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

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

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Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives

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

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Advances in cuproptosis harnessing copper-based nanomaterials for cancer therapy

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

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Dual‐Release Free Iron and Breakdown of Ferroptosis Defenses to Achieve Ferroptosis Cascade Storms for Potent Antitumor Therapy

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

Abstract Ferroptosis is a newly identified type of regulated cell death characterized by iron‐dependent lipid peroxidation. Among the main ferroptosis‐suppressing systems, dihydroorotate dehydrogenase (DHODH)‐ ubiquinone axis closely related to mitochondria and energy metabolism, implying that protects cells from oxidative stress damage via maintenance redox homeostasis. However, ferroptosis initiation requires suitable environment breakthrough in homeostatic limitations systems. Hence, nanoparticles are rationally engineered achieve efficient induction releasing dual‐release free iron disrupting Atovaquone (ATO)‐loaded hollow mesoporous etching zeolitic imidazolate framework‐67 double‐coated oxide/calcium phosphate (Fe 3 O 4 /CaP) conjugated with polyethylene glycol. The external Fe /CaP structure enhances efficiency multiple reactive oxygen species (ROS) generation promoting stress. Still, it achieves increase content unstable pools for igniting ROS storm peroxidation spark. release ATO not only affects metabolism mitochondrial respiratory chain binding complex III but also downregulates DHODH restrict ubiquinol system disrupt Therefore, design this composite nanomedicine provides an approach inducing theoretical basis clinical anti‐tumor trials.

Language: Английский

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Tumor Microenvironment‐Driven Structural Transformation of Vanadium‐Based MXenzymes to Amplify Oxidative Stress for Multimodal Tumor Therapy

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

Published: Jan. 23, 2025

MXenzymes, a promising class of catalytic therapeutic material, offer great potential for tumor treatment, but they encounter significant obstacles due to suboptimal efficiency and kinetics in the microenvironment (TME). Herein, this study draws inspiration from electronic structure transition metal vanadium, proposing leverage TME specific-features induce structural transformations sheet-like vanadium carbide MXenzymes (TVMz). These trigger cascading reactions that amplify oxidative stress, thereby significantly enhancing multimodal therapy. Specifically, engineered HTVMz, coated with hyaluronic acid, exhibits good stability generates thermal effect under NIR-II laser irradiation. The effect, combined characteristics, facilities transformation into ultra-small oxide nanozymes (VOx). enlarged surface area VOx substantially enhances ROS regeneration amplifies which promotes lysosomal permeability induces endoplasmic reticulum stress. high-valent interacts intracellular glutathione, disrupting redox homeostasis intensifying stress further. amplifications accelerate apoptosis, ferroptosis, suppress HSP90 expression. Consequently, heightened sensitivity HTVMz synergistically cell death via pathways. This presents an innovative strategy therapy by manipulating structures, advancing field

Language: Английский

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Bioactive metal-based nanomedicines for boosting anti-tumor immunity: Advance, challenge, and perspective

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 517, P. 215969 - 215969

Published: June 10, 2024

Language: 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, 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

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Targeting the initiator to activate both ferroptosis and cuproptosis for breast cancer treatment: progress and possibility for clinical application

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 10, 2025

Breast cancer is the most commonly diagnosed worldwide. Metal metabolism pivotal for regulating cell fate and drug sensitivity in breast cancer. Iron copper are essential metal ions critical maintaining cellular function. The accumulation of iron triggers distinct death pathways, known as ferroptosis cuproptosis, respectively. Ferroptosis characterized by iron-dependent lipid peroxidation, while cuproptosis involves copper-induced oxidative stress. They increasingly recognized promising targets development anticancer drugs. Recently, compelling evidence demonstrated that interplay between plays a crucial role progression. This review elucidates converging pathways Moreover, we examined value genes associated with clinical diagnosis treatment cancer, mainly outlining potential co-targeting approach. Lastly, delve into current challenges limitations this strategy. In general, offers an overview interaction offering valuable perspectives further research treatment.

Language: Английский

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Enhancing Photodynamic Therapy Efficacy via Photo-Triggered Calcium Overload and Oxygen Delivery in Tumor Hypoxia Management

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Background: Photodynamic therapy (PDT) has emerged as a promising treatment for cancer, primarily due to its ability generate reactive oxygen species (ROS) that directly induce tumor cell death. However, the hypoxic microenvironment commonly found within tumors poses significant challenge by inhibiting ROS production. This study aims investigate effect of improving hypoxia on enhancing PDT. Result: We employed polylactic-co-glycolic acid (PLGA) delivery vector encapsulation indocyanine green (ICG), photosensitizer, and perfluorohexane (PFH), with surface labeling mannose facilitate targeted delivery. A potential therapeutic nanoplatform was fabricated, designated Man-PFH-ICG@PLGA. These nanospheres are capable localizing at sites can be tracked using photoacoustic (PA) imaging. Upon laser irradiation, generated PDT activated transient receptor cation channel subfamily member 1 (TRPA1) located membrane. activation led an influx extracellular Ca2+ subsequently resulted in calcium overload. The excessive selectively accumulated mitochondria, disrupting function enzymes involved mitochondrial respiratory chain. disruption inhibits cellular respiration decreases consumption cells, ultimately contributing alleviation tumors. Simultaneously, PFH exhibited high affinity deliver exogenous site through simple diffusion along concentration gradient. Both direct indirect mechanisms synergistically contribute ameliorating conditions tumors, thereby augmenting efficacy Conclusions: synergistic photocontrolled overload from endogenous sources oxygen-carrying alleviates hypoxia, approach provides new perspective

Language: Английский

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H₂O₂‐Generating Advanced Nanomaterials for Cancer Treatment

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Abstract Tumor cells exploit abnormal redox homeostasis and the pro‐tumorigenic effect of reactive oxygen species (ROS) to enhance their survival progression. However, excessively high levels ROS can exceed oxidative stress threshold tumor cells, inducing cell death. This occur by selectively elevating concentration H 2 O in through both endogenous exogenous mechanisms. The generated serves as a precursor for toxic ROS, such • OH 1 , via chemodynamic photodynamic therapy, respectively, leading apoptosis, necrosis, ferroptosis. Strategies boost include direct delivery amplifying generation inhibiting antioxidant enzymes, leveraging glucose oxidase, employing photocatalytic therapy (PCT), utilizing metal peroxides. Among them, peroxides have displayed remarkable performance due excellent potential elevate within while simultaneously normalizing acidic hypoxic conditions microenvironment (TME). Moreover, these nanostructures sensitivity complementary treatments, like chemotherapy. review summarizes advanced perspectives design, synthesis, comparative analysis ‐generating nanoplatforms, emphasizing capacity treat various cancers.

Language: Английский

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