Theranostics 2019; 9(6):1809-1824. doi:10.7150/thno.27313 This issue

Research Paper

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

Franca De Sarno1,2*, Alfonso Maria Ponsiglione1,2*, Maria Russo1,2, Anna Maria Grimaldi3, Ernesto Forte3, Paolo Antonio Netti1,2,4, Enza Torino1,2,4 ✉

1. Department of Chemical, Materials Engineering & Industrial Production, University of Naples Federico II, Piazzale Tecchio 80, 80125 Naples, Italy.
2. Center for Advanced Biomaterials for Health Care, CABHC, Istituto Italiano di Tecnologia, IIT@CRIB, Largo Barsanti e Matteucci 53, 80125 Naples, Italy.
3. IRCCS SDN, Via E. Gianturco 113, 80143 Naples, Italy.
4. Interdisciplinary Research Center on Biomaterials, CRIB, Piazzale Tecchio 80, 80125 Naples, Italy.
*Equal Contribution

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
De Sarno F, Ponsiglione AM, Russo M, Grimaldi AM, Forte E, Netti PA, Torino E. Water-Mediated Nanostructures for Enhanced MRI: Impact of Water Dynamics on Relaxometric Properties of Gd-DTPA. Theranostics 2019; 9(6):1809-1824. doi:10.7150/thno.27313. Available from

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Graphic 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.

Keywords: nanoparticles, MRI, hydrogels, hydrodenticity, contrast agents