Stimulus‐Responsive Copper Complex Nanoparticles Induce Cuproptosis for Augmented Cancer Immunotherapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)

Published: Jan. 25, 2024

Abstract Cuproptosis, an emerging form of programmed cell death, has received tremendous attention in cancer therapy. However, the efficacy cuproptosis remains limited by poor delivery efficiency copper ion carriers. Herein, complex nanoparticles (denoted as Cu(I) NP) are developed that can efficiently deliver into cells to induce cuproptosis. NP demonstrate stimulus‐responsive release complexes, which results mitochondrial dysfunction and promotes aggregation lipoylated dihydrolipoamide S‐acetyltransferase (DLAT), leading Notably, not only cuproptosis, but also elicit robust immune responses suppress tumor growth. Overall, this study provides a promising strategy for cuproptosis‐based

Language: Английский

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Bioactive Layered Double Hydroxides for Synergistic Sonodynamic/Cuproptosis Anticancer Therapy with Elicitation of the Immune Response

ACS Nano, Journal Year: 2024, Volume and Issue: 18(15), P. 10495 - 10508

Published: April 1, 2024

Sonodynamic therapy (SDT) has promising application prospects in tumor therapy. However, SDT does not eradicate metastatic tumors. Herein, Cu-substituted ZnAl ternary layered double hydroxide nanosheets (ZCA NSs) were developed as both sonosensitizers and copper nanocarriers for synergistic SDT/cuproptosis cancer An optimized electronic structure more conducive to the sonodynamic process was obtained from ZCA NSs via Jahn–Teller effect induced by introduction of Cu2+, synthesized regulated intricate microenvironment (TME) depleting endogenous glutathione (GSH) amplify oxidative stress further enhanced performance. Furthermore, cuproptosis evoked intracellular overload Cu2+ amplified SDT, leading irreversible proteotoxicity. In vitro results showed that such synergetic triggered immunogenic cell death (ICD) promoted maturation dendritic cells (DCs). as-synthesized NS-mediated thoroughly eradicated vivo solid tumors simultaneously elicited antitumor immunity suppress lung liver metastasis. Overall, this work established a nanoplatform with satisfactory immunity.

Language: Английский

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A Vacancy‐Engineering Ferroelectric Nanomedicine for Cuproptosis/Apoptosis Co‐Activated Immunotherapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(30)

Published: May 4, 2024

Abstract Low efficacy of immunotherapy due to the poor immunogenicity most tumors and their insufficient infiltration by immune cells highlights importance inducing immunogenic cell death activating system for achieving better treatment outcomes. Herein, ferroelectric Bi 2 CuO 4 nanoparticles with rich copper vacancies (named BCO‐V Cu ) are rationally designed engineered ferroelectricity‐enhanced apoptosis, cuproptosis, subsequently evoked immunotherapy. In this structure, suppressed recombination electron–hole pairs band bending polarization lead high catalytic activity, triggering reactive oxygen species bursts apoptosis. The fragments produced apoptosis serve as antigens activate T cells. Moreover, generated charge catalysis, nanomedicine can act “a smart switch” open membrane, promote nanomaterial endocytosis, shut down + outflow pathway evoke thus a strong response is triggered reduced content adenosine triphosphate. Ribonucleic acid transcription tests reveal pathways related activation. Thus, study firstly demonstrates feasible strategy enhancing using single semiconductor‐induced cuproptosis.

Language: Английский

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Enzyme Core Spherical Nucleic Acid That Enables Enhanced Cuproptosis and Antitumor Immune Response through Alleviating Tumor Hypoxia

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

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Biomimetic copper-doped polypyrrole nanoparticles induce glutamine metabolism inhibition to enhance breast cancer cuproptosis and immunotherapy

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

Published: May 31, 2024

Language: Английский

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Cuproptosis: unveiling a new frontier in cancer biology and therapeutics

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

Published: May 1, 2024

Copper plays vital roles in numerous cellular processes and its imbalance can lead to oxidative stress dysfunction. Recent research has unveiled a unique form of copper-induced cell death, termed cuproptosis, which differs from known death mechanisms. This process involves the interaction copper with lipoylated tricarboxylic acid cycle enzymes, causing protein aggregation death. Recently, growing number studies have explored link between cuproptosis cancer development. review comprehensively examines systemic metabolism copper, including tumor-related signaling pathways influenced by copper. It delves into discovery mechanisms connection various cancers. Additionally, suggests potential treatments using ionophores that induce combination small molecule drugs, for precision therapy specific types.

Language: Английский

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Biometallic ions and derivatives: a new direction for cancer immunotherapy

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 15, 2025

Biometallic ions play a crucial role in regulating the immune system. In recent years, cancer immunotherapy has become breakthrough treatment, achieving good efficacy wide range of cancers with its specificity and durability advantages. However, existing therapies still face challenges, such as tolerance escape. (e.g. zinc, copper, magnesium, manganese, etc.) can assist enhancing through activation cells, enhancement tumor antigen presentation, improvement microenvironment. addition, biometallic derivatives directly inhibit cell progression offer possibility effectively overcoming limitations current by promoting responses reducing immunosuppressive signals. This review explores potential application prospects immunotherapy, providing new ideas for future clinical metal part helping to guide development more effective safe therapeutic regimens.

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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Redox-manipulating nanocarriers for anticancer drug delivery: a systematic review

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 28, 2024

Language: Английский

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Synthesis of Fe3O4@SiO2-creatine as a new nanosorbent for dispersive magnetic solid-phase microextraction of copper ions from water, food, and soil samples

Journal of Food Composition and Analysis, Journal Year: 2024, Volume and Issue: 129, P. 106097 - 106097

Published: Feb. 23, 2024

Language: Английский

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