One-pot synthesis of Mn/Fe bimetal-doped metal-organic framework as multifunctional nanocarriers for esophageal cancer targeted therapy
8 affiliations
- 1Department of Gastroenterology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China
- 2Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China
- 3Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China
- 4Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250000, China
- 5Comprehensive Health Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade Nova de Lisboa, Lisboa, 1169, Portugal; Corresponding author.
- 6Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, 110004, China; Corresponding author.
- 7Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, 110004, China; Corresponding author.
- 8Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China; Corresponding author.
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 respond to acidic and GSH-rich conditions for loading ursolic acid (UA) and MTH1 siRNA (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) generation, 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.
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BibTeX
@article{ma2026onepot,
title = {{One-pot synthesis of Mn/Fe bimetal-doped metal-organic framework as multifunctional nanocarriers for esophageal cancer targeted therapy}},
author = {Jia Ma and Xin Zhang and Xiangpeng Meng and Yuhang Dai and Huaiyong Wang and Milad Ashrafizadeh and João Conde and Zhenggang Li and Enyang Yao and Wei He},
journal = {Journal of Pharmaceutical Analysis},
year = {2026},
month = sep,
doi = {10.1016/j.jpha.2026.101617},
url = {https://doi.org/10.1016/j.jpha.2026.101617},
note = {CC BY},
}
RIS
TY - JOUR
TI - One-pot synthesis of Mn/Fe bimetal-doped metal-organic framework as multifunctional nanocarriers for esophageal cancer targeted therapy
AU - Jia Ma
AU - Xin Zhang
AU - Xiangpeng Meng
AU - Yuhang Dai
AU - Huaiyong Wang
AU - Milad Ashrafizadeh
AU - João Conde
AU - Zhenggang Li
AU - Enyang Yao
AU - Wei He
PY - 2026
DA - 2026/09/01
JO - Journal of Pharmaceutical Analysis
DO - 10.1016/j.jpha.2026.101617
UR - https://doi.org/10.1016/j.jpha.2026.101617
AB - 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 respond to acidic and GSH-rich conditions for loading ursolic acid (UA) and MTH1 siRNA (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) generation, 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.
SN - 2095-1779
SN - 2214-0883
ER -