A Metal Chelation Therapy to Effectively Eliminate Breast Cancer and Intratumor Bacteria While Suppressing Tumor Metastasis by Copper Depletion and Zinc Ions Surge DOI

Yulin Xie,

Junrong Wang, Chunxia Li

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 12, 2024

Abstract The intratumor microbiota results in the immunosuppressive microenvironment and facilitates tumor growth metastasis. However, developing a synergistic therapy with antitumor, antibacterial, antimetastatic effects faces enormous challenges. Here, we propose an innovative metal chelation to effectively eliminate bacteria suppress Different from traditional that only consumes elements, this not eliminates crucial elements for metabolism but also releases new ions antitumor antibacterial properties. Based on high demand copper breast cancer, prepare fibrous therapeutic nanoagent (Zn‐PEN) by chelating chelator D‐Penicillamine (D‐PEN) Zn 2+ . Firstly, Zn‐PEN achieves dual inhibition of oxidative phosphorylation (OXPHOS) glycolysis cancer through depletion activated cGAS‐STING pathway, thus inducing cell death. Secondly, has capability eradicate Fusobacterium nucleatum ( F. ) thereby mitigating its impact microenvironment. Finally, inhibits metastasis multiple routes, including epithelial‐mesenchymal transition (EMT) process, activation elimination Therefore, verify feasibility mediated 4T1 model infected , providing strategy inhibiting

Language: Английский

Glutathione‐Scavenging Celastrol‐Cu Nanoparticles Induce Self‐Amplified Cuproptosis for Augmented Cancer Immunotherapy DOI
Sheng Lü, Yifan Li, Yingjie Yu

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(35)

Published: June 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.

Language: Английский

Citations

42
Carrier‐Free Self‐Assembly Nano‐Sonosensitizers for Sonodynamic‐Amplified Cuproptosis‐Ferroptosis in Glioblastoma Therapy DOI Creative Commons
Yang Zhu,

Xuegang Niu,

Chengyu Ding

et al.

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

35
Metal‐based smart nanosystems in cancer immunotherapy DOI Creative Commons
Ying Luo,

Xiaojing He,

Qianying Du

et al.

Exploration, Journal Year: 2024, Volume and Issue: 4(6)

Published: March 22, 2024

Abstract Metals are an emerging topic in cancer immunotherapy that have shown great potential modulating immunity cycle and promoting antitumor by activating the intrinsic immunostimulatory mechanisms which been identified recent years. The main challenge of metal‐assisted lies fact free metals as ion forms easily cleared during circulation, even cause systemic metal toxicity due to off‐target effects. With rapid development nanomedicine, metal‐based smart nanosystems (MSNs) with unique controllable structure become one most promising delivery carriers solve issue, owing their various endogenous/external stimuli‐responsiveness release ions for metalloimmunotherapy. In this review, state‐of‐the‐art research progress metal‐related is comprehensively summarized. First, mainstream MSNs‐assisted will be delineated. immunological effects certain categorization MSNs different characters compositions then provided, followed representative exemplar applications treatment, synergistic combination immunotherapy. Finally, we conclude review a summary remaining challenges associated provide authors' perspective on further advances.

Language: Английский

Citations

25
The crosstalk between copper-induced oxidative stress and cuproptosis: a novel potential anticancer paradigm DOI Creative Commons
Thi Thuy Tien Vo, Tzu‐Yu Peng,

Thi Hong Nguyen

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 5, 2024

Abstract Copper is a crucial trace element that plays role in various pathophysiological processes the human body. also acts as transition metal involved redox reactions, contributing to generation of reactive oxygen species (ROS). Under prolonged and increased ROS levels, oxidative stress occurs, which has been implicated different types regulated cell death. The recent discovery cuproptosis, copper-dependent death pathway distinct from other known forms, raised interest researchers field cancer therapy. Herein, present work aims outline current understanding with an emphasis on its anticancer activities through interplay copper-induced stress, thereby providing new ideas for therapeutic approaches targeting modes future.

Language: Английский

Citations

25
A cuproptosis-based nanomedicine suppresses triple negative breast cancers by regulating tumor microenvironment and eliminating cancer stem cells DOI
Chen Xiao, Xing Wang, Shiyou Li

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 313, P. 122763 - 122763

Published: Aug. 17, 2024

Language: Английский

Citations

17
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
Infinite Coordination Polymer Polydopamine Nanocomposites Dual‐Pathway Multistep Induction of Long‐Term Hyperimmunity Combined With Photothermal‐Chemo Synergistic Therapy Colorectal Cancer DOI Creative Commons
Xiaojiang Zhang, Yujie Zhang, Pengqian Wang

et al.

Aggregate, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 5, 2025

ABSTRACT To improve the long‐term therapeutic efficacy of colorectal cancer, we propose a synergistic treatment strategy involving dual‐pathway, multistep induction hyperimmunity combined with photothermal‐chemotherapy. implement this strategy, infinite coordination polymer nanoparticles (SN38‐Mn(II)‐EGCG ICP NPs) were prepared by coordinating SN38, EGCG, and Mn 2+ . These then coated polydopamine (PDA) grafted folate‐PEG‐thiol (FA‐PEG‐SH) onto their surfaces, producing tumor‐targeting folate‐modified PDA nanocomposites (ICP@FA‐PDA nanocomposites). exhibit particle size 94.9 ± 1.6 nm high drug loading capacity (83.3% 1.5%), release under acidic conditions while maintaining stability in physiological environments. Furthermore, each component within serves multiple functions. Notably, incorporation components triggers powerful antitumor immune effect establishes enduring memory through dual‐pathway approach, which is produced activation cGAS‐STING pathway immunogenic cell death (ICD) four‐component process. Under low‐dose regimen, approach induces generates ultra‐long immunological memory, marked ninefold increase CD8 + T infiltration, fourfold CD4 lymphocytes, reduction Treg cells, fivefold cells. The remarkable therapy achieved combination SN38 EGCG chemotherapy photothermal therapy. In vivo studies demonstrated that mice treated ICP@FA‐PDA complete eradication cancer 21 days, no recurrence observed 60 days. hold significant promise potential for future clinical translation.

Language: Английский

Citations

2
Copper‐Based Bio‐Coordination Nanoparticle for Enhanced Pyroptosis‐Cuproptosis Cancer Immunotherapy through Redox Modulation and Glycolysis Inhibition DOI Open Access

Ju‐E Cun,

Ziyun He,

Fan Xi

et al.

Small, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 5, 2025

Copper-based nanoparticles have garnered significant interest in cancer therapy due to their ability induce oxidative stress and cuproptosis cells. However, antitumor effectiveness is constrained by the dynamic redox balance metabolic shift between phosphorylation glycolysis. Here, a polydopamine-coated copper-α-ketoglutaric acid (α-KG) coordination polymer nanoparticle (CKPP) designed for combined pyroptosis-cuproptosis immunotherapy amplifying reactive oxygen species (ROS) production regulating cellular metabolism. The intracellular imbalance achieved through synergistic effects of α-KG-induced mitochondrial reprogramming, photothermally enhanced superoxide dismutase-like activity polydopamine, glutathione depletion copper ions. multifaceted modulation results substantial increase ROS levels, triggering subsequent pyroptosis Furthermore, α-KG shifts metabolism from glycolysis phosphorylation, thereby enhancing induced combination dyshomeostasis inhibition potent enhancement pyroptosis-cuproptosis-mediated therapy. In murine model colorectal cancer, CKPP exhibited remarkable anticancer effect, achieving tumor rate 96.3% complete eradication two out five cases. Overall, this bio-engineered metal-organic nanocomposite demonstrates potential treating immunotherapy.

Language: Английский

Citations

2
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

Citations

15
Multifunctional Copper‐Phenolic Nanopills Achieve Comprehensive Polyamines Depletion to Provoke Enhanced Pyroptosis and Cuproptosis for Cancer Immunotherapy DOI
Guo‐Qing Zhu, Yulin Xie, Junrong Wang

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(45)

Published: Sept. 17, 2024

Abstract The overexpression of polyamines in tumor cells contributes to the establishment immunosuppressive microenvironment and facilitates growth. Here, it have ingeniously designed multifunctional copper‐piceatannol/HA nanopills (Cu‐Pic/HA NPs) that effectively cause total intracellular depletion by inhibiting synthesis, depleting polyamines, impairing uptake, resulting enhanced pyroptosis cuproptosis, thus activating a powerful immune response achieve anti‐tumor therapy. Mitochondrial dysfunction from overall not only leads surge copper ions mitochondria, thereby causing aggregation toxic proteins induce but also triggers accumulation reactive oxygen species (ROS) within which further upregulates expression zDHHC5 zDHHC9 promote palmitoylation gasdermin D (GSDMD) GSDMD‐N, ultimately inducing pyroptosis. Then occurrence cuproptosis is conductive remodel microenvironment, responses growth metastasis. This therapeutic strategy through comprehensive provides novel template for cancer immunotherapy.

Language: Английский

Citations

15