PMID- 25531245
OWN - NLM
STAT- MEDLINE
DCOM- 20160303
LR  - 20181202
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 12
IP  - 2
DP  - 2015 Feb 2
TI  - Mannosylated polyion complexes for in vivo gene delivery into CD11c(+) dendritic 
      cells.
PG  - 453-62
LID - 10.1021/mp5005492 [doi]
AB  - Dendritic cells (DCs) possess unique abilities in initiating primary immune 
      responses and thus represent prime targets for DNA-based vaccinations. Here, we 
      describe the design and synthesis of mannosylated polyion complexes (PICs) 
      composed of cationic polyethylenimine (PEI) and hydrophilic polyethylene glycol 
      (PEG) segments, and bearing mono- and trivalent mannose as a ligand for targeting 
      mannose receptor (MR/CD206)-positive DCs. Amino-terminated mannose 
      (Man)-containing ligands in mono- and trivalent presentations (Man- and Man3-, 
      respectively) were prepared and conjugated to PEG via an N-hydroxysuccinimide 
      (NHS)-activated terminal. Thiolated PEI was conjugated to the mannosylated PEG 
      via the maleimide (MAL)-activated terminal. The resulting positively charged 
      diblock copolymers bearing mannoses (Man-PEG-b-PEI and Man3-PEG-b-PEI) were 
      self-assembled with DNA to form PICs with lower surface charge than did their PEI 
      building block and mean hydrodynamic diameters in the range of 100-450 nm, 
      depending on the N/P ratio. Man3-PEG-b-PEI demonstrated a 3-4-fold greater 
      transfection efficiency in MR-positive dendritic cell lines (THP-1, DC2.4), 
      relative to Man-PEG-b-PEI, exhibited low cytotoxicity when compared with PEI, and 
      showed low transfection efficiency in nondendritic HeLa cells. In preliminary in 
      vivo experiments, Man-PEG-b-PEI/DNA and Man3-PEG-b-PEI/DNA demonstrated 2-3-fold 
      higher gene delivery efficiency into CD11c(+) DCs collected from inguinal lymph 
      nodes of C57/BL6 mice, when compared to PEI/DNA complexes, as shown by GFP 
      expression measurements, 24 h post subcutaneous injection. The results indicate 
      that the mannosylated PICs are a safe and effective gene delivery system, showing 
      in vivo specificity toward CD11c(+) DCs.
FAU - Raviv, Lior
AU  - Raviv L
AD  - Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, 
       section signThe Shraga Segal Department of Microbiology and Immunology, Faculty of Health 
      Sciences, and double daggerIlse Katz Institute for Nanoscale Science and Technology, 
      Ben-Gurion University of the Negev , Beer-Sheva, 84105, Israel.
FAU - Jaron-Mendelson, Michal
AU  - Jaron-Mendelson M
FAU - David, Ayelet
AU  - David A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150114
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (CD11c Antigen)
RN  - 0 (Polymers)
RN  - 0 (mannose polyethylenimine)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 9002-98-6 (Polyethyleneimine)
RN  - PHA4727WTP (Mannose)
SB  - IM
MH  - Animals
MH  - CD11c Antigen/*genetics
MH  - Cell Line
MH  - Dendritic Cells/*cytology
MH  - *Gene Transfer Techniques
MH  - HeLa Cells
MH  - Humans
MH  - Mannose/chemistry
MH  - Mice
MH  - Polyethylene Glycols/chemistry
MH  - Polyethyleneimine/chemistry
MH  - Polymers/*chemistry
MH  - Transfection/*methods
OTO - NOTNLM
OT  - dendritic cells
OT  - gene delivery system
OT  - mannose receptor
OT  - mannose-receptor ligands
OT  - multivalency
EDAT- 2014/12/23 06:00
MHDA- 2016/03/05 06:00
CRDT- 2014/12/23 06:00
PHST- 2014/12/23 06:00 [entrez]
PHST- 2014/12/23 06:00 [pubmed]
PHST- 2016/03/05 06:00 [medline]
AID - 10.1021/mp5005492 [doi]
PST - ppublish
SO  - Mol Pharm. 2015 Feb 2;12(2):453-62. doi: 10.1021/mp5005492. Epub 2015 Jan 14.