Self-delivering nanoemulsions for dual fluorine-19 MRI and fluorescence detection.
We report the design, synthesis, and biological testing of highly stable, nontoxic perfluoropolyether (PFPE) nanoemulsions for dual 19F MRI-fluorescence detection. A linear PFPE polymer was covalently conjugated to common fluorescent dyes (FITC, Alexa647 and BODIPy-TR), mixed with pluronic F68 and linear polyethyleneimine (PEI), and emulsified by microfluidization. Prepared nanoemulsions (<200 nm) were readily taken up by both phagocytic and non-phagocytic cells in vitro after a short (approximately 3 h) co-incubation. Following cell administration in vivo, 19F MRI selectively visualizes cell migration. Exemplary in vivo MRI images are presented of T cells labeled with a dual-mode nanoemulsion in a BALB/c mouse. Fluorescence detection enables fluorescent microscopy and FACS analysis of labeled cells, as demonstrated in several immune cell types including Jurkat cells, primary T cells and dendritic cells. The intracellular fluorescence signal is directly proportional to the 19F NMR signal and can be used to calibrate cell loading in vitro.
Janjic
Jelena M
JM
Department of Biological Sciences and Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, 4400 Fifth Ave., Pittsburgh, Pennsylvania 15213, USA.
Srinivas
Mangala
M
Kadayakkara
Deepak K K
DK
Ahrens
Eric T
ET
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D004655:Emulsions / Q000737:chemistry*; D004987:Ethers / Q000737:chemistry; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D005461:Fluorine / Q000737:chemistry*; D005466:Fluorocarbons / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
D003287:Contrast Media; D004655:Emulsions; D004987:Ethers; D005456:Fluorescent Dyes; D005466:Fluorocarbons; D005461:Fluorine