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

Bioconjug Chem. 2007 Jan-Feb;18(1):31-40. doi: 10.1021/bc0601267.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Survival
  • Cells, Cultured
  • Cryoelectron Microscopy
  • Dendritic Cells / cytology
  • Dendritic Cells / metabolism*
  • Gene Products, tat / chemistry*
  • Gene Products, tat / genetics
  • Gene Products, tat / metabolism*
  • Humans
  • Lymphocyte Culture Test, Mixed
  • Microscopy, Electron, Transmission
  • Molecular Structure
  • Phenotype
  • Spectroscopy, Near-Infrared
  • Time Factors

Substances

  • Gene Products, tat