Self-delivering Nanoemulsions for Dual Fluorine-19 MRI and Fluorescence Detection

Abstract

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.