posted on 2020-03-31, 13:33authored byGilberto Mulas, Gabriele A. Rolla, Carlos F. G. C. Geraldes, Lucas W. E. Starmans, Mauro Botta, Enzo Terreno, Lorenzo Tei
Although nowadays there is a renewed and growing interest in Mn-based
contrast agents, there are only few studies dealing with Mn-based
lipophilic nanoparticles and how they may be optimized as MRI contrast
agents. Three amphiphilic paramagnetic Mn(II) complexes based on derivatives
of EDTA and 1,4-DO2A were used for the preparation of lipidic nanoparticles.
The length and position of the aliphatic chains were found to control
whether either vesicular liposomes, nonvesicular bicelles, or a mixture
of both was produced as well as the size and morphology of phospholipid-based
self-assembling nanoaggregates. These differences determine whether
hydrophilic Gd-based contrast agents or fluorescent dyes can be entrapped
in the aqueous core of the nanoaggregate. Structural characterization
was performed by cryo-TEM. Detailed 1H NMR relaxometric
analyses were carried out on all systems. The effect of entrapping
gadoteridol in the aqueous core (where present) was studied by preparing
diamagnetic amphiphilic Zn(II) analogues. In the case of homogeneous
systems, the data were also fitted to obtain the relaxometric parameters
for comparison with literature data. The results of these studies
demonstrate enhanced relaxivity of the nanoaggregates with respect
to monomeric analogues. This work allowed us to understand how to
control the formation of different types of nanovesicles (liposomes,
bicelles, and micelles), optimize their MRI contrast, and provide
different in vivo biodistribution characteristics.