PMID- 21121669
OWN - NLM
STAT- MEDLINE
DCOM- 20110511
LR  - 20220309
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 8
IP  - 1
DP  - 2011 Feb 7
TI  - Targeting nanosystems to human DCs via Fc receptor as an effective strategy to 
      deliver antigen for immunotherapy.
PG  - 104-16
LID - 10.1021/mp100178k [doi]
AB  - Dendritic cells (DCs) are increasingly being explored as cellular vaccines for 
      tumor immunotherapy, since they provide an effective system of antigen 
      presentation both in vitro and in vivo. An additional advantage of this cell type 
      is that it is possible to target specific antigens through the activation of 
      receptors, such as FcR (the receptor for the IgG Fc fragment) and TLR (toll-like 
      Receptor). Thus, the uptake capacity of DCs can be improved, thereby increasing 
      antigen presentation. This, in turn, would lead to an enhanced immune response, 
      and, in some instances, the tolerance/anergy of immune effector cells present in 
      cancer patients could be reverted. Here we studied various nanotargeting systems, 
      including liposomes and gold nanoparticles of a peptide-based immunotherapeutic 
      vaccine for the treatment of androgen-responsive prostate cancer. Building blocks 
      of the immunogenic peptide consisted of the luteinizing hormone-releasing hormone 
      (LHRH), also known as gonadotropin-releasing hormone (GnRH) peptide (B- and 
      T-cell epitope), in tandem with a T-helper epitope corresponding to the 830-844 
      region of tetanus toxoid. Three new peptides with several modifications at the 
      N-terminal (palmitoyl, acetyl, and FITC) were synthesized. These peptides also 
      contained a Cys as C-terminal residue to facilitate grafting onto gold 
      nanoparticles. To target different antigen formulations to human DCs, the Fc was 
      activated with a cross-linking spacer to generate a free thiol group and thus 
      facilitate conjugation onto gold nanoparticles, liposomes, and peptide. Our 
      results show that gold nanoparticles and liposomes targeted to FcRs of human DCs 
      are effective antigen delivery carriers and induce a strong immune response with 
      respect to nontargeted LHRH-TT-nanoparticle conjugates and a superior response to 
      that of naked antigens. In addition, dual labeling using gold and FITC-peptide 
      allowed DC tracking by flow cytometry as well as transmission electron 
      microscopy. Nanoparticles were observed to show a homogeneous distribution 
      throughout the cytoplasm. These results open up a new approach to the development 
      of a novel strategy for cancer vaccines.
FAU - Cruz, Luis J
AU  - Cruz LJ
AD  - CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, 
      Barcelona Science Park, Barcelona, Spain. jcdomingo@ub.edu
FAU - Rueda, Felix
AU  - Rueda F
FAU - Cordobilla, Begona
AU  - Cordobilla B
FAU - Simon, Lorena
AU  - Simon L
FAU - Hosta, Leticia
AU  - Hosta L
FAU - Albericio, Fernando
AU  - Albericio F
FAU - Domingo, Joan Carles
AU  - Domingo JC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101220
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Antigens)
RN  - 0 (Liposomes)
RN  - 0 (Receptors, Fc)
SB  - IM
MH  - Antigens/*administration & dosage/immunology
MH  - Cells, Cultured
MH  - Chromatography, High Pressure Liquid
MH  - Dendritic Cells/*metabolism
MH  - Flow Cytometry
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Liposomes/metabolism/ultrastructure
MH  - Microscopy, Confocal
MH  - Microscopy, Electron, Transmission
MH  - Nanoparticles/ultrastructure
MH  - Receptors, Fc/*metabolism
EDAT- 2010/12/03 06:00
MHDA- 2011/05/12 06:00
CRDT- 2010/12/03 06:00
PHST- 2010/12/03 06:00 [entrez]
PHST- 2010/12/03 06:00 [pubmed]
PHST- 2011/05/12 06:00 [medline]
AID - 10.1021/mp100178k [doi]
PST - ppublish
SO  - Mol Pharm. 2011 Feb 7;8(1):104-16. doi: 10.1021/mp100178k. Epub 2010 Dec 20.