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.
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).
作者简介
Haoqi Pan and Xu Chen contributed equally to this work;Address correspondence to Dong Cen,dongcen@zju.edu.cn;Address correspondence to Xianjun Yu,yuxianjun@fudanpci.org;Address correspondence to Si Shi,shisi@fudanpci.org。
