Novel lipid-polymer hybrid nanoparticles for siRNA delivery and IGF-1R gene silencing in breast cancer cells

Abstract

BackgroundDelivery of siRNA has been one of the major challenges to application of siRNA therapeutics. Polymer/lipid hybrid nanoparticles (HNPs) combine the advantages of both polymeric and liposomal carriers with remarkable properties for efficient siRNA encapsulation and delivery. ObjectiveHerein, PLA-PEG-PLA/lipid hybrid nanoparticles were fabricated and utilized for siRNA encapsulation. Transfection efficiency of complex HNPs/siRNA was investigated in MCF7 breast cancer cells. MethodsPLA-PEG-PLA copolymer was synthesized by ring opening polymerization and its hybridization with cationic lipid was performed using sonication method. Quality controls and HNP cytotoxicity were determined using DLS, AFM, SEM, and MTT assay, respectively. Cellular uptake of HNP/siRNA complex was investigated by flow cytometry and fluorescence microscope. Silencing activity of HNPs/siRNA complexes was analyzed using semi-quantitative RT-PCR. ResultsFabricated HNPs exhibited improved biocompatibility compared to the cognate lipid nanoparticles and showed high siRNA encapsulation efficiency (80% ± 5). HNPs were capable of transferring of IGF-1R-siRNA into MCF7 cells, which resulted in expression down regulation of IGF-1R gene (70% ± 3). ConclusionThe excellent cyto-compatibility, high cellular uptake, and remarkable gene silencing ability made HNPs promising carriers for efficient siRNA delivery.