Ligand-targeted bacterial minicells: Futuristic nano-sized drug delivery system for the efficient and cost effective delivery of shRNA to cancer cells.

In this study, shRNA against VEGFA was packaged in bacterial minicells and surface of minicells was modified with folic acid. Analysis of cellular internalization revealed that folic acid conjugated minicells internalized through receptor mediated endocytosis in folate and PSMA receptor positive KB and LNCaP cells, respectively. In contrast, A549 (folate receptor negative) cells showed minute internalization. In vitro delivery of FAminicellsVEGFA significantly reduced the expression of VEGFA mRNA in KB and LNCaP cells whereas expression of VEGFA remained unaltered in A549 cells. FAminicellsVEGFA significantly reduced tumor volume in mice bearing KB and LNCaP xenograft. On contrary, gradual increase in the tumor volume was recorded in A549 xenograft. FAminicellsVEGFA significantly silenced the VEGFA mRNA in KB and LNCaP xenograft. Expression of VEGFA remained same in FAminicellsVEGFA delivered A549 xenograft. In vivo biodistribution study showed that majority of FAminicellsVEGFA were localized in the tumor followed by intravenous administration.