Multifunctional liposomes
An effective antigen carrier requires a variety of functions to enable it to release and deliver antigens to APC at a defined location. Multifunctional liposomes were constructed by doping lipid molecules with different response signals in the assembled liposome structure or modifying liposomes with different functional structures. By adding pH-sensitive lipids DOPE (1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine) to the formula, Banu et al. constructed a pH-sensitive liposome co-encapsulating CpG ODN and cGAMP (TLR9 and STING ligands) to release contents in lysosomal acidic environment [51]. And the synergistic innate immune response was induced by increasing the level of type I and type II interferon. Most importantly, the vaccine formula made the established melanoma regression rate up to 70%. Yuta et al. used liposome modified with 3-methylglutarylated hyperbranched poly (glycidol) (MGlu-HPG)-a pH sensitive polymer [52]. At a weakly acidic pH, after the carboxyl matrix is protonated, the nature of the lipid membrane changed from hydrophilic to hydrophobic, so the stability of the lipid membrane was destroyed and the inclusions were released. Furthermore, their study showed that the introduction of more hydrophobic spacing next to the carboxyl group could obtain 10-fold higher dendritic cell uptake than the short-chain carboxyl modified liposome, which greatly improved the uptake of tumor antigens [53].
The purpose of temperature response can be achieved by adding lipids with different Tc or embedding temperature-sensitive materials into liposomes. The results show that the thermosensitive liposomes composed of DPPC enhance the release of goods near the Tc (Fig. 3A). But thermosensitive liposomes are mainly used in tumor thermotherapy [54].