Anionic liposomes
The negatively charged lipids mainly include phosphatidylserine (PS), phosphatidylglycerol (PG), phosphatidylinositol (PI), palmitic acid (PA), and so on (Table 1). The liposomes formed or modified by these molecules are called anionic liposomes. Since the APC usually carries a negative charge, an electrostatic repulsion reaction occurs with anionic liposomal. From intuition, the anionic liposome is difficult to promote cellular uptake as an antigen delivery vector. However, in fact, the PS is one of the lipids of the cell membrane. When the anionic liposome of the PS component entered body, a great many specific PS receptors are activated to direct the APC to take the antigen to take place. In a study comparing the activity of lipid adjuvants with different charges, anionic liposomes made from DOPA mixed with OVA antigens could significantly delay the growth of B16-OVA tumors in mice. In the stage of cell culture, the effect of DOPA anionic liposomes on stimulating DC to extract OVA antigen was not as good as that of cationic liposomes, but the intensity of anti-OVA IgG response induced by cationic liposomes was the same, and the mixture of OVA-DOPA liposomes could also induce OVA specific CTL response. Moreover, enzyme linked immunosorbent assay (ELLISA) results showed that DOPA-OVA liposome could significantly up-regulate the expression of MHC II on DC cells and enhance the expression of cytokines IL-6 and CCL-17, which confirmed that both cationic liposomes and anionic liposomes could show strong adjuvant activity [44].
When combined with ID93/GLA (mycobacterial antigen and lipid adjuvant),in vivo experiments showed that anionic liposome (CHO/DPPC/DPPG) produced Th2 cells at the highest rate, which could further promote the immune response of mice [45]. It has been seen that the adjuvant activity of anionic liposomes may activate DC maturation by up-regulating the expression of related genes. It is noteworthy that anionic liposomes are a favorable drug delivery system for mucosal vaccines. The mucus gel layer is negatively charged and is repelled by anionic liposomes. Using an anionic liposome, the progression of particles and the speed of epithelial penetration are accelerated, which is promoted to absorb by M cells through endocytosis [46]. So anionic liposomes are more suitable for oral vaccines, nasal vaccines, and other mucosal vaccines.