PMID- 21538973 OWN - NLM STAT- MEDLINE DCOM- 20111103 LR - 20110606 IS - 1520-6033 (Electronic) IS - 1520-6033 (Linking) VI - 27 IP - 3 DP - 2011 May-Jun TI - Recombinant monomeric CD40 ligand for delivering polymer particles to dendritic cells. PG - 830-7 LID - 10.1002/btpr.595 [doi] AB - Dendritic cells (DCs) are considered the most efficient antigen-presenting cells and are therefore ideal targets for in vivo delivery of antigen for vaccines. We are investigating the strategy of using CD40 ligand (CD40L) as a targeting moiety because this protein has the potential to not only target DCs, but also stimulate cell maturation, leading to more potent immune responses. We have shown that a recombinant, monomeric CD40 ligand fusion protein conjugated to polystyrene micro- and nanoparticles led to significantly enhanced uptake by DCs in vitro. This enhancement was observed for particles of both sizes and in both a murine DC cell line and primary DCs. The uptake appeared to be specifically mediated by CD40L binding to CD40 expressed on DCs. Enhanced uptake of nanoparticles in draining lymph nodes of mice was not observed, however, 48 hours after subcutaneous injection. These findings suggest that CD40 ligand may be a potentially useful targeting moiety for delivery of particulate vaccines to DCs, and that further optimization of both CD40L and the polymer carriers is necessary to achieve efficacy in vivo. CI - Copyright (c) 2011 American Institute of Chemical Engineers (AIChE). FAU - Palumbo, R Noelle AU - Palumbo RN AD - Dept. of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA. FAU - Nagarajan, Lakshmi AU - Nagarajan L FAU - Wang, Chun AU - Wang C LA - eng GR - R01CA129189/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110502 PL - United States TA - Biotechnol Prog JT - Biotechnology progress JID - 8506292 RN - 0 (Drug Carriers) RN - 0 (Polymers) RN - 0 (Recombinant Proteins) RN - 0 (Vaccines) RN - 147205-72-9 (CD40 Ligand) SB - IM MH - Animals MH - Biological Transport MH - CD40 Ligand/*therapeutic use MH - Cells, Cultured MH - Dendritic Cells/*metabolism MH - *Drug Carriers MH - Drug Delivery Systems/*methods MH - Lymph Nodes/metabolism MH - Mice MH - Particle Size MH - Polymers/*administration & dosage/metabolism MH - Recombinant Proteins MH - Vaccines EDAT- 2011/05/04 06:00 MHDA- 2011/11/04 06:00 CRDT- 2011/05/04 06:00 PHST- 2010/01/29 00:00 [received] PHST- 2010/11/24 00:00 [revised] PHST- 2011/05/04 06:00 [entrez] PHST- 2011/05/04 06:00 [pubmed] PHST- 2011/11/04 06:00 [medline] AID - 10.1002/btpr.595 [doi] PST - ppublish SO - Biotechnol Prog. 2011 May-Jun;27(3):830-7. doi: 10.1002/btpr.595. Epub 2011 May 2.