PMID- 21381651
OWN - NLM
STAT- MEDLINE
DCOM- 20110816
LR  - 20210102
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 8
IP  - 2
DP  - 2011 Apr 4
TI  - Multimodal imaging of nanovaccine carriers targeted to human dendritic cells.
PG  - 520-31
LID - 10.1021/mp100356k [doi]
AB  - Dendritic cells (DCs) are key players in the initiation of adaptive immune 
      responses and are currently exploited in immunotherapy against cancer and 
      infectious diseases. The targeted delivery of nanovaccine particles (NPs) to DCs 
      in vivo is a promising strategy to enhance immune responses. Here, targeted 
      nanovaccine carriers were generated that allow multimodal imaging of 
      nanocarrier-DC interactions from the subcellular to the organism level. These 
      carriers were made of biodegradable poly(D,L-lactide-co-glycolide) harboring 
      superparamagnetic iron oxide particles (SPIO) and fluorescently labeled antigen 
      in a single particle. Targeted delivery was facilitated by coating the NPs with 
      antibodies recognizing the DC-specific receptor DC-SIGN. The fluorescent label 
      allowed for rapid analysis and quantification of specific versus nonspecific 
      uptake of targeted NPs by DCs compared to other blood cells. In addition, it 
      showed that part of the encapsulated antigen reached the lysosomal compartment of 
      DCs within 24 h. Moreover, the presence of fluorescent label did not prevent the 
      antigen from being presented to antigen-specific T cells. The incorporated SPIO 
      was applied to track the NPs at subcellular cell organel level using transmission 
      electron microscopy (TEM). NPs were found within endolysosomal compartments, 
      where part of the SPIO was already released within 24 h. Furthermore, part of the 
      NPs seemed to localize within the cytoplasm. Ex vivo loading of DCs with NPs 
      resulted in efficient labeling and detection by MRI and did not abolish cell 
      migration within collagen scaffolds. In conclusion, incorporation of two imaging 
      agents within a single carrier allows tracking of targeted nanovaccines on a 
      subcellular, cellular and possibly organism level, thereby facilitating rational 
      design of in vivo targeted vaccination strategies.
FAU - Cruz, Luis J
AU  - Cruz LJ
AD  - Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, 
      University Medical Centre, Nijmegen, The Netherlands.
FAU - Tacken, Paul J
AU  - Tacken PJ
FAU - Bonetto, Fernando
AU  - Bonetto F
FAU - Buschow, Sonja I
AU  - Buschow SI
FAU - Croes, Huib J
AU  - Croes HJ
FAU - Wijers, Mietske
AU  - Wijers M
FAU - de Vries, I Jolanda
AU  - de Vries IJ
FAU - Figdor, Carl G
AU  - Figdor CG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110316
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (Drug Carriers)
RN  - 0 (Ferric Compounds)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Magnetite Nanoparticles)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Vaccines, Subunit)
RN  - 1K09F3G675 (ferric oxide)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
SB  - IM
MH  - Antigen Presentation
MH  - Blood Cells/immunology
MH  - Cell Adhesion Molecules/*immunology/metabolism
MH  - Dendritic Cells/*immunology/metabolism
MH  - *Drug Carriers
MH  - Ferric Compounds/chemistry
MH  - Flow Cytometry
MH  - Humans
MH  - Lactic Acid/chemistry
MH  - Lectins, C-Type/*immunology/metabolism
MH  - *Magnetic Resonance Imaging
MH  - Magnetite Nanoparticles/*administration & dosage/chemistry/ultrastructure
MH  - Nanotechnology
MH  - Peptide Fragments/immunology
MH  - Polyglycolic Acid/chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Receptors, Cell Surface/*immunology/metabolism
MH  - T-Lymphocytes/immunology
MH  - Vaccines, Subunit/*immunology
EDAT- 2011/03/09 06:00
MHDA- 2011/08/17 06:00
CRDT- 2011/03/09 06:00
PHST- 2011/03/09 06:00 [entrez]
PHST- 2011/03/09 06:00 [pubmed]
PHST- 2011/08/17 06:00 [medline]
AID - 10.1021/mp100356k [doi]
PST - ppublish
SO  - Mol Pharm. 2011 Apr 4;8(2):520-31. doi: 10.1021/mp100356k. Epub 2011 Mar 16.