Aim MUC-1-peptide (M-1-pep) loaded poly (lactide-co-glycolide) nanoparticles were coated with protamine sulphate (PS), M-1-pep-PS-P-NPs for targeting antigen presenting cells (APCs) to evoke cytokine release. Methods and results M-1-pep-PS-P-NPs were tailored by emulsion-diffusion evaporation method and characterisedin vitrounder a set of rigorous parameters. The average particle size and zeta potential of optimised M-1-pep-PS-P-B-NPs was measured to be 132.21 +/- 30.71 nm and 6.29 +/- 0.71 mV, significantly (p < 0.01) higher than 71.24 +/- 17.76-nm and -43.41 +/- 3.37 mV of M-1-pep-P-NPs. Further, 50-mu g/ml concentration of M-1-pep-PS-P-B-NPs displayed 82.4% cellular uptake in RAW 264.7 cells calculated in setting of fluorescence intensity significantly (p < 0.05) elevated than 63.1% of M-1-pep-P-NPs. Consistent to quantitative results, M-1-pep-PS-P-B-NPs also confirmed advanced cellular uptake (CU) in RAW 264.7 cells in contrast to M-1-pep-P-NPs suppose to be through multiple mechanisms including phagocytosis and clathrin mediated endocytosis. Conclusion M-1-pep-PS-P-B-NPs must be evaluatedin vivothrough inhalation route of administration for antitumor prospective in lung cancer xenograft model.