Magnetic field-controlled nanozymes effectively overcome therapeutic limitations in tumor ferroptosis therapy
- 1Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University
Abstract
Iron oxide nanozymes with intrinsic peroxidase-like activity and excellent biosafety are considered ideal agents for inducing tumor ferroptosis. However, their practical catalytic efficiency is often constrained by an inherent delocalized electronic structure and the restrictive tumor antioxidant microenvironment. Herein, we report a magnetic field-mediated strategy to synthesize ultra-small superparamagnetic manganese-doped iron oxide (USMIO) nanoparticles with precisely tailored multi-enzyme activities (denoted as MUSMIO). The magnetic field in situ generated abundant oxygen vacancies and optimized the Mn/Fe coordination environment, significantly boosting electron transfer and catalytic performance. MUSMIO exhibited robust pH-responsive peroxidase-like activity with a hydroxyl radical yield ∼5.86-fold higher than pure ultra-small superparamagnetic iron oxide (USIO) and ∼2.43-fold higher than USMIO, together with favorable catalase-, glutathione oxidase-, and nicotinamide adenine dinucleotide phosphate oxidase-like activities. This synergistic multi-enzyme cascade efficiently blocked glutathione regeneration, relieved tumor hypoxia, and triggered a sustained hydroxyl radical storm to drive extensive lipid peroxidation and selective ferroptosis in cancer cells, while exhibiting negligible toxicity to normal cells. In a murine breast cancer model, MUSMIO achieved complete tumor regression with no recurrence, and prolonged the median survival time of mice with excellent biosafety. This work provides a generalizable physical-field-assisted route for designing high-performance multi-enzyme mimetic nanozymes for targeted tumor therapy. Graphical Abstract
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BibTeX
@article{hu2026magnetic,
title = {{Magnetic field-controlled nanozymes effectively overcome therapeutic limitations in tumor ferroptosis therapy}},
author = {Xin-Yue Hu and Xiao-Yan Tang and Cong Liu and Xiao-Xiao Gong and Shan-Shan Rao and Chun-Yuan Chen and Zhen-Xing Wang and Hui Xie and Hong-Ji Liu},
journal = {Journal of Nanobiotechnology},
year = {2026},
month = jul,
doi = {10.1186/s12951-026-04796-2},
url = {https://doi.org/10.1186/s12951-026-04796-2},
note = {CC BY},
}
RIS
TY - JOUR
TI - Magnetic field-controlled nanozymes effectively overcome therapeutic limitations in tumor ferroptosis therapy
AU - Xin-Yue Hu
AU - Xiao-Yan Tang
AU - Cong Liu
AU - Xiao-Xiao Gong
AU - Shan-Shan Rao
AU - Chun-Yuan Chen
AU - Zhen-Xing Wang
AU - Hui Xie
AU - Hong-Ji Liu
PY - 2026
DA - 2026/07/01
JO - Journal of Nanobiotechnology
DO - 10.1186/s12951-026-04796-2
UR - https://doi.org/10.1186/s12951-026-04796-2
AB - Iron oxide nanozymes with intrinsic peroxidase-like activity and excellent biosafety are considered ideal agents for inducing tumor ferroptosis. However, their practical catalytic efficiency is often constrained by an inherent delocalized electronic structure and the restrictive tumor antioxidant microenvironment. Herein, we report a magnetic field-mediated strategy to synthesize ultra-small superparamagnetic manganese-doped iron oxide (USMIO) nanoparticles with precisely tailored multi-enzyme activities (denoted as MUSMIO). The magnetic field in situ generated abundant oxygen vacancies and optimized the Mn/Fe coordination environment, significantly boosting electron transfer and catalytic performance. MUSMIO exhibited robust pH-responsive peroxidase-like activity with a hydroxyl radical yield ∼5.86-fold higher than pure ultra-small superparamagnetic iron oxide (USIO) and ∼2.43-fold higher than USMIO, together with favorable catalase-, glutathione oxidase-, and nicotinamide adenine dinucleotide phosphate oxidase-like activities. This synergistic multi-enzyme cascade efficiently blocked glutathione regeneration, relieved tumor hypoxia, and triggered a sustained hydroxyl radical storm to drive extensive lipid peroxidation and selective ferroptosis in cancer cells, while exhibiting negligible toxicity to normal cells. In a murine breast cancer model, MUSMIO achieved complete tumor regression with no recurrence, and prolonged the median survival time of mice with excellent biosafety. This work provides a generalizable physical-field-assisted route for designing high-performance multi-enzyme mimetic nanozymes for targeted tumor therapy. Graphical Abstract
SN - 1477-3155
ER -