Tat-functionalized near-infrared emissive polymersomes for dendritic cell labeling

Natalie A. Christian, Michael C. Milone, Shraddha S. Ranka, Guizhi Li, Paul R. Frail, Kevin P. Davis, Frank S. Bates, Michael J. Therien, P. Peter Ghoroghchian, Carl H. June, Daniel A. Hammer

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)31-40
Number of pages10
JournalBioconjugate Chemistry
Volume18
Issue number1
DOIs
StatePublished - Jan 2007

Fingerprint Dive into the research topics of 'Tat-functionalized near-infrared emissive polymersomes for dendritic cell labeling'. Together they form a unique fingerprint.

  • Cite this

    Christian, N. A., Milone, M. C., Ranka, S. S., Li, G., Frail, P. R., Davis, K. P., Bates, F. S., Therien, M. J., Ghoroghchian, P. P., June, C. H., & Hammer, D. A. (2007). Tat-functionalized near-infrared emissive polymersomes for dendritic cell labeling. Bioconjugate Chemistry, 18(1), 31-40. https://doi.org/10.1021/bc0601267