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.