## 4 Nanodelivery Platform for Vaccine
### Polymeric Nanocarriers  
Polymeric vectors are a class of systems with a large range of sizes (10-1000 nm); they are mainly natural polymers or synthetic polymeric materials loaded with antigens and immune adjuvants by adsorption, coupling, or covalent binding, in which polymers rich in side chains can achieve multifunctional loading, and they target LNs or tumor sites by controlling their size, hydrophobicity/hydrophilicity, and charge [137]. The design concept of these polymeric vectors provides a new idea for in situ tumor vaccine research. A personalized vaccine for the treatment of colorectal cancer based on an oral modality for in situ vaccination has been identified in a new study. Ce6/R837@Lp127 NPs are based on silk fibroin nanomaterials with an immunoassay4 juvant (imiquimod, R837) and a sonosensitizer (chlorin e6, Ce6), coated with Pluronic F127 (p127) and natural lipids to ensure that they can overcome the obstacles of the mucus barrier. It can induce colorectal cancer cell death by sonodynamic therapy, and the generated neoantigens in the presence of R837 promote DC maturation, sustained tumor suppression, and in situ vaccination (Figure 4) [138]. This provides a novel and reliable idea and a means of treating CRC in situ. Figure 4: After oral administration, the nanoparticles stably reach the gastrointestinal site, successfully traverse the mucosal barrier, and aggregate at the tumor site under US irradiation, inducing the ICD of tumor cells, releasing a large number of antigens, and R827 synergizes with the neoantigens. Reprinted with permission from ref. [138]. Copyright 2024 American Chemical Society. Notes: red up arrow means activation or upward adjustment; blue down arrow means decrease; checkmark means what nanoparticles can achieve. Polyethyleneimine (PEI) is a cationic polymer, a synthetic polymeric nanomaterial, widely used for antigen vaccine delivery. Electrostatic self-assembly of PEI-coupled neoantigens with CpG adjuvant into nanocondensates promotes cross-presentation of antigens and neoantigen-specific CD8+ T cell activation, providing a simple and efficient delivery platform for neoantigen vaccines [139]. In addition to nanoparticles, PEI self-assembled with farnesyl thiosalicylic acid to form amphiphilic micelles (FTS-PEI) was able to be more efficient in tumor transfection and mediate neoantigen vaccine vaccination compared to PEI and its derivatives [140]. For the delivery of mRNA, it is necessary to ensure that it can be protected from enzymatic degradation or directly transported to the cytoplasm or lysosome for escape. It has been found that fluorinated compounds with hydrophobic and lipophilic amphiphilic properties can penetrate the lipid bilayer of the cell membrane and the lysosomal membrane [141]. After modification of PEI with fluorinated compounds, the nanovaccine (F-PEI/mRNA) formed by self-assembly with the neoantigen may have the possibility of lysosomal escape for efficient delivery of mRNA. As a result, F-PEI/mRNA was found to induce higher levels of MHC I antigen presentation and robust specific immune responses [142]. [PERSON] et al. made a very attractive proton-driven nanotransformer-based vaccine (NTV) based on the properties of different polymeric materials, where self-assembled spherical nanostructures dissociate and reassemble themselves into nanofibers and nanosheets in acidic medium, disrupting the in vivo membrane to release neoantigens directly into the cytoplasm [67]. Natural materials such as glucans and chitosans have higher safety profiles compared to synthetic polymeric materials. Saccharomyces cerevisiae \(\beta\)-1,3-glucan particles (GPs) coupled with peptides can form a new antigenic vaccine delivery system (GP-Neeantigen) with highly targeted APCs. In addition, this vaccine system is more stable between batches and has a uniform particle size compared to other synthetic nanoparticles.