Anchoring Dipalmitoyl Phosphoethanolamine to Nanoparticles Boosts Cellular Uptake and Fluorine-19 Magnetic Resonance Signal

Magnetic resonance (MR) methods to detect and quantify fluorine (F-19) nuclei provide the opportunity to study the fate of cellular transplants in vivo. Cells are typically labeled with F-19 nanoparticles, introduced into living organisms and tracked by F-19 MR methods. Background-free imaging and quantification of cell numbers are amongst the strengths of F-19 MR-based cell tracking but challenges pertaining to signal sensitivity and cell detection exist. In this study we aimed to overcome these limitations by manipulating the aminophospholipid composition of F-19 nanoparticles in order to promote their uptake by dendritic cells (DCs). As critical components of biological membranes, phosphatidylethanolamines (PE) were studied. Both microscopy and MR spectroscopy methods revealed a striking (at least one order of magnitude) increase in cytoplasmic uptake of F-19 nanoparticles in DCs following enrichment with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE). The impact of enriching F-19 nanoparticles with PE on DC migration was also investigated. By manipulating the nanoparticle composition and as a result the cellular uptake we provide here one way of boosting F-19 signal per cell in order to overcome some of the limitations related to F-19 MR signal sensitivity. The boost in signal is ultimately necessary to detect and track cells in vivo.