Paramagnetic Phospholipid-Based Micelles Targeting
VCAM‑1 Receptors for MRI Visualization of Inflammation
Amerigo Pagoto
Rachele Stefania
Francesca Garello
Francesca Arena
Giuseppe Digilio
Silvio Aime
Enzo Terreno
10.1021/acs.bioconjchem.6b00308.s001
https://acs.figshare.com/articles/journal_contribution/Paramagnetic_Phospholipid-Based_Micelles_Targeting_VCAM_1_Receptors_for_MRI_Visualization_of_Inflammation/3473465
Inflammation
is signaled by the overexpression of epitopes on the
vascular endothelium that primarily aim at recruiting immune cells
into the inflamed area. The intravascular localization of these biomarkers
makes them suitable targets for the MRI visualization of inflammation.
Phospholipid-based nanosystems appear excellent candidates in virtue
of their good biocompatibility, ability to deliver a high number of
imaging units at the target site, and for the easy functionalization
with targeting vectors. In this work, phospholipid-based micelles
(hydrodynamic diameter of 20 nm) loaded with the amphiphilic Gd(III)-complex
Gd-DOTAMA(C18)<sub>2</sub> were vectorized with a small peptide able
to specifically bind VCAM-1 receptors. The micelles displayed a high
longitudinal relaxivity (36.4 s<sup>–1</sup>mmol<sub>Gd</sub><sup>–1</sup> at 25 °C and 0.7 T). A <sup>1</sup>H- and <sup>17</sup>O-water relaxometry study indicated that the paramagnetic
complex embedded in the nanoparticles adopted two isomeric conformations,
likely reflecting the well-known square antiprismatic (SAP) and twisted
square antiprismatic (TSAP) configurations typically observed in DOTA-like
lanthanide complexes. Interestingly, the TSAP structure, showing a
much faster exchange rate for the water molecule coordinated to the
metal ion, was the most abundant, thus explaining the high relaxivity
of the micellar agent. The systemic administration of the micelles
into a lipopolysaccharide-induced murine model of acute inflammation
successfully demonstrated the ability of the targeting agents to detect
the diseased area by <i>T</i><sub>1</sub> contrast enhanced
MRI.
2016-06-17 00:00:00
SAP
MRI
Gd
inflammation
ability
relaxivity
micelle
agent
Inflammation
square antiprismatic
T 1 contrast
VCAM
TSAP