One-pot synthesis of Mn/Fe bimetal-doped metal-organic framework as multifunctional nanocarriers for esophageal cancer targeted therapy

Jia Ma; Xin Zhang; Xiangpeng Meng; Yuhang Dai; Huaiyong Wang; Milad Ashrafizadeh; João Conde; Zhenggang Li; Enyang Yao; Wei He

doi:10.1016/j.jpha.2026.101617

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Jia Ma, Xin Zhang, Xiangpeng Meng, Yuhang Dai, Huaiyong Wang, Milad Ashrafizadeh, João Conde, Zhenggang Li, Enyang Yao, Wei He. One-pot synthesis of Mn/Fe bimetal-doped metal-organic framework as multifunctional nanocarriers for esophageal cancer targeted therapy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101617

Citation:

Jia Ma, Xin Zhang, Xiangpeng Meng, Yuhang Dai, Huaiyong Wang, Milad Ashrafizadeh, João Conde, Zhenggang Li, Enyang Yao, Wei He. One-pot synthesis of Mn/Fe bimetal-doped metal-organic framework as multifunctional nanocarriers for esophageal cancer targeted therapy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101617

Citation:

Jia Ma, Xin Zhang, Xiangpeng Meng, Yuhang Dai, Huaiyong Wang, Milad Ashrafizadeh, João Conde, Zhenggang Li, Enyang Yao, Wei He. One-pot synthesis of Mn/Fe bimetal-doped metal-organic framework as multifunctional nanocarriers for esophageal cancer targeted therapy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101617

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One-pot synthesis of Mn/Fe bimetal-doped metal-organic framework as multifunctional nanocarriers for esophageal cancer targeted therapy

doi: 10.1016/j.jpha.2026.101617

1. Department of Gastroenterology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, Liaoning, China;
2. Department of General Surgery, The Shengjing Hospital of China Medical University, Shenyang, 110004, China;
3. Department of Thoracic Surgery, The Shengjing Hospital of China Medical University, Shenyang, 110004, China;
4. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250000, China;
5. Comprehensive Health Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade Nova de Lisboa, Lisboa, 1169, Portugal;
6. Department of Anesthesiology, The Shengjing Hospital of China Medical University, Shenyang, 110004, China;
7. Department of Orthopedics, The Shengjing Hospital of China Medical University, Shenyang, 110004, China

Funds:

We would like to thank The Fourth Affiliated Hospital of China Medical University, The Shengjing Hospital of China Medical University, Shandong First Medical University and Shandong Academy of Medical Sciences, NOVA Medical School, and Yangzhou University for providing a research platform, which laid the foundation for the smooth progress of the project.

Received Date: Mar. 25, 2025
Accepted Date: Mar. 26, 2026
Rev Recd Date: Mar. 24, 2026
Available Online: Mar. 28, 2026

Abstract

Abstract

Chemodynamic therapy (CDT) offers new opportunities to eliminate cancer by killing tumor cells through the production of toxic hydroxyl radicals (·OH) in the tumor region. However, the efficiency of CDT is severely hampered by insufficient levels of hydrogen peroxide and large amounts of glutathione (GSH) in tumor cells. To address this issue, we developed Mn/Fe bimetallic metal-organic framework (MnFe-MOF) nanocarriers that could intelligently respond to the tumor microenvironment for loading ursolic acid (UA) and siMTH1, followed by surface modification with hyaluronic acid (HA). Finally, a nanoparticle named UA/siMTH1@MnFe-MOF@HA was developed for the treatment of esophageal cancer. Benefiting from HA-coated encapsulation, UA/siMTH1@MnFe-MOF@HA achieved Kyse-30 cell targeting and slow release of UA/siMTH1. The Mn/Fe ions doped in the nanoframework catalyzed the Fenton reaction in the tumor microenvironment with acidic pH and overexpression of GSH to promote reactive oxygen species (ROS) eruption, and further amplified oxidative stress by consuming GSH, resulting in cell damage. Moreover, siMTH1 released by the nanoparticles can cause DNA damage and induce cellular senescence to kill cancer cells, while the released UA can induce G1 cell cycle arrest to inhibit cell proliferation, synergistically enhancing the therapeutic effect. UA/siMTH1@MnFe-MOF@HA exhibited outstanding tumor suppression in vitro and in vivo, with negligible systemic toxicity. This transition metal-doped multifunctional MOF enabled efficient CDT and provides a promising paradigm for esophageal cancer therapy.
- Chemodynamic therapy,
- metal ion,
- nanoparticle,
- esophageal cancer

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References(45)

References

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