Digitonin‐Loaded Nanoscale Metal–Organic Framework for Mitochondria‐Targeted Radiotherapy‐Radiodynamic Therapy and Disulfidptosis DOI Creative Commons
Wenyao Zhen, Yingjie Fan, Tomas Germanas

et al.

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

Published: Sept. 10, 2024

Abstract The efficacy of radiotherapy (RT) is limited by inefficient X‐ray absorption and reactive oxygen species generation, upregulation immunosuppressive factors, a reducing tumor microenvironment (TME). Here, the design mitochondria‐targeted digitonin (Dig)‐loaded nanoscale metal‐organic framework, Th‐Ir‐DBB/Dig, reported to overcome these limitations elicit strong antitumor effects upon low‐dose irradiation. Built from Th 6 O 4 (OH) secondary building units (SBUs) photosensitizing Ir(DBB)(ppy) 2 2+ (Ir‐DBB, DBB = 4,4′‐di(4‐benzoato)−2,2′‐bipyridine; ppy 2‐phenylpyridine) ligands, Th‐Ir‐DBB exhibits RT‐radiodynamic therapy (RDT) via potent radiosensitization with high‐Z SBUs for hydroxyl radical generation efficient excitation Ir‐DBB ligands singlet production. Th‐Ir‐DBB/Dig releases in acidic TMEs trigger disulfidptosis cancer cells sensitize RT‐RDT through glucose glutathione depletion. released simultaneously downregulates multiple immune checkpoints T cholesterol As result, Th‐Ir‐DBB/dig plus irradiation induces immunity effectively inhibit growth mouse models colon breast cancer.

Language: Английский

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

48
A strategy of “adding fuel to the flames” enables a self-accelerating cycle of ferroptosis-cuproptosis for potent antitumor therapy DOI
Lin Huang,

Jiaoyang Zhu,

Guochao Wu

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 311, P. 122701 - 122701

Published: July 6, 2024

Language: Английский

Citations

30
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

24
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

21
Metal–Organic Framework-Based Nanovaccine for Relieving Immunosuppressive Tumors via Hindering Efferocytosis of Macrophages and Promoting Pyroptosis and Cuproptosis of Cancer Cells DOI
Yang Liu, Rui Niu, Xiaodong Zhang

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(19), P. 12386 - 12400

Published: May 3, 2024

Current cancer vaccines face challenges due to an immunosuppressive tumor microenvironment and their limited ability produce effective immune response. To address the above limitations, we develop a 3-(2-spiroadamantyl)-4-methoxy-4-(3-phosphoryloxy)-phenyl-1,2-dioxetane (alkaline phosphatase substrate) XMD8-92 (extracellular signal-regulated kinase 5 inhibitor)-codelivered copper-tetrahydroxybenzoquinone (Cu-THBQ/AX) nanosized metal–organic framework in situ-generate therapeutic vaccination. Once inside early endosome, alkaline overexpressed cells' membrane activates situ type I photodynamic effect of Cu-THBQ/AX for generating •O2–, catalyzes O2 H2O2 •O2– •OH via semiquinone radical catalysis Fenton-like reactions. This surge ROS endosomes triggers caspase-3-mediated proinflammatory pyroptosis activating phospholipase C. Meanwhile, can also induce oligomerization dihydrolipoamide S-acetyltransferase trigger cell cuproptosis. The production could release effectively inhibiting efferocytosis macrophages convert apoptosis cells into secondary necrosis. simultaneous induction pyroptosis, cuproptosis, necrosis converts from "cold" "hot" conditions, making it antigen pool. transformation successfully antitumor response, growth metastasis.

Language: Английский

Citations

19
Electrochemical immunosensor utilizing Zn-Fe-N-C single-atom nanozyme and Ti3C2Tx@Au for ultrasensitive detection of cytokeratins21-1 DOI
Yingying Wang,

Fangqin Han,

Chunfang Cheng

et al.

Microchemical Journal, Journal Year: 2025, Volume and Issue: unknown, P. 112810 - 112810

Published: Jan. 1, 2025

Language: Английский

Citations

3
Application and progress of nanozymes in antitumor therapy DOI Creative Commons

Gaihua He,

Chao Mei,

Chenbo Chen

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 265, P. 130960 - 130960

Published: March 20, 2024

Tumors remain one of the major threats to public health and there is an urgent need design new pharmaceutical agents for their diagnosis treatment. In recent years, due rapid development nanotechnology, biotechnology, catalytic science, theoretical computing, subtlety has gradually made great progress in research related tumor Compared conventional drugs, enzymes can improve drug distribution enhance enrichment at site, thereby reducing side effects enhancing efficacy. Nanozymes also be used as tracking imaging reshape microenvironment, providing a versatile platform treatment malignancies. this paper, we review current status on oncology analyze novel therapeutic approaches mechanisms. To date, large number nanomaterials, such noble metal nonmetallic carbon-based have been shown able function like natural enzymes, particularly with significant advantages therapy. light this, authors systematically summarized evaluated construction, enzymatic activity, characteristics nanozymes respect modalities addition, application different types nicknames features years are detail. We conclude summary outlook study It hoped that will inspire researchers fields chemistry, biology, materials science contribute nano-enzymology.

Language: Английский

Citations

14
Cuproptosis in cancer: biological implications and therapeutic opportunities DOI Creative Commons
Liping Li,

Houfeng Zhou,

Chenliang Zhang

et al.

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: June 25, 2024

Abstract Cuproptosis, a newly identified copper (Cu)-dependent form of cell death, stands out due to its distinct mechanism that sets it apart from other known death pathways. The molecular underpinnings cuproptosis involve the binding Cu lipoylated enzymes in tricarboxylic acid cycle. This interaction triggers enzyme aggregation and proteotoxic stress, culminating death. specific has yet be fully elucidated. recognized sparked numerous investigations into role tumorigenesis cancer therapy. In this review, we summarized current knowledge on metabolism link cancer. Furthermore, delineated mechanisms roles cuproptosis-related genes Finally, offered comprehensive discussion most recent advancements ionophores nanoparticle delivery systems utilize as cutting-edge strategy for treatment.

Language: Английский

Citations

14
Nanomaterial-based regulation of redox metabolism for enhancing cancer therapy DOI

Xiaodan Jia,

Yue Wang, Yue Qiao

et al.

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

This review provides a comprehensive summary of the dysregulation redox metabolism in cancer cells and advantages latest advances nanomaterial-assisted metabolic regulation therapy.

Language: Английский

Citations

12
A Multifunctional Nanoreactor‐Induced Dual Inhibition of HSP70 Strategy for Enhancing Mild Photothermal/Chemodynamic Synergistic Tumor Therapy DOI

Shutong Wu,

Mengting Gao,

Lin Chen

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: May 9, 2024

Mild photothermal therapy (PTT) is a spatiotemporally controllable method that utilizes the effect at relatively low temperatures (40-45 °C) to especially eliminate tumor tissues with negligible side effects on surrounding normal tissues. However, overexpression of heat shock protein 70 (HSP70) and limited single treatment drastically impede therapeutic efficacy. Herein, constructed multifunctional core-shell structured Ag-Cu@SiO

Language: Английский

Citations

11