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Vol. 18 (2026)

Copper-Based Targeted Nanocatalytic Therapeutics for Non-Small Cell Lung Cancer

https://doi.org/10.1007/s40820-025-01998-5
Yongfei Fan
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, People’s Republic of China
Jiao Chang
Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200331, People’s Republic of China
Xichun Qin
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, People’s Republic of China
Meng Li
Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200331, People’s Republic of China
Yan Li
Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200331, People’s Republic of China
Leilei Wu
Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, People’s Republic of China
Kun Li
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, People’s Republic of China
Zhimin Chen
Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, People’s Republic of China
Yani Li
Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200331, People’s Republic of China
Zhongmin Tang
Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200331, People’s Republic of China
Dong Xie
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, People’s Republic of China
Jianlin Shi
Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai 200050, People’s Republic of China

Corresponding Author: Dong Xie

xiedong@tongji.edu.cn

Nano-Micro Letters, Vol. 18 (2026), Article Number: 152

Abstract

Conventional treatments for non-small cell lung cancer (NSCLC) suffer from low remission rates, high drug resistance, and severe adverse effects. To leverage the therapeutic potential of reactive oxygen species (ROS), nanocatalytic medicine utilizes nanomaterials to generate ROS specifically within tumor sites, enabling efficient and targeted cancer treatment. In this study, hyaluronic acid (HA)-modified copper-N,N-dimethyl-N-phenylsulfonylbisamine (DMSA)-assembled nanoparticles (Cu-DMSA-HA NPs) are developed with tumor-targeting capability and efficiently catalyze ROS production via coordination chemistry. Targeted delivery is facilitated by HA surface modification through recognition of overexpressed cluster of differentiation 44 receptors on cancer cells, which enhances nanoparticle uptake. Once internalized, intracellular glutathione is depleted by the NPs, followed by a Fenton-like reaction that sustains ROS production. Both in vitro and in vivo studies demonstrate that this catalytic strategy effectively inhibits DNA replication, prevents cell cycle progression, downregulates glutathione peroxidase 4 expression, induces ferroptosis, and ultimately suppresses NSCLC progression. Overall, the readily prepared Cu-DMSA-HA NPs exhibit robust catalytic activity and tumor specificity, highlighting their strong potential for clinical translation in nanocatalytic cancer therapy.


Highlights:
1 Developed a novel type of nanoparticles (NPs)—hyaluronic acid (HA)-modified copper-N,N-dimethyl-N-phenylsulfonylbisamine (DMSA)-assembled NPs (Cu-DMSA-HA NPs).
2 The constructed NPs were surface-modified with HA to selectively target overexpressed cluster of differentiation 44 (CD44) receptors on cancer cells and catalytically generate highly efficient reactive oxygen species (ROS) via coordination chemistry.
3 Such efficient ROS generation induced intracellular ROS accumulation, mitochondrial disruption, glutathione (GSH) depletion, and glutathione peroxidase 4 (GPX4) downregulation, ultimately triggering ferroptosis in cancer cells.

Keywords

Nanocatalytic medicine Reactive oxygen species Lung cancer therapy Copper-based nanoparticles
Fan, Yongfei, Jiao Chang, Xichun Qin, Meng Li, Yan Li, Leilei Wu, Kun Li, Zhimin Chen, Yani Li, Zhongmin Tang, Dong Xie, and Jianlin Shi. 2026. “Copper-Based Targeted Nanocatalytic Therapeutics for Non-Small Cell Lung Cancer”. Nano-Micro Letters 18 (January):152. https://doi.org/10.1007/s40820-025-01998-5.
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