Tat-functionalized near-infrared emissive polymersomes for dendritic cell labeling.
Journal Article
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.
Full Text
Duke Authors
Cited Authors
- Christian, NA; Milone, MC; Ranka, SS; Li, G; Frail, PR; Davis, KP; Bates, FS; Therien, MJ; Ghoroghchian, PP; June, CH; Hammer, DA
Published Date
- January 1, 2007
Published In
Volume / Issue
- 18 / 1
Start / End Page
- 31 - 40
PubMed ID
- 17226955
Pubmed Central ID
- 17226955
Electronic International Standard Serial Number (EISSN)
- 1520-4812
International Standard Serial Number (ISSN)
- 1043-1802
Digital Object Identifier (DOI)
- 10.1021/bc0601267
Language
- eng