A Self‐Amplifying ROS‐Responsive Nanoplatform for Simultaneous Cuproptosis and Cancer Immunotherapy

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

Опубликована: Апрель 3, 2024

Abstract Cuproptosis is an emerging cell death pathway that depends on the intracellular Cu ions. Elesclomol (ES) as efficient ionophore can specifically transport into mitochondria and trigger cuproptosis. However, ES be rapidly removed metabolized during intravenous administration, leading to a short half‐life limited tumor accumulation, which hampers its clinical application. Here, study develops reactive oxygen species (ROS)‐responsive polymer (PCP) based cinnamaldehyde (CA) polyethylene glycol (PEG) encapsulate ES‐Cu compound (EC), forming ECPCP. ECPCP significantly prolongs systemic circulation of EC enhances accumulation. After cellular internalization, PCP coating stimulatingly dissociates exposing high‐level ROS, releases Cu, thereby triggering via Meanwhile, 2+ ‐stimulated Fenton‐like reaction together with CA‐stimulated ROS production simultaneously breaks redox homeostasis, compensates for insufficient oxidative stress treated alone, in turn inducing immunogenic cells, achieving simultaneous cuproptosis immunotherapy. Furthermore, excessive accelerates stimuli‐dissociation ECPCP, positive feedback therapy loop against self‐alleviation. Therefore, nanoplatform immunotherapy improves dual antitumor mechanism provides potential optimization

Язык: Английский

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Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Авг. 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.

Язык: Английский

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Redox-manipulating nanocarriers for anticancer drug delivery: a systematic review

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Сен. 28, 2024

Язык: Английский

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Polyvalent Aptamer Nanodrug Conjugates Enable Efficient Tumor Cuproptosis Therapy Through Copper Overload and Glutathione Depletion

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(44), С. 30033 - 30045

Опубликована: Окт. 28, 2024

Cuproptosis, a recently identified form of copper-dependent cell death, shows promising tumor suppressive effects with minimal drug resistance. However, its therapeutic efficacy is hampered by dependence on copper ions and the glutathione (GSH)-rich microenvironment in tumors. Here, we have developed polyvalent aptamer nanodrug conjugates (termed CuPEs@PApt) nucleosome-like structure to improve cuproptosis therapy exploiting mitochondrial overload GSH depletion. Polyvalent (PApt), comprising epithelial adhesion molecule aptamers for targeting repetitive PolyT sequences chelation, facilitates efficient loading targeted delivery peroxide-Elesclomol nanodots (CuPEs). Upon internalization cells, Elesclomol released from CuPEs@PApt accumulates mitochondria initiate cuproptosis, while lysosomal degradation CuP generates exogenous Cu2+ H2O2, triggering Fenton-like reaction depletion enhance cuproptosis. In vitro vivo experiments confirm this strategy inducing immunogenic latter contributing activation antitumor immune response synergistic growth inhibition.

Язык: Английский

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Metal ion interference therapy: metal-based nanomaterial-mediated mechanisms and strategies to boost intracellular “ion overload” for cancer treatment

Materials Horizons, Год журнала: 2024, Номер 11(18), С. 4275 - 4310

Опубликована: Янв. 1, 2024

This comprehensive review systematically summarizes the intrinsic mechanism of different metal ion (such as Fe 3+ /Fe 2+ , Cu /Cu + Ca Zn Mn Na /K and Mg )-mediated interference therapies their research progress in cancer treatment.

Язык: Английский

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Mitochondria‐Targeted Multifunctional Nanoparticles Combine Cuproptosis and Programmed Cell Death‐1 Downregulation for Cancer Immunotherapy

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Июль 16, 2024

The combination of cuproptosis and immune checkpoint inhibition has shown promise in treating malignant tumors. However, it remains a challenge to deliver copper ions inhibitors efficiently simultaneously Herein, mitochondria-targeted nanoscale coordination polymer particle, Cu/TI, comprising Cu(II), triphenylphosphonium conjugate 5-carboxy-8-hydroxyquinoline (TI), for effective induction programmed cell death-1 (PD-L1) downregulation is reported. Upon systemic administration, Cu/TI accumulates tumor tissues induce immunogenic cancer death reduce PD-L1 expression. Consequently, promotes the intratumoral infiltration activation cytotoxic T lymphocytes greatly inhibit progression colorectal carcinoma triple-negative breast mouse models without causing obvious side effects.

Язык: Английский

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Advances in cuproptosis harnessing copper-based nanomaterials for cancer therapy

Journal of Materials Chemistry B, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

This review discusses the recent developments in copper-based nanomaterials that utilize copper-induced cell death, categorized by materials systems, while highlighting limitations of current cuproptosis related nanomaterials.

Язык: Английский

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The Role of Copper Ions in Mediating the Anti‐Cancer Effects Using Nanomaterials

Advanced Therapeutics, Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

Abstract Copper plays a pivotal role in human physiology, particularly oncology, acting both as facilitator of progression and also potential avenue for advanced therapeutic approaches. Maintaining copper homeostasis is crucial. The dysregulation implicated tumor growth through its involvement critical processes angiogenesis, proliferation, metastasis. elevation level the microenvironment (TME) activates oncogenic pathways to drive neovascularization sustained malignancies. However, same reliance on offers unique weakness that can be leveraged innovative interventions. recent advances nanomedicine enable synthesis nanostructures help modulate with precision offering multifaceted approaches copper‐based cancer therapy controlled release mechanism, optimized structures induce cuproptosis, selective eradication cells minimum systemic toxicity. This review explores dual biology, emphasizing contribution tumors emerging application targeted therapy. highlights harnessing therapies their transformative from bench bed side novel, highly effective, clinical safety.

Язык: Английский

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Single-atom–doped piezocatalyst induces copper-free cuproptosis in tumor therapy

Science Advances, Год журнала: 2025, Номер 11(7)

Опубликована: Фев. 14, 2025

Cuproptosis, a distinct cell death pathway, has been integrated into nanomedicine for disease theranostics. However, current nanosystems inducing cuproptosis rely on exogenous toxic copper ions, limiting the scope of biomaterials. Developing nanoplatforms that induce without holds substantial promise. Here, we engineered two-dimensional iron (Fe) single-atom–doped molybdenum disulfide (MoS 2 ) piezocatalyst (Fe-MoS tumor therapy. Incorporating single Fe atoms enhances MoS piezoelectric polarization via charge redistribution and modulates Mo oxidation states, enabling multifaceted enzymatic activities, including peroxidase-, glutathione oxidase–, oxidase-, catalase-like activities. Upon ultrasound stimulation, Fe-MoS nanocatalyst generates reactive oxygen species depletes synergistic piezocatalytic enzyocatalytic effects, disrupting ion homeostasis cuproptosis, concurrently triggering ferroptosis ferritinophagy, which collectively suppression. This study represents first paradigm to introduce copper-free initiating substantially advancing applications in

Язык: Английский

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Reactive Oxygen Species-Responsive Pillararene-Embedded Covalent Organic Frameworks with Amplified Antimicrobial Photodynamic Therapy for the Targeted Elimination of Periodontitis Pathogens

Nano Letters, Год журнала: 2024, Номер 24(43), С. 13708 - 13717

Опубликована: Окт. 17, 2024

Reactive oxygen species (ROS)-responsive drug delivery systems possess immense potential for targeted and controlled release of therapeutics. However, the rapid responsiveness to ROS sustained antibacterial drugs are often limited by challenging microenvironment periodontitis. Integrating ROS-responsive with photocatalytic technologies presents a strategic approach overcome these limitations. Herein, pillararene-embedded covalent organic framework (PCOF) incorporating prodrug thioacetal (TA) has been developed treat This drug-loaded nanoplatform, namely TA-loaded PCOF, utilizes self-amplifying property enhance therapeutic efficacy. PCOFs demonstrate exceptional photosensitivity generation capabilities when employed as carriers. When exposed ROS, TA within nanoplatform was activated cleaved into cinnamaldehyde (CA), highly potent compound. By leveraging visible light activate site-specific infection targeting, PCOF effectively alleviated periodontitis, thereby advancing field systems.

Язык: Английский

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