Multifunctional H2S-activated metal-organic framework systems for targeted colorectal cancer imaging and synergistic copper-induced tumor regression

Nannan Zheng; Qinghui Wang; Zhiyue Cao; Chao Yu; Renkai Zhang; Kaiyan Xiang; Haoguang Wu; Kai Li; Qianqian Ni; Qiuyue Ma; Jing Mu; Xiaoyuan Chen; Liangcan He; Shaoqin Liu

doi:10.1002/bmm2.70029

BMEMat ›› 2026, Vol. 4 ›› Issue (1) :e70029 DOI: 10.1002/bmm2.70029

RESEARCH ARTICLE

Multifunctional H₂S-activated metal-organic framework systems for targeted colorectal cancer imaging and synergistic copper-induced tumor regression

Nannan Zheng ¹^,²
, Qinghui Wang ²^,³
, Zhiyue Cao ¹^,²
, Chao Yu ¹
, Renkai Zhang ¹
, Kaiyan Xiang ⁴
, Haoguang Wu ⁴
, Kai Li ¹^,²
, Qianqian Ni ⁵^,⁶^,⁷
, Qiuyue Ma ¹^,²
, Jing Mu ⁸
, Xiaoyuan Chen ⁵^,⁶^,⁷
, Liangcan He ¹^,²
, Shaoqin Liu ¹^,²

Author information +

¹. Key Laboratory of Microsystems and Microstructures Manufacturing (Ministry of Education), School of Medicine and Health, Harbin Institute of Technology, Harbin, China

². Zhengzhou Research Institute, Harbin Institute of Technology, Zhengzhou, China

³. School of Life Science and Technology, Harbin Institute of Technology, Harbin, China

⁴. Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China

⁵. Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore

⁶. Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

⁷. Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

⁸. Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen, China

jing.mu@pkuszh.com

liangcanhe@hit.edu.cn

shaoqinliu@hit.edu.cn

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Abstract

Stimuli-responsive nanomaterials offer significant potential for enhancing diagnostic accuracy, optimizing therapeutic efficacy, and advancing precision theranostics. Hydrogen sulfide (H₂S) was found to be upregulated in colorectal cancer, which endows it with an ideal endogenous trigger for tumor targeting. Here, we introduce a novel class of H₂S-activated metal-organic framework (MOF) systems specifically designed for targeted colorectal cancer imaging and synergistic copper-induced tumor regression. The Cu-MOF nanoplatform demonstrated a rapid response to H₂S at the tumor site, producing copper sulfide with strong near infrared absorption and activated PA signals. In vivo studies demonstrated remarkable tumor inhibition in an orthotopic colon cancer model with minimal side effects. The copper-based MOFs theranostic nanosystem effectively reduced protein lipoylation and Fe-S cluster protein levels (FDX1), triggering cuproptosis. This study presents a novel strategy for designing multifunctional nanoparticles for synergistic PA/CDT/PTT/cuproptosis theranostics.

Keywords

colorectal cancer / Cu-MOFs-DOX / H₂S response / photoacoustic imaging / photothermal therapy

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Nannan Zheng, Qinghui Wang, Zhiyue Cao, Chao Yu, Renkai Zhang, Kaiyan Xiang, Haoguang Wu, Kai Li, Qianqian Ni, Qiuyue Ma, Jing Mu, Xiaoyuan Chen, Liangcan He, Shaoqin Liu. Multifunctional H₂S-activated metal-organic framework systems for targeted colorectal cancer imaging and synergistic copper-induced tumor regression. BMEMat, 2026, 4 (1) : e70029 DOI:10.1002/bmm2.70029

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