Aim: The authors aimed to investigate whether nanotechnology-based delivery of antigenic peptides is feasible for efficiently inducing anti-tumor cytotoxic T lymphocyte responses through vaccination. Materials & methods: Three different murine melanoma antigens were entrapped in lipid-coated poly(D,L-lactide-co-glycolide) nanoparticles (NPs) by the double emulsion method. Results: The loading efficiency of hydrophilic peptides was greatly improved when lipids were introduced to formulate lipid-coated NPs. The lipid-coated NPs carrying a single peptide and/or combinations of multiple lipid-coated NPs carrying antigenic peptides were characterized in vitro and in vivo in a C57/BL6 (B6) mouse model. Both the single melanoma antigen peptide-loaded NPs and combinational delivery of lipid-coated NPs carrying different peptides could induce antigen-specific T-cell responses. However, single peptide-loaded NPs failed to significantly delay the growth of subcutaneously inoculated B16 melanoma cells in a prophylactic setting. By contrast, the combinational delivery of lipid-coated NPs carrying different peptides significantly suppressed growth of inoculated B16 melanoma cells.