The encapsulation rate of liposomes largely depends on the electrostatic
attraction between liposomes and goods, so the surface charge determines
the interaction between liposomes and biological components, immune
cells, and other charged objects biological components, affecting the
loading and release of liposome antigens. The surface charge of the
cationic liposomes is positive, and an anionic matter, such as nucleic
acids, polypeptides, or the like, is attracted by electrostatic action.
Interestingly, the APC is usually negatively charged, easily adhered to
the cationic liposome, thereby accelerating to phagocytosis. In
addition, surface positive charge can extend the vaccine residence time
in the injection site, increasing the antigen presence, extending the
time of stimulating cellular immunity in the body [37]. Studies have
shown that cationic liposomes can stimulate the expression of dendritic
cell (DC) maturity markers CD80 and CD86, and induce the expression of
CD4+ T cells and the immune response of
CD8+ T cells [38]. Hence, cationic liposomes have
intense immunogenicity.
As early as 2011, scientists summarized the applications of cationic
liposomes in the vaccine [39]. Cationic lipids (Table 1) had
adjuvant activity, including dimethyldioctadecyl ammonium (DDA) and
3β-(N-[N’,N’-dimethylaminoethane]- carbamoyl) cholesterol (DC-Chol),
a cholesterol derivative containing tertiary amine group, which induced
Th1/Th2 immune response and antibody response, showing good mucosal
immunity. N,N,N-trimethylammonium (DOTMA) and octadecenoyloxy
(ethyl-2-heptadecenyl-3-hy-droxyethyl) imidazolinium (DOTIM) are
excellent non-viral gene transfection materials, especially for nucleic
acid substances, often in combination with plasmids [39]. Moreover,
1,2-dioleyl-sn-glycero-3-ethylphosphocoline (DOEPC) and
1,2-dioleoyl-3-trimethyl-ammonium-propane (DOTAP) are the most used
cationic lipids in the construction of tumor vaccine delivery vectors,
because they have higher membrane fusion rates and more multidirectional
immunostimulatory effects than other cationic liposomes [40]. Eleni
et al. analyzed the potency of SLP (synthetic long peptides)-loaded
formulation (DOTAP: DOPC, molar ratio 1:1) [41]. The results showed
that the SLP model delivery system could achieve complete cure of two
invasive tumors (TC-1 and B16 melanoma), demonstrating that the cationic
liposome was a good delivery platform for polypeptide-based tumor
vaccine. Among them, E7 liposomes with poly (ibuprofen C) as adjuvant
can cure 75-100% of the large tumors in immunized mice. The delivery of
cGAMP (a STING ligands) by liposome composed of soybean
L-α-phosphatidylcholine (Soy-PC) and DOTAP (100:1, weight ratio)
activated STING more effectively than soluble cGAMP [42]. In tumor
microenvironment, the liposome induced mice and human macrophages (M)
reprogramed from M2-like phenotype to M1-like phenotype, and enhanced
the expression and costimulatory effect of MHC to increase the apoptosis
of tumor cells [42]. Besides, cationic liposomes can also overcome
the shortcomings of polymer material PLGA’s adsorption efficiency for
nucleic acid molecules. The polymer nanoparticles encapsulated by
DC-CHOL form hybrid nanoparticles with a lipid shell, which can absorb
more nucleic acid adjuvants or nucleic acid antigens and enhance cell
adhesion and absorption [43].
However, the advantages of cationic liposomes in attracting anionic
substances may be paradoxical. While stably loading nucleic acid or
polypeptide molecules and giving priority to targeting APC, cationic
liposomes inevitably attracted other anionic components in the blood,
resulting in accumulation and embolism, which is very fatal to patients.
Consequently, the establishment of cationic liposomes should fully
consider this problem, optimize the formulation of liposomes, so that
the amount of surface charge in a safe and effective range.