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Nano Research https://doi.org/10.1007/s12274-024-6492-x
Research Article | Online first | Published: 27 February 2024

Multifunctional RGD coated a single-atom iron nanozyme: A highly selective approach to inducing ferroptosis and enhancing immunotherapy for pancreatic cancer

Show Author's Information Haoqi Pan1,2,3,4,§,  Xu Chen5,§,  Mingming Xiao1,2,  He Xu1,2,  Jiansheng Guo6,  Zhiyi Lu5,  Dong Cen7( ),  Xianjun Yu1,2( ),  Si Shi3,4( )
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
Key Laboratory of Advanced Fuel Cells and Electrolyzers Technology of Zhejiang Province, Qianwan Institute of CNITECH, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, China
Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China

§ Haoqi Pan and Xu Chen contributed equally to this work.

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immunotherapy, pancreatic cancer, ferroptosis, single-atom iron nanozyme
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Pan H, Chen X, Xiao M, et al. Multifunctional RGD coated a single-atom iron nanozyme: A highly selective approach to inducing ferroptosis and enhancing immunotherapy for pancreatic cancer. Nano Research, 2024, https://doi.org/10.1007/s12274-024-6492-x
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Abstract Full text Electronic supplementary material About this article

Nanozyme is a new promising approach to cancer therapy for its ability to induce ferroptosis by activating H2O2 via a traditional radical pathway and enhance cancer immunotherapy. However, short half-life period of hydroxyl radical (·OH) results in unsatisfied effectiveness. Herein, we synthesized a single-atom iron nanozyme (Fe-SAzyme), which can activate H2O2 via a non-radical pathway to generate Fe-based reactive oxygen species (ROS) (O=FeO3=O) for promoting the ferroptosis of pancreatic cancer cells. This Fe-SAzyme could be specifically phagocytosed by pancreatic cancer cells, increasing ROS levels and inhibiting glutathione (GSH) synthesis, which activates ferroptosis. Tumor magnetic resonance imaging (MRI) showed decreased T2 signal after intravenous injection of RGD@Fe-AC (AC = activated carbon). Moreover, RGD@Fe-AC promoted dendritic cell (DC) maturation, overcame Treg-mediated immunosuppression, activated T cells to trigger adaptive immune responses, and enhanced the efficacy of α-PD-L1 immunotherapy. Our research demonstrated that RGD@Fe-AC provided a straightforward, easily implemented, and selective approach for pancreatic cancer treatment and immunotherapy.


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Electronic supplementary material
About this article

Multifunctional RGD coated a single-atom iron nanozyme: A highly selective approach to inducing ferroptosis and enhancing immunotherapy for pancreatic cancer

Show Author's information Haoqi Pan1,2,3,4,§, Xu Chen5,§, Mingming Xiao1,2, He Xu1,2, Jiansheng Guo6, Zhiyi Lu5, Dong Cen7( ), Xianjun Yu1,2( ), Si Shi3,4( )
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Shanghai Pancreatic Cancer Institute, Shanghai 200032, China
Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
Key Laboratory of Advanced Fuel Cells and Electrolyzers Technology of Zhejiang Province, Qianwan Institute of CNITECH, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, China
Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China

§ Haoqi Pan and Xu Chen contributed equally to this work.

Abstract

Nanozyme is a new promising approach to cancer therapy for its ability to induce ferroptosis by activating H2O2 via a traditional radical pathway and enhance cancer immunotherapy. However, short half-life period of hydroxyl radical (·OH) results in unsatisfied effectiveness. Herein, we synthesized a single-atom iron nanozyme (Fe-SAzyme), which can activate H2O2 via a non-radical pathway to generate Fe-based reactive oxygen species (ROS) (O=FeO3=O) for promoting the ferroptosis of pancreatic cancer cells. This Fe-SAzyme could be specifically phagocytosed by pancreatic cancer cells, increasing ROS levels and inhibiting glutathione (GSH) synthesis, which activates ferroptosis. Tumor magnetic resonance imaging (MRI) showed decreased T2 signal after intravenous injection of RGD@Fe-AC (AC = activated carbon). Moreover, RGD@Fe-AC promoted dendritic cell (DC) maturation, overcame Treg-mediated immunosuppression, activated T cells to trigger adaptive immune responses, and enhanced the efficacy of α-PD-L1 immunotherapy. Our research demonstrated that RGD@Fe-AC provided a straightforward, easily implemented, and selective approach for pancreatic cancer treatment and immunotherapy.

Keywords: immunotherapy, pancreatic cancer, ferroptosis, single-atom iron nanozyme

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Publication history
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Acknowledgements

Publication history

Received: 28 November 2023
Revised: 10 January 2024
Accepted: 15 January 2024
Published: 27 February 2024

Copyright

© Tsinghua University Press 2024

Acknowledgements

Acknowledgements

The authors acknowledge the support from the National Natural Science Foundation of China (Nos. U21A20374, 82102903, and 52201285), Natural Science Foundation of Shanghai (No. 23ZR1479300), Shanghai Municipal Science and Technology Major Project (No. 21JC1401500), Scientific Innovation Project of Shanghai Education Committee (No. 2019-01-07-00-07-E00057), Zhejiang Provincial Natural Science Foundation (No. LQ22H160005), Zhejiang Medical Health Science and Technology Program (No. 2023RC031), and Ningbo Yongjiang Talent Introduction Program (No. 2021A-036-B).

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