exacerbates ROS storms mitochondrial damage, resulting downregulation intracellular adenosine triphosphate (ATP) levels blocking Cu‐ATPase sensitize cuproptosis. This multilevel interaction strategy also activates robust immunogenic death suppresses metastasis simultaneously. study presents multivariate model for revolutionizing mitochondria relying continuous retention ions boost cuproptosis/immunotherapy cancer.

Язык: Английский

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