Finding alternatives to gadolinium (Gd)-based contrast agents (CA) with the same or even better paramagnetic properties is crucial to overcome their established toxicity. Herein we describe the synthesis and characterization of entirely organic metal-free paramagnetic macromolecules based on biocompatible oligoethylene glycol dendrimers fully functionalized with 5 and 20 organic radicals (OEG Gn-PROXYL (n = 0, 1) radical dendrimers) with the aim to be used as magnetic resonance imaging (MRI) contrast agents. Conferring high water solubility on such systems is often a concern, especially in large generation dendrimers. Our approach to overcome such an issue in this study is by synthesizing dendrimers with highly water-soluble branches themselves. In this work, we show that the highly water-soluble OEG Gn-PROXYL (n = 0, 1) radical dendrimers obtained showed properties that convert them in good candidates to be studied as contrast agents for MRI applications like diagnosis and follow-up of infectious diseases, among others. Importantly, with the first generation radical dendrimer, a similar r1 relaxivity value (3.4 mM−1s−1) in comparison to gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) used in clinics (3.2 mM−1s−1, r.t. 7T) has been obtained, and it has been shown to not be cytotoxic, avoiding the toxicity risks associated with the unwanted accumulation of Gd in the body.

This research was funded by the Spanish Government (PID2019-105622RB-I00, MAT2016-80826-R, CTQ2017-90596-REDT and Severo Ochoa FUNMAT-FIP-2018 (J.V.) and SAF-2014-60138-R and RTI2018-093831-B-I00 (M.R.), CSIC (intramural 201760E080 project), CIBER BBN (CB06/01/0033, CB06/01/0074 and intramural ORDECA project) and Generalitat de Catalunya (2017-SGR-918 and 2017-SGR-1439). ICMAB acknowledges Spanish MINECO through the Severo Ochoa Centres of Excellence Programme Grant SEV- 2015-0496.

Peer reviewed