PEGylated Elesclomol@Cu(Ⅱ)-based Metal‒organic Framework with Effective Nanozyme Performance and Cuproptosis Induction Efficacy for Enhanced PD-L1-based Immunotherapy DOI Creative Commons
Xufeng Lu,

Wenhai Deng,

Shuaibin Wang

et al.

Materials Today Bio, Journal Year: 2024, Volume and Issue: 29, P. 101317 - 101317

Published: Oct. 30, 2024

Language: Английский

A Self‐Amplifying ROS‐Responsive Nanoplatform for Simultaneous Cuproptosis and Cancer Immunotherapy DOI Creative Commons
Hangyi Wu, Zhenhai Zhang, Yanni Cao

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)

Published: April 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

Language: Английский

Citations

42
Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives DOI Creative Commons
Chenliang Zhang, Tingting Huang, Liping Li

et al.

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

16
Advances in cuproptosis harnessing copper-based nanomaterials for cancer therapy DOI
Yuanying Yang, Chen Dong, Xuehua Ma

et al.

Journal of Materials Chemistry B, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

Citations

2
Redox-manipulating nanocarriers for anticancer drug delivery: a systematic review DOI Creative Commons
Xuan Meng,

Yongli Shen,

Huanyu Zhao

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 28, 2024

Language: Английский

Citations

14
The Role of Copper Ions in Mediating the Anti‐Cancer Effects Using Nanomaterials DOI Open Access

Irfan Mehmud,

Song Wu, Shaohua Zhang

et al.

Advanced Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

Citations

1
Single-atom–doped piezocatalyst induces copper-free cuproptosis in tumor therapy DOI Creative Commons
M. Zhang, Xinran Song, Yu Qin

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(7)

Published: Feb. 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

Language: Английский

Citations

1
Metal ion interference therapy: metal-based nanomaterial-mediated mechanisms and strategies to boost intracellular “ion overload” for cancer treatment DOI
Yutang Li, Yandong Wang, Zhao Li

et al.

Materials Horizons, Journal Year: 2024, Volume and Issue: 11(18), P. 4275 - 4310

Published: Jan. 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.

Language: Английский

Citations

7
Mitochondria‐Targeted Multifunctional Nanoparticles Combine Cuproptosis and Programmed Cell Death‐1 Downregulation for Cancer Immunotherapy DOI Creative Commons
Youyou Li, Jing Liu, Ralph R. Weichselbaum

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 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.

Language: Английский

Citations

7
Reactive Oxygen Species-Responsive Pillararene-Embedded Covalent Organic Frameworks with Amplified Antimicrobial Photodynamic Therapy for the Targeted Elimination of Periodontitis Pathogens DOI
Shuang Liang, Menghao Li, Manlin Qi

et al.

Nano Letters, Journal Year: 2024, Volume and Issue: 24(43), P. 13708 - 13717

Published: Oct. 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.

Language: Английский

Citations

7
Polyvalent Aptamer Nanodrug Conjugates Enable Efficient Tumor Cuproptosis Therapy Through Copper Overload and Glutathione Depletion DOI
Shuang Wang, Xueliang Liu,

Dali Wei

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(44), P. 30033 - 30045

Published: Oct. 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.

Language: Английский

Citations

7