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

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 ZHER2 affibodies, specifically targeting human epidermal growth receptor 2 (HER2)-expressing cancer cells (ZHER2 -ΔHBc). siRNA was encapsulated within the ZHER2 -ΔHBc particles following disassembly and reassembly. The ZHER2 -ΔHBc-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 ZHER2 -ΔHBc-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 ZHER2 -ΔHBc-siPLK1 hybrids, to levels comparable to commercial transfecting reagents. Interestingly, ZHER2 -ΔHBc particles exhibit intrinsic capability of reducing the solid tumor mass, independent of siPLK1 therapy, in an intraperitoneal tumor model following intraperitoneal injection.