Reverse magnetic resonance tuning nanoplatform with heightened sensitivity for non-invasively multiscale visualizing ferroptosis-based tumor sensitization therapy

Yi Zhu; Jiali Deng; Hongwei Lu; Zhu Mei; Ziwei Lu; Jiajing Guo; An Chen; Rong Cao; Xinyi Ding; Jingyi Wang; Helen Forgham; Ruirui Qiao; Zhongling Wang

doi:10.1016/j.biomaterials.2024.122935

Reverse magnetic resonance tuning nanoplatform with heightened sensitivity for non-invasively multiscale visualizing ferroptosis-based tumor sensitization therapy

Biomaterials. 2024 Oct 30:315:122935. doi: 10.1016/j.biomaterials.2024.122935. Online ahead of print.

Authors

Yi Zhu¹, Jiali Deng², Hongwei Lu³, Zhu Mei⁴, Ziwei Lu⁵, Jiajing Guo¹, An Chen¹, Rong Cao¹, Xinyi Ding¹, Jingyi Wang², Helen Forgham⁶, Ruirui Qiao⁶, Zhongling Wang⁷

Affiliations

¹ Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
² Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China; School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.
³ Department of Biomedical Engineering, College of Engineering, Shantou University, Shantou, 515063, China.
⁴ Shanghai Key Laboratory of Pancreatic Diseases, Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
⁵ Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China.
⁶ Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, 4072, Australia.
⁷ Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China. Electronic address: zlwang138136@126.com.

PMID: 39489017
DOI: 10.1016/j.biomaterials.2024.122935

Abstract

Ferroptosis-based therapy has garnered considerable attention for its ability to kill drug-resistant cancer cells. Consequently, it holds great significance to assess the therapeutic outcomes by monitoring ferroptosis-related biomarkers, which enables the provision of real-time pathological insights into disease progression. Nevertheless, conventional imaging technology suffers from limitations including reduced sensitivity and difficulty in achieving real-time precise monitoring. Here, we report a tumor acidic-microenvironment-responsive nanoplatform with "Reverse Magnetic Resonance Tuning (ReMRT)" property and effective combined chemodynamic therapy (CDT) through the loading of chemotherapeutic drugs. This reverse MR mapping change is correlated with iron ion, reactive oxygen species (ROS) generation and drug release, etc., contributing to the precise monitoring of chemo-CDT effectiveness. Furthermore, the ReMRT nanoplatform presents as a highly efficacious combined chemo-CDT agent, and when this nanoplatform is used in conjunction with the "Area Reconstruction" method, it can afford a significant sensitivity (95.1-fold) in multiscale visualization of therapeutic, compared with the conventional MR R₁/R₂ values. The high-sensitive biological quantitative imaging provides a novel strategy for MR-guided multiscale dynamic tumor-related ferroptosis therapy.

Keywords: Ferroptosis directed chemo dynamic therapy; High sensitivity; Reverse magnetic resonance tuning nanoprobe; Visualization of ferroptosis-related biomarkers.