Development of functionalized nanoparticles for vaccine delivery to dendritic cells: a mechanistic approach.
AIM
Produce biodegradable nanoparticles to target antigen-presenting cells (APCs) and evaluate their potential to be used as a vaccine delivery system.


MATERIALS & METHODS
Untargeted PEGylated poly(d,l-lactic-co-glycolide)-based nanoparticles and mannose-grafted nanoparticles were formulated and physicochemically characterized. Immortalized and primary APCs 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 APCs were verified. Macropinocytosis, clathrin-mediated endocytosis, caveolin- and lipid raft-dependent endocytosis are involved in nanoparticles internalization. Nanoparticles demonstrate both endolysosomal and cytosolic localizations and a tendency to accumulate nearby the endoplasmic reticulum.


CONCLUSION
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.
['Silva|Joana M|JM|', 'Vandermeulen|Gaëlle|G|', 'Oliveira|Vanessa G|VG|', 'Pinto|Sandra N|SN|', 'Rodrigues|Catarina|C|', 'Salgado|Ana|A|', 'Afonso|Carlos A|CA|', 'Viana|Ana S|AS|', 'Jérôme|Christine|C|', 'Silva|Liana C|LC|', 'Graca|Luis|L|', 'Préat|Véronique|V|', 'Florindo|Helena F|HF|']
D000818:Animals D000938:Antigen-Presenting Cells D063566:Biodegradable Plastics D001854:Bone Marrow Cells D003713:Dendritic Cells D016503:Drug Delivery Systems D006801:Humans D007113:Immunity, Innate D051379:Mice D053758:Nanoparticles D011100:Polyglycolic Acid D014612:Vaccines
nanoparticles dendritic cells vaccine delivery systems PLGA immunotherapy mannose receptor targeting