Tumor microenvironment-responsive manganese nanocarriers for on-demand release of methotrexate and DNAzyme in MiR-155-driven cervical cancer.
5 affiliations
- 1Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.
- 2Institute of Medical Engineering, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, China.
- 3Department of Nephrology, The First People's Hospital of Zigong, Zigong, Sichuan, 643000, China.
- 4Department of Critical Care Medicine, The First People's Hospital of Zigong, Zigong, Sichuan, 643000, China.
- 5Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China.
Abstract
Cervical cancer is a prevalent form of cancer that affects women on a global scale. MicroRNA-155 (miR-155) has been identified as a key player in cervical cancer, with its over-expression signifying a promising target for therapeutic interventions. However, the molecular mechanisms by which miR-155 contributes to the invasive progression of cervical cancer, as well as miRNA-based therapeutic approaches, remain to be elucidated. To address the issues, we initially investigated the functional role of miR-155 in cervical cancer progression. In vitro and in vivo results demonstrated that miR-155 was closely associated with the malignant progression of cervical cancer through regulation of the epithelial-mesenchymal transition (EMT) process, specifically by directly targeting ZFPM2 protein, thereby exerting oncogenic effects. Based on these findings, we designed manganese-based composite agents, namely MnO₂@PDA-DNAzyme-substrate-methotrexate nanoparticles (MPDM NPs), for simultaneous miRNA imaging and chemotherapy toward cervical cancer. The MPDM NPs exhibited favorable biocompatibility and tumor microenvironment (TME) responsive release behavior, allowing controlled release of Mn²⁺, methotrexate (MTX), and DNAzyme probes for miR-155 detection and therapeutic intervention. In vivo studies with tumor-bearing mice indicated that the MPDM NPs could effectively target tumors. The Mn²⁺-activate miRNA imaging achieved a detection limit for miR-155 of 0.3 nM. Moreover, the drug MTX enabled tumor chemotherapy by regulating the EMT process. This, in turn, has resulted in an impressive tumor inhibition rate of 86.2%. This proposed strategy indicated significant potential for the advancement of precision theranostics in the context of cervical cancer.
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BibTeX
@article{yang2026tumor,
title = {{Tumor microenvironment-responsive manganese nanocarriers for on-demand release of methotrexate and DNAzyme in MiR-155-driven cervical cancer.}},
author = {Zeping Yang and Ling Zhang and Zhenlong Wang and Chong Hu and Deqiang Ruan and Fan Zhang and Bin Guo and Yingli Shen and Fu Wang},
journal = {Materials today. Bio},
year = {2026},
month = oct,
doi = {10.1016/j.mtbio.2026.103747},
url = {https://europepmc.org/article/MED/42903640},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Tumor microenvironment-responsive manganese nanocarriers for on-demand release of methotrexate and DNAzyme in MiR-155-driven cervical cancer.
AU - Zeping Yang
AU - Ling Zhang
AU - Zhenlong Wang
AU - Chong Hu
AU - Deqiang Ruan
AU - Fan Zhang
AU - Bin Guo
AU - Yingli Shen
AU - Fu Wang
PY - 2026
DA - 2026/10/09
JO - Materials today. Bio
DO - 10.1016/j.mtbio.2026.103747
UR - https://europepmc.org/article/MED/42903640
AB - Cervical cancer is a prevalent form of cancer that affects women on a global scale. MicroRNA-155 (miR-155) has been identified as a key player in cervical cancer, with its over-expression signifying a promising target for therapeutic interventions. However, the molecular mechanisms by which miR-155 contributes to the invasive progression of cervical cancer, as well as miRNA-based therapeutic approaches, remain to be elucidated. To address the issues, we initially investigated the functional role of miR-155 in cervical cancer progression. In vitro and in vivo results demonstrated that miR-155 was closely associated with the malignant progression of cervical cancer through regulation of the epithelial-mesenchymal transition (EMT) process, specifically by directly targeting ZFPM2 protein, thereby exerting oncogenic effects. Based on these findings, we designed manganese-based composite agents, namely MnO₂@PDA-DNAzyme-substrate-methotrexate nanoparticles (MPDM NPs), for simultaneous miRNA imaging and chemotherapy toward cervical cancer. The MPDM NPs exhibited favorable biocompatibility and tumor microenvironment (TME) responsive release behavior, allowing controlled release of Mn²⁺, methotrexate (MTX), and DNAzyme probes for miR-155 detection and therapeutic intervention. In vivo studies with tumor-bearing mice indicated that the MPDM NPs could effectively target tumors. The Mn²⁺-activate miRNA imaging achieved a detection limit for miR-155 of 0.3 nM. Moreover, the drug MTX enabled tumor chemotherapy by regulating the EMT process. This, in turn, has resulted in an impressive tumor inhibition rate of 86.2%. This proposed strategy indicated significant potential for the advancement of precision theranostics in the context of cervical cancer.
SN - 2590-0064
ER -