Nanomolecular silencing of TSC22D4 mRNA via a DNAsome-siRNA for enhancing insulin sensitization in hepatocytes

Document Type : Original Article

Authors

1 Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

2 Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran

3 Research Center of Immunogenetics, Mazandaran University of Medical Sciences, Sari, Iran

4 Research Center for Diabetes, Mazandaran University of Medical Sciences, Sari, Iran

5 The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran

6 Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran

10.22038/ijbms.2024.81998.17744

Abstract

Objective(s): Insulin resistance (IR) is a critical component of metabolic syndrome, primarily linked to obesity. It contributes to impaired glucose metabolism, beta-cell dysfunction, and the onset of type 2 diabetes. This study aimed to develop a DNAsome nanocarrier designed for the targeted delivery of small interfering RNA (siRNA) to inhibit mRNA of Transforming growth factor beta-like Stimulated Clone 22 D4 (TSC22D4), thereby enhancing insulin sensitivity in hepatocytes. 
Materials and Methods: The DNAsome was constructed using Y-DNA building blocks derived from three distinct DNA oligonucleotides. Its structural characteristics were analyzed through atomic force microscopy (AFM). The functional efficacy of the DNAsome in delivering siRNA was evaluated by measuring its cellular uptake and ability to down-regulate TSC22D4 expression in HepG2 cells via real-time PCR. Additionally, the cytotoxicity and safety of both the DNAsome and the DNAsome-siRNA complexes were assessed using the MTT assay on HepG2 cells.
Results: Findings indicated successful fabrication of the DNAsome nanocarriers, although aggregation was observed at higher concentrations, yielding nanoparticle sizes between 116 and 740 nm. Real-time PCR results confirmed effective siRNA targeting, significant cellular uptake of the nanocomplexes, and successful silencing of TSC22D4 expression. 
Conclusion: This study suggests that DNAsome-based siRNA delivery systems hold promise for improving insulin sensitivity and addressing IR associated with obesity and metabolic syndrome.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 28, Issue 3
March 2025
Pages 385-392

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