Stimulation with polyinosinic-polycytidylic acid (poly(I:C)) encapsulated within novel pH-sensitive switchable liposomes leads to a faster and more potent interferon response

We have shown that selective stimulation of the interferon-based antiviral response in airway epithelial cells is feasible with liposome-encapsulated poly(I:C), involving the RIG-I / MAVS pathway (J Immunol 2015;195:2829-41). This requires efficient liposome-mediated intracellular poly(I:C) uptake. Here we tested whether poly(I:C) uptake and interferon stimulation can be enhanced by encapsulation of poly(I:C) within novel pH-sensitive switchable liposomes. Airway epithelial cell lines 16HBE14o- and CFBE41o- were stimulated with poly(I:C) encapsulated within novel liposomes (prepared using switchable lipids, DSPC, cholesterol and DSPE-PEG2000 at molar ratios of 50:10:37.5:2.5). Poly(I:C) encapsulated within commercial liposomes (Lyovec) served as control. Outcomes were expression of interferon-β and λ1 mRNAs (qPCR) at 0, 2, 4, and 8 hours of stimulation, and poly(I:C) uptake, visualized using rhodamine-labelled novel liposomes. In both cell lines, poly(I:C)+novel liposomes up-regulated both interferon mRNAs significantly faster and more potently than poly(I:C)+Lyovec, with respective mRNA peaks observed at 2 – 4 hours vs. 8 hours of stimulation (p Krieble and Gosselin Foundations. Cells: D. Gruenert.