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

作　　者：Haoqi Pan Xu Chen Mingming Xiao He Xu Jiansheng Guo Zhiyi Lu Dong Cen Xianjun Yu Si Shi 

机构地区：[1]Department of Pancreatic Surgery,Fudan University Shanghai Cancer Center,Shanghai 200032,China [2]Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China [3]Shanghai Pancreatic Cancer Institute,Shanghai 200032,China [4]Pancreatic Cancer Institute,Fudan University,Shanghai 200032,China [5]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 [6]Department of Pathology of Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310016,China [7]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

出　　处：《Nano Research》2024年第6期5469-5478,共10页纳米研究（英文版）

基　　金：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);Ningbo Yongjiang Talent Introduction Program(No.2021A-036-B).

摘　　要：Nanozyme is a new promising approach to cancer therapy for its ability to induce ferroptosis by activating H_(2)O_(2)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 H_(2)O_(2)via a non-radical pathway to generate Fe-based reactive oxygen species(ROS)(O=FeO_(3)=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 ofα-PD-L1 immunotherapy.Our research demonstrated that RGD@Fe-AC provided a straightforward,easily implemented,and selective approach for pancreatic cancer treatment and immunotherapy.

关 键 词：single-atom iron nanozyme pancreatic cancer IMMUNOTHERAPY ferroptosis 

分 类 号：R730.51[医药卫生—肿瘤]