Nanoimmunotherapy, the application of nanotechnology for sustained and targeted delivery of
antigens to dendritic cells (DCs), has attracted much attention in stimulating
antigen-specific immune response for antitumor
therapy. In order to in situ deliver
antigens to DCs for efficient antigen presentation and subsequent induction of strong cytotoxic T lymphocytes (CTL) response, here we developed a multi-
peptide (TRP2180-188 and HGP10025-33) and
toll-like receptor 4 agonist (
monophosphoryl lipid A) codelivery system based on
lipid-coated
zinc phosphate hybrid nanoparticles (LZnP NPs). This delivery system equips with the chelating property of
zinc to realize the high encapsulation efficiency with antigenic
peptides and the influence on immune system with adjuvant-like feature. The combination of H-2K(b) and H-2D(b)-restricted
peptides could provide multiple
epitopes as the target of specific MHC alleles, making
tumor more difficult to escape from the surveillance of immune system. The formulated LZnP
nano-vaccine with the size of 30nm and outer leaflet
lipid exhibited antitumor immunity as the secretion of
cytokines in vitro and increased CD8(+) T cell response from IFN-γ ELISPOT analysis ex vivo. The antitumor effects were further evidenced from the prophylactic, therapeutic and metastatic
melanoma tumor models compared with free
antigens and single
peptide-loaded
nano-vaccines. These results validate the benefit of LZnP-based
vaccine for antitumor immunity and indicate that co-delivery of
tumor antigens along with adjuvant may be an optimized strategy for
tumor immunotherapy.