Preparation and characterization of silk fibroin/oligochitosan nanoparticles for siRNA delivery

摘要

siRNA therapy offers hope treating diseases caused by genetic defects as well as viral infections and cancers, although it has been limited by the low stability of siRNA and its rapid degradation in the presence of nucleases as well as its low cellular uptake. In this study, oligochitosan (OC) combined with silk fibroin (SF) was formulated and proposed as a novel carrier for siRNA. The obtained SF/OC/siRNA nanoparticles (NPs) were characterized according to their physicochemical properties, such as their size, zeta potential, loading efficiency, stability, cytotoxicity, cellular uptake and transfection efficiency, and their properties were compared with those of OC polyplexes. The mean diameter of SF/OC/siRNA NPs was not significantly different compared to polyplexes, and the particle size ranged between 250 and 450 nm. Increased amounts of SF in NPs enhanced their loading efficiency, and NPs showed excellent stability in the presence of FBS and heparin compared with OC polyplexes. Additionally, MTT assays demonstrated that SF/OC/siRNA NPs had lower cytotoxicity. NPs showed better gene silencing with or without FBS, which could be attributed to increased loading efficiency, serum stability and cellular uptake. These properties suggest that SF/OC/siRNA NPs have a strong potential as gene carriers. (C) 2015 Elsevier B.V. All rights reserved.