Recent Advances in Nanovaccines Using Biomimetic Immunomodulatory Materials

Vijayan, Veena; Mohapatra, Adityanarayan; Uthaman, Saji; Park, In-Kyu

e act as a tumor antigen that will trigger the immune response. Yang et al. [52] reported a cancer cell membrane-coated PLGA NP loaded with TLR-7 agonist, imiquimod (R837), and modified with mannose by a surface lipid anchoring method (Figure 7 ). Mannose modification on the surface of the nanovaccine can trigger the antigen-presenting cells uptake and lymph node migration for higher DC maturation. Cancer cell membrane coating performed as a targeting moiety and a cancer-specific antigen. Immune modulatory agent imiquimod (R837) can stimulate the production of cytotoxicity T-cells to kill the cancer cells, and the combined biomimetic vaccines act as an anticancer vaccine by inhibiting cancer cell progression, compared to other controls [52] . Melanoma cancer cell-membrane-coated PLGA NP loaded with CpG oligodeoxynucleotide augmented the anti-tumor immunity and could be used as an antigen/adjuvant vaccination. The cancer cell membrane acted as a tumor antigen and enhanced the immune response. This biomimetic nanovaccine triggered the antigen-presenting cell maturation and proinflammatory cytokines, i.e., interleukin-6 and interleukin-12 (IL-12), by modulating the immune responses to cancer cells [134] . Various types of targeting peptides, nucleic acids, and proteins are introduced during the formulation of biomimetic nanovaccines to activate the immune system. CpG oligonucleotides act as a TLR adjuvant, because its recognition by endosomal TLR9 boosts the immune activities against regulatory T-cells inside cancer patients [22] . Antibodies are found to be more effective at targeting Various types of targeting peptides, nucleic acids, and proteins are introduced during the formulation of biomimetic nanovaccines to activate the immune system. CpG oligonucleotides act as a TLR adjuvant, because its recognition by endosomal TLR9 boosts the immune activities against regulatory T-cells inside cancer patients [22] . Antibodies are found to be more effective at targeting specific antigens and over-expressed receptors on cancer cells for enhanced anticancer therapy [135] . Antibodies, such as anti-PD-1, can inhibit the PD-1/PD-L1 pathway, and block the conversion of the cytotoxic T-cell to the regulatory T-cells. A gas-generating liposome loaded with sodium bicarbonate (NaHCO 3 ) causes more cell death, and releases a high amount of tumor-associated antigens (TAA) [136] . Combined treatment with a gas-generating liposome and anti PD-1 remarkably enhanced the recruitment of immune cells and CTL responses along with the reduction in regulatory T-cells, compared to single treatment of either anti PD-1 or liposome [136] . The VLPs were developed by using noninfectious viral proteins and capsids to target therapeutic agents. VLPs acted as pathogen-associated molecular parents (PAMPs) to induce immune stimulation against cancer. Lizotte et al. reported that the self-assembled VLPs from cowpea mosaic virus served as effective vaccination, and delayed the tumor growth in B16F10 melanoma mice model [137] . VLPs obtained a durable and long-lasting humoral immune response, and were easily adaptable towards pathogenic threats [138] . Patel et al. reported influenza VLPs modified with breast cancer human epidermal growth factor receptor 2 (HER-2) antigen as a potential therapeutic vaccination against HER-2 expressing tumor. VLPs immunization with the HER-2 antigen enhanced the Th1 and Th-2 type antibody responses, and inhibited tumor growth [139] . VLPs deri