Engineering Human Epidermal Growth Receptor 2-Targeting Hepatitis B Virus Core Nanoparticles for siRNA Delivery in Vitro and in Vivo.

ABSTRACT: Hepatitis B virus core (HBc) particles acquire the capacity to disassemble and reassemble in a controlled manner, allowing entrapment and delivery of drugs and macromolecules to cells. HBc particles are made of 180-240 copies of 21 kDa protein monomers, assembled into 30-34 nm diameter icosahedral particles. In this study, we aimed at formulating HBc particles for the delivery of siRNA for gene silencing in vitro and in vivo. We have previously reported recombinant HBc particles expressing Z_HER2 affibodies, specifically targeting human epidermal growth receptor 2 (HER2)-expressing cancer cells (Z_HER2-?HBc). siRNA was encapsulated within the Z_HER2-?HBc particles following disassembly and reassembly. The Z_HER2-?HBc-siRNA hybrids were able to secure the encapsulated siRNA from serum and nucleases in vitro. Enhanced siRNA uptake in HER2-expressing cancer cells treated with Z_HER2-?HBc-siRNA hybrids was observed compared to the nontargeted HBc-siRNA hybrids in a time- and dose-dependent manner. A successful in vitro polo-like kinase 1 (PLK1) gene knockdown was demonstrated in cancer cells treated with Z_HER2-?HBc-siPLK1 hybrids, to levels comparable to commercial transfecting reagents. Interestingly, Z_HER2-?HBc particles exhibit intrinsic capability of reducing the solid tumor mass, independent of siPLK1 therapy, in an intraperitoneal tumor model following intraperitoneal injection.

SUBMITTER: Suffian IFM 

PROVIDER: S-EPMC6312360 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature