Tuning the composition of biocompatible Gd nanohydrogels to achieve hypersensitive dual T₁/T₂ MRI contrast agents

Abstract

A series of hydrogel nanoparticles incorporating MRI contrast agents (GdDOTP and MS325) as potential cross-linkers were elaborated by an easy and robust ionotropic gelation process.

Biological effects induced by Gadolinium nanoparticles on Lymphocyte A20 cell line

“…Recently, confinement of GdCAs within in a hydrophilic polymeric nanostructures has allowed to pass a milestone in MRI probes efficiency (6,7).The corresponding objects that combine an important concentration of GdCAs within high-water content nanostructure help to improve the efficacy of commercially available GdCAs by a factor of 10 to 24. These highly hydrophilic NPs also called hydrogels are obtained by ionic gelation (8)(9)(10)(11)(12) between two biocompatible (13) polysaccharides chitosan (CS) and hyaluronic acid (HA) in the presence of sodium tripolyphosphate (TPP) as a cross-linker (6,7) The biocompatibility of the polymers does not presuppose that the corresponding hydrogels are biocompatible and the biocompatibility of the hydrogels incorporating the GdCA of DOTAREM, GdDOTA (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and GdDOTP (DOTP = 1,4,7,10-tetraazacyclododecane-N,N' ,N'' ,N'''-tetrakis(methylenephosphonic acid) is still poorly explored. Biodegradation, biodistribution and toxicity of chitosan were reported by T Kean et al in a recent review (14) In this context, before considering their applica-tions in clinical area, studies regarding nanoparticles toxicity are necessary (15).…”

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

“…(4–8) Although this type of contrast agent undoubtedly has the advantage of higher relaxivity on low detection limits these gains come with drawbacks. These super paramagnetic nanomaterials are generally used as susceptibility ( T 2 *) agents, rather than T 1 -shortening agents, and therefore afford less desirable negative image contrast.…”

“…However, the relaxivity of Gd 3+ -based contrast agents can be improved by only factor of 10 -15 at best. Clearly, if the detection limit of a molecular imaging probe for MRI is to be driven as low as those available for PET then it will be necessary not only to develop high relaxivity Gd 3+ -based contrast agents, but also deliver a high payload of high relaxivity agents (4,5).…”

“…These complications with Gd 3+ -based agents are the reason why many approaches to molecular imaging have focussed on the development of super paramagnetic nanoparticle-based contrast media (4)(5)(6)(7)(8). Although this type of contrast agent undoubtedly has the advantage of higher relaxivity and lower detection limits these gains come with drawbacks.…”

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

“…GdDOTP 5- in aggregates with hydrogels of a similar size without an encapsulating shell has a slightly higher relaxivity. 30 However, aggregates without a robust encapsulation shell are unlikely to be suitable for in vivo use. CACs incubated in solutions of physiologically relevant metals and in solutions in the pH range 3 to 9 exhibited no change in per-Gd 3+ relaxivity, size or CAC morphology (for more details see ESI).…”