RESUMEN
Amylose is a promising nanocarrier for gene delivery in terms of its good biocompatibility and high transfection efficiency. Small interfering RNA against survivin (survivin-siRNA) can cause tumor apoptosis by silencing a hepatocellular carcinoma (HCC)-specific gene at the messenger RNA level. In this study, we developed a new class of folate-functionalized, superparamagnetic iron oxide (SPIO)-loaded cationic amylose nanoparticles to deliver survivin-siRNA to HCC cells. The cellular uptake of nanocomplexes, cytotoxicity, cell apoptosis, and gene suppression mediated by siRNA-complexed nanoparticles were tested. The results demonstrated that folate-functionalized, SPIO-loaded cationic amylose nanoparticles can mediate a specific and safe cellular uptake of survivin-siRNA with high transfection efficiency, resulting in a robust survivin gene downregulation in HCC cells. The biocompatible complex of cationic amylose could be used as an efficient, rapid, and safe gene delivery vector. Upon SPIO loading, it holds a great promise as a theranostic carrier for gene therapy of HCC.
RESUMEN
PURPOSE: To evaluate the usefulness of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the assessment of nonalcoholic fatty liver disease (NAFLD) severity. MATERIALS AND METHODS: Liver DCE-MRI at 3.0T was performed in 36 adult Sprague-Dawley rats with methionine choline-deficient diet-induced NAFLD and 10 untreated control rats. Pharmacokinetic parameters of DCE-MRI including Ktrans , Kep , Ve , Vp , and hepatic portal index (HPoI) were measured using the dual-input extended Tofts model. Animals were categorized as normal (n = 10), simple steatosis (SS, n = 11), borderline nonalcoholic steatohepatitis (bNASH, n = 20), and NASH (n = 5) subgroups according to the NAFLD activity score system, and classified into F0 (n = 24), F1 (n = 11), F2 (n = 7), and F3 (n = 4) subgroups according to an established scoring system. DCE-MRI parameters were compared. Receiver operating characteristic analyses were performed to assess the diagnostic performance of various DCE-MRI parameters in grading NAFLD activity and staging liver fibrosis. RESULTS: Ktrans and HPoI were elevated with increasing severity of NAFLD activity and increased fibrosis stage. The areas under the receiver operating characteristic curve (AUROCs) of HPoI ranged from 0.895-0.951 for discriminating between different grades of NAFLD activity, and the AUROC was 0.852 for discriminating F0 stage from overall F1-F3 stages. The AUROC of Ktrans for discriminating non-NASH from bNASH and NASH groups was 0.968, and 0.898 for discriminating between normal and overall fibrosis groups. CONCLUSION: DCE-MRI may play a role in assessing NAFLD severity. LEVEL OF EVIDENCE: 1 J. MAGN. RESON. IMAGING 2017;45:1485-1493.
