Enhanced delivery of immunoliposomes to human dendritic cells by targeting the multilectin receptor DEC-205.
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, approximately 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.
Badiee
Ali
A
School of Pharmacy, University of Queensland, St. Lucia, Qld 4172, Australia.
Davies
Nigel
N
McDonald
Kylie
K
Radford
Kristen
K
Michiue
Hiroaki
H
Hart
Derek
D
Kato
Masato
M
D000818:Animals; D015703:Antigens, CD / Q000187:drug effects*; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007202:Indicators and Reagents; D037181:Lectins, C-Type / Q000187:drug effects*; D008081:Liposomes; D018613:Microscopy, Confocal; D015778:Minor Histocompatibility Antigens; D009000:Monocytes / Q000378:metabolism; D011817:Rabbits / Q000276:immunology; D011956:Receptors, Cell Surface / Q000187:drug effects*
D015703:Antigens, CD; C093569:DEC-205 receptor; D004337:Drug Carriers; D007074:Immunoglobulin G; D007202:Indicators and Reagents; D037181:Lectins, C-Type; D008081:Liposomes; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface