Abstract
Small interfering RNAs (siRNAs) are promising as therapeutics for intractable diseases such as cancer. However, efficient and safe delivery of siRNAs in vivo remains a challenge. Polymer-lipid hybrid nanoparticles (P/LNPs) have been evaluated for therapeutic delivery of siRNA. In this study, a microfluidic hydrodynamic focusing (MF) system was used to prepare P/LNPs loaded with VEGF siRNA. P/LNPs made by MF were smaller in particle size and had narrower size distribution compared to P/LNPs formed by bulk mixing (BM). MF-synthesized P/LNPs demonstrated low vehicle cytotoxicity and potent tumor cell inhibition in vitro. In addition, P/LNPs produced by the microfluidic chip exhibited prolonged blood circulation and increased AUC after i.v. injection compared to free siRNA. Furthermore, P/LNPs synthesized by MF induced greater down-regulation of VEGF mRNA and protein levels as well as greater tumor inhibition in a xenograft tumor model. Taken together, P/LNPs prepared by MF have been shown to be an effective and safe therapeutic siRNA delivery system for cancer treatment both in vitro and in vivo.