Water-mediated nanostructures for enhanced MRI: Impact of water dynamics on relaxometric properties of Gd-DTPA

Franca De Sarno, Alfonso Maria Ponsiglione, Maria Russo, Anna Maria Grimaldi, Ernesto Forte, Paolo Antonio Netti, Enza Torino

Research output: Contribution to journalArticle

Abstract

Recently, rational design of a new class of contrast agents (CAs), based on biopolymers (hydrogels), have received considerable attention in Magnetic Resonance Imaging (MRI) diagnostic field. Several strategies have been adopted to improve relaxivity without chemical modification of the commercial CAs, however, understanding the MRI enhancement mechanism remains a challenge. Methods: A multidisciplinary approach is used to highlight the basic principles ruling biopolymer-CA interactions in the perspective of their influence on the relaxometric properties of the CA. Changes in polymer conformation and thermodynamic interactions of CAs and polymers in aqueous solutions are detected by isothermal titration calorimetric (ITC) measurements and later, these interactions are investigated at the molecular level using NMR to better understand the involved phenomena. Water molecular dynamics of these systems is also studied using Differential Scanning Calorimetry (DSC). To observe relaxometric properties variations, we have monitored the MRI enhancement of the examined structures over all the experiments. The study of polymer-CA solutions reveals that thermodynamic interactions between biopolymers and CAs could be used to improve MRI Gd-based CA efficiency. High-Pressure Homogenization is used to obtain nanoparticles. Results: The effect of the hydration of the hydrogel structure on the relaxometric properties, called Hydrodenticity and its application to the nanomedicine field, is exploited. The explanation of this concept takes place through several key aspects underlying biopolymer-CA’s interactions mediated by the water. In addition, Hydrodenticity is applied to develop Gadolinium-based polymer nanovectors with size around 200 nm with improved MRI relaxation time (10-times). Conclusions: The experimental results indicate that the entrapment of metal chelates in hydrogel nanostructures offers a versatile platform for developing different high performing CAs for disease diagnosis.

Original languageEnglish
Pages (from-to)1809-1824
Number of pages16
JournalTheranostics
Volume9
Issue number6
DOIs
Publication statusPublished - Jan 1 2019

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Keywords

  • Contrast agents
  • Hydrodenticity
  • Hydrogels
  • MRI
  • Nanoparticles

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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