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A Synergy of Key Properties Promotes Dendrimer Conjugates as Prospective Ratiometric Bioresponsive MRI Probes.

Research paper by Liam L Connah, Goran G Angelovski

Indexed on: 10 Nov '18Published on: 10 Nov '18Published in: Biomacromolecules



Abstract

Bioresponsive or smart contrast agents (SCAs) sensitive to Ca are of extreme interest in the development of functional magnetic resonance imaging (MRI) techniques as they can aid in tracking neural activity in vivo. To this end, the design of macromolecular systems based on nanoscaffolds such as dendrimers functionalised with multiple MRI contrast agents have been used to conveniently increase the local concentration of paramagnetic MR reporters and slow the diffusion time of the probe, which are favourable in vivo characteristics. Moreover, previous studies with Ca-sensitive dendrimeric MRI probes revealed favourable properties crucial in the development of a ratiometric T/ T-imaging method that provided a higher contrast-to-noise ratio compared to conventional T- or T-weighted imaging protocols. We therefore developed a series of novel dendrimeric MRI probes (DCAs) with differing structural properties and charge distributions. We thoroughly studied their features such as the relaxometric behaviour, size change and examined their electrostatic behaviours prior to and after the addition of Ca. The most active DCA displayed a common increase in r (3.11 mM s to 5.72 mM s) and a remarkable increase in r (7.44 mM s to 34.57 mM s), resulting in a r/ r ratio increase of the factor 2.52, which is greater than what was previously achieved. These changes in r and r were followed with a hydrodynamic diameter increase from 7.1 ± 1.2 to 8.5 ± 0.7 nm upon the addition of Ca, along with a decrease in the negative surface charge of the nanoparticle. Overall our findings indicate that highly responsive DCAs can be developed only through a combination of properties such as a change in hydration and size of the molecule, which come as a consequence of intramolecular structural and electrostatic changes in the particle. In turn, they provide a model for future preparations of responsive DCAs that can be utilized for both T-weighted and ratiometric T/ T-weighted imaging to visualize essential biological processes in a dynamic fashion.