## 4 Nanodelivery Platform for Vaccine
### Bio-Nanocarriers
#### 4.1.2 Protein/Peptide-Based Nanocarriers  
Proteins and peptides have garnered much attention as nanocarriers because they are biocompatible, biodegradable, and easy to functionalize, which can increase the stability of drugs, peptides, and other substances, reduce their degradation rates [111], and improve the immunogenicity of vaccines and their drainage to lymph nodes [91].  
[PERSON]'s team then attempted to optimize vaccine efficacy by fusing peptide epitopes to carrier proteins, which improved effective lymphatic uptake, protected the peptide epitopes from hydrolysis, and was shown by pharmacokinetics to elicit up to 90-fold immunogenicity [112]. [PERSON]'s team fused the TLR5-binding D0/D1 structural domain of bacterial flagellar proteins (\(\alpha\)CD40.Flg CMV) to the \(\alpha\)CD40 antibody gene containing a neoantigen-derived peptide to form antibody-antigen coupler-adjuvant multifunctional antibody constructs capable of targeting DCs to induce specific T cell responses. Flagellar proteins are found in animal studies and clinical trials to induce antitumor [94] and antiviral [113] immune responses.  
Ferritin is a self-assembled protein shell of 24 subunits and an iron core. [PERSON] et al. have proposed to use SpyCatcher-modified ferritin nanoparticles to carry MC38 tumor-derived neoantigens. This NP vaccine was able to rapidly drain into lymph nodes, targeting dendritic cells, efficiently captured by DLN DCs in vivo, and eliciting efficient and specific CTL responses [58].  
The ability of albumin to target tumors as a carrier for vaccines is because albumin can provide a large number of the nutrients needed for rapid cancer cell proliferation, allowingthe presence of receptors on cancer cell surfaces that are capable of binding to albumin. Albumin as an endogenous substance can avoid the insecurity and complexity of some synthetic nanomaterials. Researchers have designed an albumin-binding vaccine (AlbiVax), and albumin/AlbiVax nanocomplexes can be delivered to LNs with high efficiency to induce effective and long-acting T cell responses. The delivery of neoantigen vaccines using albumin/AlbiVax nanocomplexes effectively enhances specific immunity and improves side effects. Combination with checkpoint inhibitors enhanced therapeutic efficacy [114].  
Peptides have high biological activity, and the properties of their structures allow for various chemical modifications and possible targeting, making them promising for vaccine delivery. It was reported that DP7, a cationic hydrophilic novel antimicrobial peptide (AMP), modified with cholesterol has been found to have the dual role of delivery carrier and immunoassayadjuvant [89]. DP7-C can efficiently deliver a wide range of antigenic peptides to more than 75% of the DCs; at the same time, it can induce DC maturation and pro-inflammatory cytokine release through the TLR2-MyD88-NF-kB pathway, which improves antigen presentation efficiency and plays the role of an immune adjuvant. DP7-C/neoantigen-pulsed DC vaccines, consisting of direct incubation of DP7-C with neoantigens, effectively enhanced the antitumor efficacy of DC vaccination while promoting the MoDC uptake and presentation in advanced lung cancer patients.  
DP7-C has also been validated to deliver microRNA involved in the remodeling of the tumor microenvironment. Its transfection efficiency and cytotoxicity were more advantageous compared to Lipo2000 and PEI25K [115]. In another study based on DP7, a simple dendrimer polypeptide (KK2 DP7) nanoparticle was designed to improve the targeting of LNs, and in combination with immunosuppressive, it also prevented tumor recurrence [116]. This peptide-based delivery platform is also expected to be further developed for delivering peptide- and nucleic acid-based vaccines, especially for mRNA delivery, as negatively charged mRNAs are susceptible to electrostatic binding with cationic peptides [117].