PMID- 17226955
OWN - NLM
STAT- MEDLINE
DCOM- 20070227
LR  - 20071203
IS  - 1043-1802 (Print)
IS  - 1043-1802 (Linking)
VI  - 18
IP  - 1
DP  - 2007 Jan-Feb
TI  - Tat-functionalized near-infrared emissive polymersomes for dendritic cell 
      labeling.
PG  - 31-40
AB  - Dendritic cells (DCs) play a pivotal role in both immune tolerance and the 
      initiation of immunological responses. The ability to track DCs in vivo is 
      imperative for the development of DC-based cellular therapies and to advance our 
      understanding of DC function and pathophysiology. Here, we conjugate a cell 
      permeable peptide, Tat, to near-infrared (NIR) emissive polymersomes in order to 
      enable efficient intracellular delivery for future DC tracking with these optical 
      probes. NIR imaging allows quantitative, repetitive, in vivo detection of 
      fluorophore-laden cells, at centimeter tissue depths without disturbing cellular 
      function. Flow cytometry and confocal microscopy results indicate that 
      Tat-mediated polymersome delivery to DCs is concentration and time dependent, 
      resulting in punctate intracellular localization. Further, loading cells with Tat 
      NIR emissive polymersomes does not interfere with cytokine-induced DC maturation 
      and has modest effects on DC viability, but has a significant effect on mature 
      DC-induced activation of naive T cells. We observe significant uptake of NIR 
      emissive polymersomes when conjugated to the peptide, with a lower detection 
      limit of 5000 labeled DCs. The extent of polymersome delivery is estimated as 70 
      000 +/- 10 000 vesicles/cell, equivalent to 0.7 +/- 0.1 fmol of NIR fluorophore. 
      Our studies will enable future in vivo tracking of ex vivo labeled DCs by NIR 
      fluorescence based imaging.
FAU - Christian, Natalie A
AU  - Christian NA
AD  - School of Engineering and Applied Science, Department of Bioengineering, Abramson 
      Family Cancer Research Institute, University of Pennsylvania, Philadelphia, 
      Pennsylvania 19104, USA.
FAU - Milone, Michael C
AU  - Milone MC
FAU - Ranka, Shraddha S
AU  - Ranka SS
FAU - Li, Guizhi
AU  - Li G
FAU - Frail, Paul R
AU  - Frail PR
FAU - Davis, Kevin P
AU  - Davis KP
FAU - Bates, Frank S
AU  - Bates FS
FAU - Therien, Michael J
AU  - Therien MJ
FAU - Ghoroghchian, P Peter
AU  - Ghoroghchian PP
FAU - June, Carl H
AU  - June CH
FAU - Hammer, Daniel A
AU  - Hammer DA
LA  - eng
GR  - CA 105008/CA/NCI NIH HHS/United States
GR  - EB003457-01/EB/NIBIB NIH HHS/United States
GR  - R01CA105216/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Bioconjug Chem
JT  - Bioconjugate chemistry
JID - 9010319
RN  - 0 (Gene Products, tat)
SB  - IM
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Cryoelectron Microscopy
MH  - Dendritic Cells/cytology/*metabolism
MH  - Gene Products, tat/*chemistry/genetics/*metabolism
MH  - Humans
MH  - Lymphocyte Culture Test, Mixed
MH  - Microscopy, Electron, Transmission
MH  - Molecular Structure
MH  - Phenotype
MH  - Spectroscopy, Near-Infrared
MH  - Time Factors
EDAT- 2007/01/18 09:00
MHDA- 2007/02/28 09:00
CRDT- 2007/01/18 09:00
PHST- 2007/01/18 09:00 [pubmed]
PHST- 2007/02/28 09:00 [medline]
PHST- 2007/01/18 09:00 [entrez]
AID - 10.1021/bc0601267 [doi]
PST - ppublish
SO  - Bioconjug Chem. 2007 Jan-Feb;18(1):31-40. doi: 10.1021/bc0601267.