Aim: Produce biodegradable nanoparticles to target antigen-presenting cells and evaluate their potential to be used as a vaccine delivery system. Materials & methods: Untargeted PEGylated PLGA-based nanoparticles and mannose-grafted nanoparticles were formulated and physicochemically characterized. Immortalized and primary antigen-presenting cells were used to study nanoparticle internalization patterns. The endocytic pathways and intracellular trafficking followed by nanoparticles were also investigated. Results & discussion: Nanoparticles displayed mannose residues available for binding at the nanoparticle surface. Different nanoparticle internalization patterns by immortalized and primary antigen presenting cells were verified. Macropinocytosis, clathrin-mediated endocytosis, caveolin- and lipid raft-dependent endocytosis are involved in nanoparticles internalization. Nanoparticles demonstrate both endo-lysosomal and cytosolic localizations and a tendency to accumulate nearby the endoplasmic reticulum. Conclusion & future perspective: The developed nanoparticles might drive antigens to be presented through MHC class I and II molecules to both CD8+ and CD4+ T cells, favoring a complete and coordinated immune response. ; Peer reviewed