Paper Title
Therapeutic Effect of Polymer Nanoparticle-Conjugated Microrna-145 on a Murine Model of Hepatocellular Carcinoma

Abstract
Several studies revealed specific miRNA signatures in hepatocellular carcinoma (HCC) that could be exploited as potential therapeutic targets. Among these miRNAs, miR-145, which is found to be associated with the clinicopathological features, histological grade, and prognosis of the disease. So, this study was designed to study the therapeutic effect of miR-145 alone and in conjugation with polymer nanoparticles, to extend miRNA circulating time and its stability, on an experimental model of HCC. Four groups of mice were utilized; a control group and three other groups injected with diethylnitrosamine (DEN) once/week for 12 weeks to induce HCC. Then, the 1st HCC group served as a pathological control, the 2nd HCC group was injected with free miRNA-145, and the 3rd HCC group was injected with polymer nanoparticle-conjugated miRNA-145. Then, the HCC-associated biomarkers were assessed in the serum of mice. Also, hepatic specimens were examined histopathologically. The results showed that AFP, VEGF, and TNF-α decreased significantly, in the free and the nanoconjugated-miRNA-145-treated group, compared to the HCC group. Similarly, the histopathological changes improved significantly in in the free and nanoconjugated-miRNA-145-treated group. In conclusion, administration of miRNA-145, either in a free form or in conjugation with nanoparticles, is a potential therapeutic agent against HCC.