DNAzyme‐Mediated Cascade Nanoreactor for Cuproptosis‐Promoted Pancreatic Cancer Synergistic Therapy

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(28)

Published: Aug. 7, 2023

Abstract Cuproptosis, a kind of newly recognized cell death modality, shows enormous prospect in cancer treatment. The inducer cuproptosis has more advantages tumor therapy, especially that can trigger and chemodynamic therapy (CDT) simultaneously. However, is restricted to the deficiency intracellular copper ions nonspecific delivery copper‐based ionophores. Therefore, high level delivery, responsive release, utilizing synergistic‐function become key on cuproptosis‐based oncotherapy. In this work, cascade nanosystem constructed for enhanced CDT. weak acidic environment cells, DNA, zinc ions, Cu + release from nanosystem. Since having superior performance mediating both Fenton‐like reaction cuproptosis, released induces CDT efficiently, accompanied by 2+ generation. Then be converted into partially glutathione (GSH) supply loop ensure synergistic action. Meanwhile, consumption GSH also contributes return. Finally, DNA Zn form DNAzyme shear catalase‐related RNA, resulting accumulation hydrogen peroxide further enhancing combination therapy. These results provide promising nanotherapeutic platform may inspire design potential treatment based cuproptosis.

Language: Английский

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Biomaterials Elicit Pyroptosis Enhancing Cancer Immunotherapy

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 34(7)

Published: Nov. 5, 2023

Abstract Cancer immunotherapy has the potential to revolutionize treatment of malignant tumors, but its effectiveness is limited by low immune response rate and immune‐related adverse events. Pyroptosis, as an inflammatory programmed cell death type, triggers strong acute antitumor immunity, converting “cold” tumors “hot”. Particularly, biomaterials loading pyroptosis inducers targeting tumor microenvironment engineer pyroptosis, have achieved great progress in recent years. Herein, design strategy, mechanism pathway, role induce cancer are comprehensively reviewed. The present review focuses on application biomaterials‐induced immunotherapy, including nanogel, polymer prodrug, nanovesicle, mesoporous material. Additionally, synthesis a series stimuli‐responsive nanoplatforms, glutathione‐responsive, pH‐responsive, reactive oxygen species‐responsive, enzyme‐mimicking catalytic performance, described. Meanwhile, it augments multiple processes uptake, antigen presentation, T‐cell activation, expansion. Finally, perspectives pyroptosis‐mediated inflammation break through vascular basement membrane barrier achieving efficient volcanic penetration discussed. Artificial intelligence, multi‐omics analysis, anthropogenic animal models organoids presented, aiming provide guidance assistance for constructing effective controllable pyroptosis‐engineered improving immunotherapy.

Language: Английский

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Cuproptosis: Advances in Stimulus‐Responsive Nanomaterials for Cancer Therapy

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

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Activated aggregation‐induced emission therapeutics agents for triggering regulated cell death

Aggregate, Journal Year: 2024, Volume and Issue: 5(3)

Published: Jan. 22, 2024

Abstract The induction of regulated cell death (RCD) through photo/ultrasound sensitization therapeutic agents has gained significant attention as a vital approach to combat drug resistance in tumors. Aggregation‐induced emission (AIE) generate reactive oxygen species activation, which can synergize with RCD inducers or directly induce RCD, ultimately resulting the tumor cells. presented comprehensive review delves into recent advancements AIE designed trigger inducers, encompassing apoptosis, necroptosis, pyroptosis, immunogenic death, autophagy, ferroptosis, and cuproptosis. Additionally, intricate regulatory mechanisms activatory‐AIE therapeutics influence distinct pathways are examined. A forward‐looking perspective on future developments pertinent challenges within this exciting realm is presented, anticipating continued evolution activatable transformative enhance therapy.

Language: Английский

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“Multi‐in‐One” Yolk‐Shell Structured Nanoplatform Inducing Pyroptosis and Antitumor Immune Response Through Cascade Reactions

Small, Journal Year: 2024, Volume and Issue: 20(30)

Published: Feb. 25, 2024

Abstract Pyroptosis, a new mode of regulatory cell death, holds promising prospect in tumor therapy. The occurrence pyroptosis can trigger the release damage‐associated molecular patterns (DAMPs) and activate antitumor immune response. Moreover, enhancing intracellular reactive oxygen species (ROS) generation effectively induce pyroptosis. Herein, an integrated nanoplatform (hCZAG) based on zeolitic imidazolate framework‐8 (ZIF‐8) with Cu 2+ Zn as active nodes glucose oxidase (GOx) loading is constructed to evoke GOx elevate hydrogen peroxide (H 2 O ) levels regulate unfavorable microenvironment (TME). be reduced + by endogenous overexpressed GSH both exert Fenton‐like activity promote ROS amplify oxidative stress. In addition, accumulation leads aggregation lipoylated dihydrolipoamide S‐acetyltransferase (DLAT), thus resulting cuproptosis. Notably, outburst induced hCZAG activates Caspase‐1 proteins, cleavage gasdermin D (GSDMD), induces Pyroptosis further elicits adaptive response, leading immunogenic death (ICD). This study provides effective strategies for triggering pyroptosis‐mediated immunotherapy achieving improved therapeutic effects.

Language: Английский

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Tumor Metabolism Aiming Cu_2–xS Nanoagents Mediate Photothermal-Derived Cuproptosis and Immune Activation

ACS Nano, Journal Year: 2024, Volume and Issue: 18(35), P. 23941 - 23957

Published: Aug. 22, 2024

Cuproptosis is an emerging form of cell death that relies on the targeted delivery copper ions to lipoylated tricarboxylic acid cycle proteins. However, a major challenge associated with cuproptosis its potential kill both normal and tumor cells without discrimination. Therefore, it crucial develop strategies for precise intracellular redox control create effective cuproptosis-based therapies. We have introduced class nanoagents called metabolism aiming Cu

Language: Английский

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Biodegradable pyroptosis inducer with multienzyme-mimic activity kicks up reactive oxygen species storm for sensitizing immunotherapy

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 370, P. 438 - 452

Published: May 6, 2024

Language: Английский

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An ATP-responsive metal–organic framework against periodontitis via synergistic ion-interference-mediated pyroptosis

National Science Review, Journal Year: 2024, Volume and Issue: 11(8)

Published: June 26, 2024

ABSTRACT Periodontitis involves hyperactivated stromal cells that recruit immune cells, exacerbating inflammation. This study presents an ATP-responsive metal–organic framework (Mg/Zn-MOF) designed for periodontitis treatment, utilizing ion interference to modulate responses and prevent tissue destruction. Addressing the challenges of synergistic effects targeted delivery faced by traditional immunomodulatory nanomaterials, Mg/Zn-MOF system is activated extracellular ATP—a pivotal molecule in pathology—ensuring release. Magnesium zinc ions released from synergistically inhibit membrane pore formation attenuating Gasdermin D (GSDMD) expression activation. action curtails pyroptosis, lactate dehydrogenase IL-1β release, thwarting onset inflammatory cascades. Mechanistically, intervenes both NLRP3/Caspase-1/GSDMD Caspase-11/GSDMD pathways mitigate pyroptosis. In vivo assessments confirm its effectiveness diminishing cell infiltration preserving collagen integrity, thereby safeguarding against periodontal damage bone loss. investigation highlights promise ion-interference strategies immunotherapy, representing a significant stride developing therapeutic approaches.

Language: Английский

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Acid‐Responsive Nanoregulators Elicit Hydrogen Sulfide‐Mediated Tumor Oxygenation and Selective Sonosensitization for Hypoxic Tumors

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

Published: Jan. 19, 2025

Abstract Oxygen (O 2 ) tension within a tumor is considered hallmark of sonodynamic therapy (SDT). Herein, multifunctional nanoregulators, CMCS‐Au‐SrS (CAS), are reported, which assembled by carboxymethyl chitosan(CMCS) tethered gold nanoclusters (Au NCs) as sonosensitizers and sulfurate donors strontium sulfide nanoparticles (SrS NPs), to evoke selective SDT in hypoxic tumors. CAS possess tumor‐acidity responsiveness form large‐size aggregated Au NCs with shortened bandgap so that effectively induce powerful reactive oxygen species generation. On the other hand, acidity triggers degradation SrS NPs release hydrogen (H S), evoking oxygenation overcome hypoxia. This junction accelerated sonosensiting ability boosts amplified efficacy. More importantly, specific glycolysis induced acidification leads selectively accumulated cancer cells, further guaranteeing execution advanced therapeutic manners. Additionally, doping Nd 3+ endows second near‐infrared fluorescence facilitate vivo tracing property good tissue penetration (up 6 mm). strategy may play pioneering role develop theranostic reagents improved enrichment capacity enhanced hypoxia

Language: Английский

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The Role of Copper Ions in Mediating the Anti‐Cancer Effects Using Nanomaterials

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

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