Riboflavin is an essential
vitamin for cellular metabolism and is highly upregulated in metabolically active cells. Consequently, targeting the
riboflavin carrier protein (RCP) may be a promising strategy for labeling
cancer and activated endothelial cells. Therefore,
Ultrasmall SuperParamagnetic Iron Oxide nanoparticles (
USPIO) were adsorptively coated with the endogenous RCP
ligand flavin mononucleotide (
FMN), which renders them target-specific and fluorescent. The core diameter, surface morphology and surface coverage of the resulting
FMN-coated
USPIO (FLUSPIO) were evaluated using a variety of physico-chemical characterization techniques (TEM, DLS, MRI and fluorescence spectroscopy). The biocompatibility of FLUSPIO was confirmed using three different cell viability assays (
Trypan blue staining, 7-AAD staining and TUNEL). In vitro evaluation of FLUSPIO using MRI and fluorescence microscopy demonstrated high labeling efficiency of
cancer cells (PC-3, DU-145, LnCap) and activated endothelial cells (HUVEC). Competition experiments (using MRI and ICP-MS) with
a 10- and 100-fold excess of free
FMN confirmed RCP-specific uptake of the FLUSPIO by PC-3 cells and HUVEC. Hence, RCP-targeting via
FMN may be an elegant way to render nanoparticles fluorescent and to increase the labeling efficacy of
cancer and activated endothelial cells. This was shown for FLUSPIO, which due to their high T(2)-relaxivity, are favorably suited for MR cell tracking experiments and
cancer detection in vivo.