High Immunogenic Cuproptosis Evoked by In Situ Sulfidation‐Activated Pyroptosis for Tumor‐Targeted Immunotherapy of Colorectal Cancer DOI Creative Commons

Wentao Xiao,

Kuiming Qu,

Wei Zhang

et al.

Small Science, Journal Year: 2024, Volume and Issue: 4(3)

Published: Jan. 17, 2024

Despite the great potential of cuproptosis in tumor therapy, current cuproptosis‐based therapy still suffers from compromised efficiency immune activation. Pyroptosis, a proinflammatory cell death modality, provides good opportunity to induce immunogenic (ICD) and promote systemic response. However, synergistic pyroptosis has not been fully explored. Herein, it is discovered that Cu(II)‐based metal–organic framework (MOF) nanoparticles (NPs) can synergistically evoke ICD for high‐efficiency tumor‐targeted immunotherapy. Although MOF‐199 widely used immunogenicity unclear. Pluronic F127‐modified NPs ( F127 NPs) show dual‐responsiveness glutathione (GSH) hydrogen sulfide (H 2 S). Once entering cancer cells, dissociate GSH‐enriched microenvironment (TME) release copper ion copper‐overload‐mediated cuproptosis. Meanwhile, transform Cu 2− x S by situ sulfidation under H S‐enriched colorectal (CRC) TME. Under photothermal chemodynamic (PTT/CDT) NPs, caspase‐3 activated gasdermin E (GSDME)‐related triggered. The have proved superior antitumor immunity effect both vitro vivo experiments. This work new strategy achieve immunotherapy with high simple NPs.

Language: Английский

Enzyme Core Spherical Nucleic Acid That Enables Enhanced Cuproptosis and Antitumor Immune Response through Alleviating Tumor Hypoxia DOI
Yuting Huang, Xueliang Liu, Jiawei Zhu

et al.

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

Citations

36
Self‐Reinforced Bimetallic Mito‐Jammer for Ca2+ Overload‐Mediated Cascade Mitochondrial Damage for Cancer Cuproptosis Sensitization DOI Creative Commons

Chier Du,

Xun Guo,

Xiaoling Qiu

et al.

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

Citations

33
Design of Near Infrared Light‐Powered Copper Phyllosilicate Nanomotors for Cuproptosis‐Based Synergistic Cancer Therapy DOI

Yibo Song,

Guowu Zhan, Shu‐Feng Zhou

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(18)

Published: Jan. 23, 2024

Abstract Cuproptosis, a newly discovered cell death pathway, has shown great potential in cancer treatment. Herein, near‐infrared (NIR) light‐driven nanomotors (CuSiO 3 @Au‐Pd NMs) are designed for cuproptosis‐assisted synergistic therapy with autonomous mobility and improved cellular uptake tumor penetration. Specifically, the released Cu 2+ ions from CuSiO NMs can induce Fenton‐like reaction, leading to generation of hydroxyl radicals (·OH), accompanied by depletion glutathione within MCF‐7 cells. Additionally, also exhibit excellent photothermal effects, which further promote production ·OH, resulting intensified oxidative stress apoptosis. Moreover, enhanced permeation efficiency via movement under self‐thermophoretic forces proved using 2D experiments 3D multicellular spheroids. The resultant intracellular accumulation oligomerization lipoylated proteins, cuproptosis, along mitochondrial dysfunction pathway. More importantly, both vitro vivo show that could penetrate deeply into tumors anticancer efficacy through multimodal therapeutic methods. These findings manifest promising potentials NIR‐powered Cu‐based high maneuverability future smart therapy.

Language: Английский

Citations

29
Microfluidic Synthesis of CuH Nanoparticles for Antitumor Therapy through Hydrogen-Enhanced Apoptosis and Cuproptosis DOI

Guanzhong He,

Yongchun Pan,

Fei Zeng

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(12), P. 9031 - 9042

Published: March 12, 2024

Cuproptosis has drawn enormous attention in antitumor material fields; however, the responsive activation of cuproptosis against tumors using nanomaterials with high atom utilization is still challenging. Herein, a copper-based nanoplatform consisting acid-degradable copper hydride (CuH) nanoparticles was developed via microfluidic synthesis. After coating tumor-targeting hyaluronic acid (HA), denoted as HA-CuH-PVP (HCP) shows conspicuous damage toward tumor cells by generating Cu+ and hydrogen (H2) simultaneously. can induce apoptosis relying on Fenton-like reactions lead to causing mitochondrial protein aggregation. Besides, existence H2 enhance both cell death types dysfunction intracellular redox homeostatic disorders. In vivo experimental results further exhibit desirable potential HCP for killing inhibiting lung metastases, which will broaden horizons designing materials triggering better efficacy.

Language: Английский

Citations

29
A Copper/Ferrous‐Engineering Redox Homeostasis Disruptor for Cuproptosis/Ferroptosis Co‐Activated Nanocatalytic Therapy in Liver Cancer DOI
Xiaoling Zhang, Jiuxin Zhu,

Sihao Wang

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(37)

Published: April 25, 2024

Abstract Cuproptosis and ferroptosis hold great promise for overcoming apoptotic resistance in liver cancer based on their unique metal‐driven cell death modalities. However, insufficient intracellular copper iron concentration, complicated tumor microenvironment (TME), unclear cross‐regulatory mechanisms between cuproptosis ferroptosis, severely restrict the therapeutic performance. Herein, copper‐doped hollow Prussian blue (CHP) nanozymes are rationally designed loading photosensitizer indocyanine green (ICG) O 2 ‐saturated perfluorohexane (PFH), denoted as ‐PFH@CHPI nanoparticles, to induce ferroptosis. In response specific TME, CHP can synergistically catalyze Fenton reactions consume endogenous glutathione, leading accumulation of reactive oxygen species. Upon near‐infrared irradiation, ‐PFH@CHPI‐enabled photothermal effect simultaneously accelerate catalytic trigger release photodynamic therapy promote oxidative stress. Notably, be effectively activated through Cu + ‐mediated dihydrolipoamide S‐acetyltransferase aggregation Fe–S cluster protein loss. Concurrently, tilt redox balance is favorable lipid peroxidation glutathione peroxidase 4 inactivation, resulting an augmented effect. Mechanistically, stress‐boosted jointly disrupt mitochondrial metabolism, which turn exacerbates stress, thus realizing a mutually enhanced This work may provide new guidance utilizing copper/ferrous‐engineering cuproptosis/ferroptosis synergetic therapy.

Language: Английский

Citations

29
In situ hydrogel based on Cu–Fe3O4 nanoclusters exploits oxidative stress and the ferroptosis/cuproptosis pathway for chemodynamic therapy DOI
Yiqun Zhang, Ni Zhang,

Jianghao Xing

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 311, P. 122675 - 122675

Published: June 26, 2024

Language: Английский

Citations

29
A cuproptosis nanocapsule for cancer radiotherapy DOI
You Liao, Dongmei Wang,

Chenglu Gu

et al.

Nature Nanotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 19, 2024

Language: Английский

Citations

23
An Intelligent Cupreous Nanoplatform with Self-Supplied H2O2 and Cu2+/Cu+ Conversion to Boost Cuproptosis and Chemodynamic Combined Therapy DOI

Xiangjie Tian,

Hui Xu, Fangfang Zhou

et al.

Chemistry of Materials, Journal Year: 2024, Volume and Issue: 36(2), P. 815 - 828

Published: Jan. 11, 2024

Cuproptosis is a newly identified copper-dependent cell death and holds great promise for cancer therapy. However, transporting enough copper into cells challenge. Herein, an intelligent cupreous nanoplatform (denoted as CuO2-MSN@TA-Cu2+), consisting of in situ formation CuO2 within mesoporous silica nanoparticles (MSN) then deposition with tannic acid (TA)-Cu2+ complex, designed developed to realize on-demand delivery cuproptosis-based combination CuO2-MSN@TA-Cu2+ exhibits tumor microenvironment-triggered therapeutic activity, wherein the outer TA-Cu2+ complex readily disassembled release Cu2+ liberate internal produce H2O2. The overloaded can not only directly convert endogenous H2O2 self-supplied highly toxic hydroxyl radicals chemodynamic therapy (CDT) via Cu-based Fenton-like reaction but also undergo glutathione-mediated reduction Cu+ species induce potent cellular cuproptosis enhance CDT. experimental results indicate that produces remarkable cytotoxicity against significantly suppresses growth by 93.42% mice-bearing 4T1 breast tumors. This work provides new paradigm boost cuproptosis-related may inspire design advanced nanoplatforms.

Language: Английский

Citations

20
Mitochondrial‐Targeted Copper Delivery for Cuproptosis‐Based Synergistic Cancer Therapy DOI

Jinpeng Deng,

Huilan Zhuang,

Sijie Shao

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(18)

Published: March 26, 2024

Cuproptosis is dependent on mitochondrial respiration modulation by targeting lipoylated tricarboxylic acid cycle (TCA) proteins, showing great potential in cancer treatment. However, the specific release of copper ions at highly needed and still a major challenge to trigger cellular cuproptosis. Herein, metal-organic framework-based nanoplatform (ZCProP) designed for mitochondrial-targeted ATP/pH-responsive Cu

Language: Английский

Citations

20
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

20