Nanomolecular silencing of TSC۲۲D۴ mRNA via a DNAsome-siRNA for enhancing insulin sensitization in hepatocytes

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 ۲ 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 ۲۲ D۴ (TSC۲۲D۴), 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 TSC۲۲D۴ expression in HepG۲ 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 HepG۲ cells.Results: Findings indicated successful fabrication of the DNAsome nanocarriers, although aggregation was observed at higher concentrations, yielding nanoparticle sizes between ۱۱۶ and ۷۴۰ nm. Real-time PCR results confirmed effective siRNA targeting, significant cellular uptake of the nanocomplexes, and successful silencing of TSC۲۲D۴ 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.

کلیدواژه ها:

DNAsome ، HepG۲ ، insulin resistance ، siRNA ، TSC۲۲D۴