Jing Kong,1,* Jiabin Lai,2– 4,* Min Wang,5,* Yi Xie,1 Haifei He,6 Jiayu Gu,7 Tao Pan,6 Zhiqiang Lu,8 Lifeng Jiang3,4 

1Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedic Research Institute of Zhejiang University, Hangzhou, People’s Republic of China; 4Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, People’s Republic of China; 5Digestive Endoscopy Department, The First Affiliated Hospital with Nanjing Medical University & Jiangsu Province Hospital, Nanjing, People’s Republic of China; 6Department of Breast Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 7Jiangsu Institute of Metrology, Nanjing, People’s Republic of China; 8Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Lifeng Jiang; Zhiqiang Lu, Email jianglifeng@zju.edu.cn; taiyi1981@126.com

Background: Chemodynamic therapy (CDT) faces challenges of low catalytic ion efficiency and ROS production. We developed a ROS nano-bomb, Cu/ZIF-8@GA-Fe, to address these issues.
Methods: The nano-bomb was synthesized by doping copper into ZIF-8 and assembling Fe3+ and gallic acid (GA). It was tested for reactive oxygen species (ROS) generation in acidic conditions and its photothermal properties.
Results: In an acidic micro environment, Cu/ZIF-8@GA-Fe effectively released Fe3+ and Cu2+, depleting GSH and generating ROS. The GA-Fe coating provided photothermal heat and was used to enhance Fenton reactions via dual ions for increasing ROS production. In vivo and in vitro experiments, Cu/ZIF-8@GA-Fe inhibited tumor growth with minimal side effects.
Conclusion: Cu/ZIF-8@GA-Fe shows promise for safe and effective CDT, offering a synergistic approach to tumor therapy.

Keywords: reactive oxygen species, nano-bomb, combination therapy, chemodynamic therapy, photothermal therapy