Polymer nanoparticle-mediated delivery of microRNA 145: A potential therapeutic strategy for hepatocellular carcinoma in an experimental model.

MicroRNA-145 (miR-145) plays a critical regulatory role in the pathogenesis and clinical management of various malignancies, particularly hepatocellular carcinoma (HCC). This study aimed to evaluate the therapeutic efficacy of polymer nanoparticle-mediated miR-145 delivery in an experimental model of HCC. Eighty male Balb/C mice were randomized into four distinct groups: a normal control group, an HCC group, a group receiving free miR-145, and a group treated with polymer-conjugated miR-145. Following the intervention, hepatic expression levels of SENP1, P70-S6K1, and FSCN were quantified using real-time PCR. Additionally, serum concentrations of alpha-fetoprotein (α-AFP), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-α) were measured via ELISA, complemented by a histopathological evaluation of liver tissue. The results showed that pathological controls exhibited a profound elevation (P< 0.001) in hepatic SENP1, P70S6K1, and FSCN expression, along with significantly higher serum levels of AFP, VEGF, and TNF-α compared with normal controls. While monotherapy with miR-145 successfully down-regulated these tissue biomarkers (P < 0.01) and reduced serum proteins (P < 0.001), the polymer-conjugated miR-145 formulation demonstrated superior therapeutic efficacy. This nanoparticle-mediated delivery yielded the most pronounced reductions compared with the free miR-145 group (P < 0.001 for P70S6K1 and FSCN; P < 0.05 for SENP1). These molecular improvements were further validated by histopathological findings, which showed a marked restoration of liver tissue architecture in the treated groups. In conclusion, utilizing polymer nanoparticles for delivering miR-145 substantially enhances its therapeutic impact, positioning this formulation as a highly promising targeted intervention for the treatment of hepatocellular carcinoma.