[Show abstract][Hide abstract] ABSTRACT: Cationic liposomes have emerged as a novel adjuvant and antigen delivery system to enhance vaccine efficacy. However, the role of surface charge density in cationic liposome-regulated immune responses has not yet been elucidated. In the present study, we prepared a series of DOTAP/DOPC cationic liposomes with different surface densities by incorporating varying amounts of DOPC (a neutral lipid) into DOTAP (a cationic lipid). The results showed that DOTAP/DOPC cationic liposome-regulated immune responses relied on the surface charge density, and might occur through ROS signaling. The liposomes with a relatively high charge density, such as DOTAP/DOPC 5:0 and 4:1 liposomes, potently enhanced dendritic cell maturation, ROS generaion, antigen uptake, as well as the production of OVA-specific IgG2a and IFN-γ. In contrast, low-charge liposomes, such as DOTAP/DOPC 1:4 liposome, failed to promote immune responses even at high concentrations, confirming that the immunoregulatory effect of cationic liposomes is mostly attributable to their surface charge density. Moreover, the DOTAP/DOPC 1:4 liposome suppressed anti-OVA antibody responses in vivo. Overall, maintaining an appropriate surface charge is crucial for optimizing the adjuvant effect of cationic liposomes and enhancing the efficacy of liposome-based vaccines.
[Show abstract][Hide abstract] ABSTRACT: Liposomes are nanoparticles consisting of phospholipid-bilayer membranes and aqueous compartments. They can effectively incorporate both hydrophobic and hydrophilic molecules, and therefore have been widely applied as a carrier for gene and drug delivery. Moreover, liposomes are considered as a novel vaccine delivery system, which encapsulate both Antigen (Ag) and immunomodulatory agents, facilitating Ag delivery to specific immune cells in vivo. Till date, liposomal vaccines against various diseases, such as cancer, HIV, Hepatitis B and malaria, have been investigated and found to be safe. However, their immunogenicity remains to be further improved. Although conventional liposomes are usually formulated with neutral and/or negatively charged lipids, many studies indicated that the cationic liposomes with positive surface charge more effectively enhanced Ag-specific immune response and promoted vaccine-induced anti-cancer responses than other liposomes. On the other hand, cationic liposomes at a high concentration significantly induced apoptosis of dendritic cells and suppressed immune response, suggesting the immunotoxic effect. In the present study, we incorporated 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), a neutral lipid into dioleoyl-3-trimethylammoniumpropane (DOTAP), a cationic liposome, and investigate the effect of different liposome formulations on monocyte activation and viability. Our aim is to develop a safe and effective liposomal adjuvant for vaccine delivery.