Cuproptosis: Advances in Stimulus‐Responsive Nanomaterials for Cancer Therapy DOI

Jiacheng Lu,

Yuqing Miao, Yuhao Li

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(19)

Published: April 15, 2024

Abstract Cuproptosis, a recently identified non‐apoptotic programmed cell death modality, attracts considerable attention in the realm of cancer therapeutics owing to its unique cellular demise mechanisms. Since initial report 2022, strategies inducing or amplifying cuproptosis for treatment emerge. The engineering nano‐systems elicit effectively circumvents constraints associated with conventional small‐molecule pharmaceutical interventions, presenting novel prospects oncological therapy. Stimulus‐responsive nanomaterials, leveraging their distinctive spatiotemporal control attributes, are investigated role modulating induction augmentation cuproptosis. In this comprehensive review, physiological characteristics cuproptosis, encompassing facets such as copper overload and depletion, coupled regulatory factors intrinsic expounded upon. Subsequently, design methodologies stimulus‐responsive enhancement employing stimuli light, ultrasound, X‐ray, tumor microenvironment, systematically delineated. This review encompasses intricacies nanomaterial design, insights into therapeutic processes, advantages. Finally, challenges inherent induction/enhancement deliberated upon prospective future trajectory copper‐mediated therapy provided.

Language: Английский

Enzyme Core Spherical Nucleic Acid That Enables Enhanced Cuproptosis and Antitumor Immune Response through Alleviating Tumor Hypoxia DOI
Yuting Huang, Xueliang Liu, Jiawei Zhu

et al.

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

36
Self‐Reinforced Bimetallic Mito‐Jammer for Ca2+ Overload‐Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization DOI Creative Commons

Chier Du,

Xun Guo,

Xiaoling Qiu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(15)

Published: Feb. 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.

Language: Английский

Citations

35
Microfluidic Synthesis of CuH Nanoparticles for Antitumor Therapy through Hydrogen-Enhanced Apoptosis and Cuproptosis DOI

Guanzhong He,

Yongchun Pan,

Fei Zeng

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(12), P. 9031 - 9042

Published: March 12, 2024

Cuproptosis has drawn enormous attention in antitumor material fields; however, the responsive activation of cuproptosis against tumors using nanomaterials with high atom utilization is still challenging. Herein, a copper-based nanoplatform consisting acid-degradable copper hydride (CuH) nanoparticles was developed via microfluidic synthesis. After coating tumor-targeting hyaluronic acid (HA), denoted as HA-CuH-PVP (HCP) shows conspicuous damage toward tumor cells by generating Cu+ and hydrogen (H2) simultaneously. can induce apoptosis relying on Fenton-like reactions lead to causing mitochondrial protein aggregation. Besides, existence H2 enhance both cell death types dysfunction intracellular redox homeostatic disorders. In vivo experimental results further exhibit desirable potential HCP for killing inhibiting lung metastases, which will broaden horizons designing materials triggering better efficacy.

Language: Английский

Citations

29
Biomimetic copper-doped polypyrrole nanoparticles induce glutamine metabolism inhibition to enhance breast cancer cuproptosis and immunotherapy DOI
Ni Zhang, Ping Wei,

Kexiang Rao

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 371, P. 204 - 215

Published: May 31, 2024

Language: Английский

Citations

21
An Intelligent Cupreous Nanoplatform with Self-Supplied H2O2 and Cu2+/Cu+ Conversion to Boost Cuproptosis and Chemodynamic Combined Therapy DOI

Xiangjie Tian,

Hui Xu, Fangfang Zhou

et al.

Chemistry of Materials, Journal Year: 2024, Volume and Issue: 36(2), P. 815 - 828

Published: Jan. 11, 2024

Cuproptosis is a newly identified copper-dependent cell death and holds great promise for cancer therapy. However, transporting enough copper into cells challenge. Herein, an intelligent cupreous nanoplatform (denoted as CuO2-MSN@TA-Cu2+), consisting of in situ formation CuO2 within mesoporous silica nanoparticles (MSN) then deposition with tannic acid (TA)-Cu2+ complex, designed developed to realize on-demand delivery cuproptosis-based combination CuO2-MSN@TA-Cu2+ exhibits tumor microenvironment-triggered therapeutic activity, wherein the outer TA-Cu2+ complex readily disassembled release Cu2+ liberate internal produce H2O2. The overloaded can not only directly convert endogenous H2O2 self-supplied highly toxic hydroxyl radicals chemodynamic therapy (CDT) via Cu-based Fenton-like reaction but also undergo glutathione-mediated reduction Cu+ species induce potent cellular cuproptosis enhance CDT. experimental results indicate that produces remarkable cytotoxicity against significantly suppresses growth by 93.42% mice-bearing 4T1 breast tumors. This work provides new paradigm boost cuproptosis-related may inspire design advanced nanoplatforms.

Language: Английский

Citations

20
Inhalable metal–organic framework-mediated cuproptosis combined with PD-L1 checkpoint blockade for lung metastasis synergistic immunotherapy DOI Creative Commons

Chongzheng Yan,

Y Liu, Guozhi Zhao

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(5), P. 2281 - 2297

Published: Feb. 6, 2024

Cuproptosis shows enormous application prospects in lung metastasis treatment. However, the glycolysis, Cu+ efflux mechanisms, and insufficient drug accumulation severely restrict cuproptosis efficacy. Herein, an inhalable poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate) (OPDEA)-coated copper-based metal–organic framework encapsulating pyruvate dehydrogenase kinase 1 siRNA (siPDK) is constructed for mediating subsequently promoting immunotherapy, namely OMP. After inhalation, OMP highly efficient long-term retention, ascribing to OPDEA-mediated pulmonary mucosa penetration. Within tumor cells, degraded release Cu2+ under acidic condition, which will be reduced toxic induce glutathione (GSH) regulation. Meanwhile, siPDK released from inhibits intracellular glycolysis adenosine-5ʹ-triphosphate (ATP) production, then blocking protein ATP7B, thereby rendering cells more sensitive OMP-mediated cuproptosis. Moreover, triggers immunogenic cell death (ICD) promote dendritic (DCs) maturation CD8+ T infiltration. Notably, OMP-induced up-regulates membrane-associated programmed death-ligand (PD-L1) expression induces soluble PD-L1 secretion, thus synergizes with anti-PD-L1 antibodies (aPD-L1) reprogram immunosuppressive microenvironment, finally yielding improved immunotherapy Overall, may serve as nanoplatform afford preferable efficacy against through inducing combining aPD-L1.

Language: Английский

Citations

18
Sono‐Triggered Cascade Lactate Depletion by Semiconducting Polymer Nanoreactors for Cuproptosis‐Immunotherapy of Pancreatic Cancer DOI

Ningyue Yu,

Jianhui Zhou,

Mengbin Ding

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(30)

Published: May 6, 2024

Abstract The high level of lactate in tumor microenvironment not only promotes development and metastasis, but also induces immune escape, which often leads to failures various therapy strategies. We here report a sono‐triggered cascade depletion strategy by using semiconducting polymer nanoreactors (SPN LCu ) for cancer cuproptosis‐immunotherapy. SPN mainly contain as sonosensitizer, oxidase (LOx) conjugated via reactive oxygen species (ROS)‐cleavable linker chelated Cu 2+ . Upon ultrasound (US) irradiation, the generates singlet ( 1 O 2 cut ROS‐cleavable allow release LOx that catalyzes produce hydrogen peroxide (H ). will be reduced + microenvironment, reacts with produced H obtain hydroxyl radical (⋅OH) further improves destroying linkers. As such, achieves effective depletion, thus relieving immunosuppressive roles lactate. Moreover, toxic cuproptosis cause immunogenic cell death (ICD) activating antitumor immunological effect. are used treat both subcutaneous deep‐tissue orthotopic pancreatic observably enhanced efficacy restricting growths. This study provides precise tactic therapy.

Language: Английский

Citations

18
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

18
Nanotechnology-based biomedical devices in the cancer diagnostics and therapy DOI
Junaid Tantray, Akhilesh Patel,

Hiba Parveen

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(2)

Published: Jan. 20, 2025

Language: Английский

Citations

2
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