High Relaxivity with No Coordinated Waters: A Seemingly Paradoxical Behavior of [Gd(DOTP)]5-Embedded in Nanogels

Nanogels (NGs) obtained by electrostatic inter-actions between chitosan and hyaluronic acid and comprisingparamagnetic Gd chelates are gaining increasing attention for theirpotential application in magnetic resonance bioimaging. Herein,the macrocyclic complexes [Gd(DOTP)]5-, lacking metal-boundwater molecules (q= 0), were confined or used as a cross-linker inthis type of NG. Unlike the typical behavior of Gd complexes withq= 0, a remarkable relaxivity value of 78.0 mM-1s-1was measuredat 20 MHz and 298 K, nearly 20 times greater than that found forthe free complex. A careful analysis of the relaxation dataemphasizes the fundamental role of second sphere water moleculeswith strong and long-lived hydrogen bonding interactions with thecomplex. Finally, PEGylated derivatives of nanoparticles were used for thefirstin vivomagnetic resonance imaging study of this typeof NG, revealing a fast renal excretion of paramagnetic complexes after their release from the NGs

Automated summary

In this study, nanogels consisting of chitosan and hyaluronic acid with paramagnetic Gd chelates were prepared through electrostatic interactions. The resulting nanogels exhibited a significantly higher relaxivity compared to the free complexes, with the role of water molecules in hydrogen bonding interactions playing a key role. Additionally, the in vivo magnetic resonance imaging study of the nanogels revealed a rapid renal excretion of the paramagnetic complexes.