Enhanced delivery of immunoliposomes to human dendritic cells by targeting the multilectin receptor DEC-205

Abstract Dendritic cells (DC) are specialized white blood cells that initiate and direct immune responses. Targeting DC surface proteins to deliver liposomes carrying antigens has demonstrated potential for eliciting antigen-specific immune responses. To evaluate this strategy in preclinical studies, we prepared anti-human DEC-205 immunoliposomes (anti-hDEC-205 iLPSM) and compared their uptake by monocyte-derived DC (MoDC) and blood DC (BDC) with conventional liposomes (cLPSM). Antibody conjugation increased the number of immature MoDC taking up liposomes to 70–80%, regardless of the antibody coupled, whereas less than 20% endocytosed cLPSM. Anti-hDEC-205-IgG specifically increased cell uptake by 15% and the total iLPSM uptake six-fold. The non-specific iLPSM uptake was unlikely to be Fc receptor-mediated as excess immunoglobulins failed to block the uptake. Only a small population (7–24%) of mature MoDC took up cLPSM and control iLPSM. In contrast, ∼70% of mature MoDC took up anti-hDEC-205 iLPSM, endocytosing 10-fold more iLPSM than the control iLPSM. Anti-hDEC-205 iLPSM uptake by CD1c+ BDC was similar to the immature MoDC, but was five-fold increased compared to the control iLPSM. Confocal microscopy confirmed that the anti-hDEC-205 iLPSM were phagocytosed by DC and available for antigen processing. Thus, DEC-205 is an effective target for delivering liposomes to human DC.