## 4 Nanodelivery Platform for Vaccine
### Lipid Nanoparticles (LNPs)
This tumor vaccine promotes Adpgk/CpG presentation to APCs, activates broad-spectrum T cell responses, and eradicates tumors in combination with ICI, and neoantigen Adpgk-based nanodiscs also produce significant immune responses in mouse models [129]. Cationic lipids are another type of lipid nanoparticle with greater space and greater potential for vaccine loading. The cholesterol-modified cationic peptide DP7 (DP7-C) has been shown to act as an immune adjuvant and delivery vehicle to stimulate DC maturation and enhance immune responses to neoantigen pulsed DC vaccines but is unable to load mRNA. However, after using DOTAP liposomes, it was found that mRNAs were successfully piggybacked on liposomes, and the neoantigen vaccine (DOTAP/DP7-C/LL2 neoantigen mRNA complexes) modified with DP7-C significantly improved the transfection efficiency and antitumor effect of introducing mRNAs encoding neoantigens into DCs, and it promoted DC maturation and lymphocyte-specific responses compared to DOTAP liposomes [83]. Cationic lipids contain ionizable (cationic) head groups. These form stable complexes with negatively charged and hydrophilic nucleic acids, and after endocytosis into the cell, intracellular anionic lipids neutralize the carrier charge so that the negatively charged nucleic acids are released. Cationic lipids are the most extensively used nonviral system for the delivery of nucleic acids, but it is worth noting that their effectiveness and toxicity are correlated, with multivalent cationic lipids being more effective but more toxic than the monovalent state, and that side effects may be reduced if they are similar in structure to naturally occurring lipids (e.g., cationic cholesterol) [130]. A negatively charged DNA vaccine encoding a neoantigen (DD-TMG-IL12/CpG) can bind to cationic lipids by electrostatic interaction to form a more stable cationic lipid-nucleic acid complex, reducing nuclease degradation, facilitating systemic delivery of the vaccine, and markedly inhibiting melanoma tumor growth and lung metastasis in mice with less cytotoxicity [79]. Although TSA is an ideal target for direct targeting of cancer cells, the long time required to identify neoantigens and the complexity of the technique makes direct targeting limited. [PERSON] et al. proposed a whole tumor cell lipid nanovaccine targeting LN, \(\alpha\)-melittin-NP, which utilizes melittin properties to directly induce tumor cell death and help the release of whole tumor antigens in situ. The modified melittin reduced the toxicity to erythrocytes while possessing the optimal size for targeting LNs and the activation ability of APCs [131]. LNPs have significant potential in delivering nucleic acids and peptide chains [125; 132], preventing nucleases, avoiding endosomal capture and phagocytosis, and promoting cellular uptake [133]. In addition to cationic lipids, the development of new-generation LNPs like solid lipid nanoparticles [134], immunoliposomes [135], and nanostructured lipid carriers [136] has solved some of the previous liposome's deficiencies: enhanced long-term physical stability, loading capacity, and bioavailability. In addition to the advantages, issues such as the capture efficiency of LNPs in vivo and the actual cost of production need to be further considered.