Impact of biopolymer matrices on relaxometric properties of contrast agents

Abstract

Properties of water molecules at the interface between contrast agents (CAs) for magnetic resonance imaging and macromolecules could have a valuable impact on the effectiveness of metal chelates. Recent studies, indeed, demonstrated that polymer architectures could influence CAs' relaxivity by modifying the correlation times of the metal chelate. However, an understanding of the physico-chemical properties of polymer/CA systems is necessary to improve the efficiency of clinically used CAs, still exhibiting low relaxivity. In this context, we investigate the impact of hyaluronic acid (HA) hydrogels on the relaxometric properties of Gd-DTPA, a clinically used CA, to understand better the determining role of the water, which is crucial for both the relaxation enhancement and the polymer conformation. To this aim, water self-diffusion coefficients, thermodynamic interactions and relaxometric properties of HA/Gd-DTPA solutions are studied through time-domain NMR relaxometry and isothermal titration calorimetry. We observed that the presence of Gd-DTPA could alter the polymer conformation and the behaviour of water molecules at the HA/Gd-DTPA interface, thus modulating the relaxivity of the system. In conclusion, the tunability of hydrogel structures could be exploited to improve magnetic properties of metal chelates, inspiring the development of new CAs as well as metallopolymer complexes with applications as sensors and memory devices.

Peptide-functionalized NaGdF4 nanoparticles for tumor-targeted magnetic resonance imaging and effective therapy

“…The relative low r 1 value of NaGdF 4 @bp-peptide NPs may due to the branch structure and rigidity of bp-peptide which prolongs the exchange rate of the intra-spherical water molecules around the Gd 3+ . 60,61 Interactions of NaGdF 4 @bp-peptide NPs with cells…”

Water-Mediated Nanostructures for Enhanced MRI: Impact of Water Dynamics on Relaxometric Properties of Gd-DTPA

“…Among them, the most extensively used CAs in the clinical practice are paramagnetic gadolinium (Gd) chelates 3, 4. Despite their widespread use, these Gd-based CAs are limited by low sensitivity 5, 6; therefore, a large amount of these paramagnetic agents needs to be used to obtain an appropriate diagnostic contrast 7. In many cases, the exposure to Gd-based MRI CAs in patients with compromised renal function is associated with Nephrogenic Systemic Fibrosis (NSF) 8, a systemic disease that can lead to death 9.…”

Confinement of a polymer chain: An entropic study by Monte Carlo method

“…Thermodynamic behavior of the molecules is a relevant topic in a considerable number of applications, from biology to nanomedicine and nanotechnologies; in fact, in these fields, macromolecules are often forced in a reduced volume, smaller than their natural size . The physical behavior exhibited by fluids of small and neutral molecules, confined within porous media, has been exhaustively reviewed in the literature . In the case of macromolecule‐containing systems, the high molecular weight and the possibility for the long chain to experience a number of conformations are additional features that should be taken into account when studying thermodynamics or properties of confined systems.…”