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A Synergistic Dual-Atom Sites Nanozyme Augments Immunogenic Cell Death for Efficient Immunotherapy.

作者信息

Ning Shipeng, Zhang Zeyuan, Ren Yujing, Hou Yaxin, Li Dan, Chen Jingqi, Zhai Yujie, Fan Kelong, Zhang Weiqing

机构信息

Department of Breast Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530000, China.

Department of Research, Guangxi Medical University Cancer Hospital, Guangxi Medical University, Nanning, 530021, China.

出版信息

Adv Sci (Weinh). 2025 Feb;12(7):e2414734. doi: 10.1002/advs.202414734. Epub 2024 Dec 24.


DOI:10.1002/advs.202414734
PMID:39716966
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11831451/
Abstract

Inducing immunogenic cell death (ICD) is a promising approach to elicit enduring antitumor immune responses. Hence, extensive efforts are being made to develop ICD inducers. Herein, a cascaded dual-atom nanozyme with Fe and Cu sites (FeCu-DA) as an efficient ICD inducer is presented. The Fe and Cu dual-atom sites synergistically enhance peroxidase (POD) and catalase activities, effectively converting intratumoral hydrogen peroxide (HO) to hydroxyl radicals (·OH) and oxygen (O). Moreover, FeCu-DA exhibits superior glutathione-oxidase (GSH-OXD) activity, catalyzing GSH oxidation to generate HO, enabling cascaded catalysis for sustainable ∙OH generation and reducing reactive oxygen species (ROS) resistance by consuming GSH. Steady-state kinetic analysis and density functional theory calculations indicate that FeCu-DA exhibits a higher catalytic rate and efficiency than Fe single-atom nanozymes (Fe-SA) because of its stronger interactions with HO. Its POD activity is 948.05 U mg, which is 2.8-fold greater than that of Fe-SA. Furthermore, FeCu-DA exhibits impressive photothermal effects and photothermal-enhanced cascaded catalysis kinetics for ROS generation, thereby inducing potent ICD. Combined with anti-PD-L1 antibody (αPD-L1) blockade, FeCu-DA shows synergistic enhancement in treatment under near-infrared irradiation. This study provides insights for designing efficient dual-atom nanozymes and demonstrates their potential in ICD-induced cancer immunotherapy.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/d92fb5fcf477/ADVS-12-2414734-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/0a37123a3452/ADVS-12-2414734-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/546356f76e89/ADVS-12-2414734-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/292e4ca2edef/ADVS-12-2414734-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/415f30336417/ADVS-12-2414734-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/7fba961fb9fb/ADVS-12-2414734-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/0f75683e6d6c/ADVS-12-2414734-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/0bb4ac1cf838/ADVS-12-2414734-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/d92fb5fcf477/ADVS-12-2414734-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/0a37123a3452/ADVS-12-2414734-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/546356f76e89/ADVS-12-2414734-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/292e4ca2edef/ADVS-12-2414734-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/415f30336417/ADVS-12-2414734-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/7fba961fb9fb/ADVS-12-2414734-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/0f75683e6d6c/ADVS-12-2414734-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/0bb4ac1cf838/ADVS-12-2414734-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1424/11831451/d92fb5fcf477/ADVS-12-2414734-g004.jpg

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引用本文的文献

[1]
Reprogramming the tumor-immune landscape via nanomaterial-induced immunogenic cell death: a mini review.

Front Bioeng Biotechnol. 2025-7-22

[2]
Mechanism and application of copper-based nanomedicines in activating tumor immunity through oxidative stress modulation.

Front Pharmacol. 2025-7-11

本文引用的文献

[1]
Synergistic Al-Al Dual-Atomic Site for Efficient Artificial Nitrogen Fixation.

Angew Chem Int Ed Engl. 2024-6-10

[2]
Precise Tuning of the D-Band Center of Dual-Atomic Enzymes for Catalytic Therapy.

J Am Chem Soc. 2024-4-10

[3]
Regulation and impact of tumor-specific CD4 T cells in cancer and immunotherapy.

Trends Immunol. 2024-4

[4]
A Single-Atom Manganese Nanozyme Mn-N/C Promotes Anti-Tumor Immune Response via Eliciting Type I Interferon Signaling.

Adv Sci (Weinh). 2024-4

[5]
Engineering Atomically Dispersed Cu-NS Sites via Chemical Vapor Deposition to Boost Enzyme-Like Activity for Efficient Tumor Therapy.

Adv Mater. 2024-3

[6]
Interfacial strong interaction-enabling cascade nanozymes for apoptosis-ferroptosis synergistic therapy.

J Colloid Interface Sci. 2024-1

[7]
Janus Silica Nanoparticle-Based Tumor Microenvironment Modulator for Restoring Tumor Sensitivity to Programmed Cell Death Ligand 1 Immune Checkpoint Blockade Therapy.

ACS Nano. 2023-8-8

[8]
Atomic Insights into Synergistic Nitroarene Hydrogenation over Nanodiamond-Supported Pt -Fe Dual-Single-Atom Catalyst.

Angew Chem Int Ed Engl. 2023-9-4

[9]
Atomically Site Synergistic Effects of Dual-Atom Nanozyme Enhances Peroxidase-like Properties.

Nano Lett. 2023-7-12

[10]
Atomic-Level Regulation of Cobalt Single-Atom Nanozymes: Engineering High-Efficiency Catalase Mimics.

Angew Chem Int Ed Engl. 2023-5-2

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