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].