Nano assembly and encapsulation; a versatile platform for slowing the rotation of polyanionic Gd³⁺‐based MRI contrast agents

Abstract

Encapsulating discrete Gd3+ chelates in nano-assembled capsules (NACs) is a simple and effective method of preparing an MRI contrast agent capable of delivering a large payload of high relaxivity imaging agent. The preparation of contrast agent containing NACs had previously focussed preparations incorporating GdDOTP5− into the internal aggregate. In this report we demonstrate that other Gd3+ chelates bearing overall charges as low as 2- can also be used to prepare NACs. This discovery opens up the possibility of using Gd3+ chelates that have inner-sphere water molecules that could further increase the relaxivity enhancement associated with the long τR that arises from encapsulation. However, encapsulation of the q = 1 chelate GdDTPA2− did not give rise to a significant increase in relaxivity relative to encapsulation of the outer-sphere chelate GdTTHA3−. This leads us to the conclusion that in the NAC interior proton transport is not mediated by movement of whole water molecules and the enhanced relaxivity of Gd3+ chelate encapsulated within NACs arises primarily from second sphere effects.

Crosslinked shells for nano-assembled capsules: a new encapsulation method for smaller Gd3+-loaded capsules with exceedingly high relaxivities

“…11, 12 NACs are formed by encapsulating an aggregate of poly-anionic Gd 3+ chelate, such as GdDOTP 5- , and cationic polymer, such as PAH, within a silica nanoparticle (SNP) shell (Fig 1). NACs have substantial advantages over other methods of incorporating large payloads of Gd 3+ chelate into a single structure.…”

“…Because the molecular motion of the Gd 3+ ion is strongly coupled to that of the NAC structure, there is no effective separation of local and global rotation, this lifts the limiting effect of rotation on the per-Gd 3+ relaxivity that can be achieved. 11, 12 …”

“…11, 12 The size of the NACs produced depends on each of these synthetic variables, but most particularly on the charge ratio R . Decreasing the value of R consistently afforded smaller NACs and smaller NACs were found to have higher per-Gd 3+ relaxivities.…”

“…Of the systems investigated thus far the smallest NACs and those with the highest per-Gd 3+ relaxivity were produced by combining the penta-anionic chelate GdDOTP 5- and the cationic polymer polyallylamine hydrochloride (PAH), at R = 0.3 in 3:2 MeCN/H 2 O. 12 These NACs had an average hydrodynamic diameter of 320 nm and a per-Gd 3+ relaxivity of 46.4 s -1 mmolal -1 (20 MHz and 298 K). Although the preparation of Gd 3+ -containing NACs is robust to many synthetic parameters, the SNP encapsulating shell has previously always been preserved.…”

“…Although the preparation of Gd 3+ -containing NACs is robust to many synthetic parameters, the SNP encapsulating shell has previously always been preserved. 11, 12 This despite the fact that a variety of other encapsulating shells have been employed in other nano-assembled capsule applications. 17-19 …”