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Updated: Jul 21, 2025
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Intravenous Delivery of miR-21 Inhibitor in Mice With Head and Neck Squamous Cell Carcinoma
Hajime Ishinaga1, Taro Yasuma2, Corina N D'Alessandro-Gabazza2
1Department of Otorhinolaryngology-Head & Neck Surgery, Mie University Graduate School of Medicine, Mie, Japan; hajime@med.mie-u.ac.jp.
Background/Aim:
Synthetic miRNA inhibitors have recently attracted considerable interest as potential therapeutic agents for head and neck squamous cell carcinoma. However, due to the lack of evidence, no attempts have been made to deliver these inhibitors intravenously for squamous cell carcinoma.
Materials And Methods:
This study investigated whether intravenous administration of a miR-21 inhibitor with lipid nanoparticles could suppress HNSCC in xenograft mice. Head and neck squamous cell carcinoma xenograft mice were intravenously injected with Invivofectamine 3.0® containing either a miR-21 inhibitor or a control inhibitor, using a modified protocol for nucleic acid encapsulation. Quantitative PCR was used to measure the expression level of intratumoral miR-21. And TdT-mediated dUTP nick-end labeling (TUNEL) immunohistochemistry was used to assess cell death.
Results:
Intravenous injection of miR-21 inhibitor significantly inhibited head and neck squamous cell carcinoma growth and miR-21 expression in tumor tissue compared to the control inhibitor. TUNEL assay showed significant apoptosis of tumor cells after intravenous administration of miR-21 inhibitor.
Conclusion:
Intravenous delivery of a miR-21 inhibitor with lipid nanoparticles is a promising approach for miRNA-targeted therapy of head and neck squamous cell carcinoma.
Insights
Intravenous delivery of a miR-21 inhibitor using lipid nanoparticles effectively suppressed head and neck squamous cell carcinoma (HNSCC) growth and induced tumor cell death in mice.
Area of Science:
- Oncology
- Molecular Biology
- Nanomedicine
Background:
- Synthetic microRNA (miRNA) inhibitors show therapeutic potential for head and neck squamous cell carcinoma (HNSCC).
- Intravenous delivery of these inhibitors for HNSCC has not been previously investigated due to limited evidence.
Purpose of the Study:
- To investigate the efficacy of intravenous administration of a miR-21 inhibitor encapsulated in lipid nanoparticles for suppressing HNSCC.
- To evaluate the impact of this treatment on tumor growth, miR-21 expression, and apoptosis in a xenograft mouse model.
Main Methods:
- Head and neck squamous cell carcinoma xenograft mice received intravenous injections of lipid nanoparticles containing either a miR-21 inhibitor or a control inhibitor.
- Quantitative PCR was employed to measure intratumoral miR-21 expression levels.
- Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was used to assess tumor cell apoptosis.
Main Results:
- Intravenous administration of the miR-21 inhibitor significantly inhibited HNSCC tumor growth compared to the control.
- A significant reduction in miR-21 expression within tumor tissues was observed post-treatment.
- TUNEL assay confirmed significant apoptosis in tumor cells following the intravenous delivery of the miR-21 inhibitor.
Conclusions:
- Intravenous delivery of miR-21 inhibitors via lipid nanoparticles represents a promising strategy for miRNA-targeted therapy in head and neck squamous cell carcinoma.
- This approach warrants further investigation for clinical applications in HNSCC treatment.
