Abstract
The development of MRI probes is of interest for labeling antibiotic-resistant fungal infections based on yeast. Our work showed that yeast cells can be labeled with high-spin Fe(III) complexes to produce enhanced T2 water proton relaxation. These Fe(III)-based macrocyclic complexes contained a 1,4,7-triazacyclononane framework, two pendant alcohol groups, and either a non-coordinating ancillary group and a bound water molecule or a third coordinating pendant. The Fe(III) complexes that had an open coordination site associated strongly with Saccharomyces cerevisiae upon incubation, as shown by screening using Z-spectra analysis. The incubation of one Fe(III) complex with either Saccharomyces cerevisiae or Candida albicans yeast led to an interaction with the β-glucan-based cell wall, as shown by the ready retrieval of the complex by the bidentate chelator called maltol. Other conditions, such as a heat shock treatment of the complexes, produced Fe(III) complex uptake that could not be reversed by the addition of maltol. Appending a fluorescence dye to Fe(TOB) led to uptake through secretory pathways, as shown by confocal fluorescence microscopy and by the incomplete retrieval of the Fe(III) complex by the maltol treatment. Yeast cells that were labeled with these Fe(III) complexes displayed enhanced water proton T2 relaxation, both for S. cerevisiae and for yeast and hyphal forms of C. albicans.
Highlights
IntroductionMany applications involve the use of chemical probes for tracking various types of cells
Many applications involve the use of chemical probes for tracking various types of cells.For example, tracking mammalian cells is important for cell therapy approaches, whereas the monitoring of microbes may be useful for studying infections
The experiments with the Fe(III) coordination complexes were conducted on S. cerevisiae and subsequently extended to C. albicans
Summary
Many applications involve the use of chemical probes for tracking various types of cells. Tracking mammalian cells is important for cell therapy approaches, whereas the monitoring of microbes may be useful for studying infections. In certain cell therapy applications, the cells are modified ex vivo and later implanted into the body. Imaging these cells in vivo would provide real-time distribution information and allow for the assessment of the therapeutic cells. Mammalian cells labeled with paramagnetic MRI contrast agents have been employed in preclinical studies [2,4,5,6]. The cell-labeling approach may be extended to image bacterial and fungal pathogens to investigate the onset and progression of infectious diseases. There are several reports of PET (positron emission tomography) probes for the in vivo imaging of bacteria or fluorescent
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